Her subjects make selfish or pro-social moral choices. Together, these results reveal not only differential neural mechanisms for real and hypothetical moral decisions but also that the nature of real moral decisions can be predicted by dissociable networks within the PFC.Keywords: real moral decision-making; fMRI; amygdala; TPJ; ACCINTRODUCTION Psychology has a long tradition demonstrating a fundamental difference between how people believe they will act and how they actually act in the real world (Milgram, 1963; Higgins, 1987). Recent research (Ajzen et al., 2004; Kang et al., 2011; Teper et al., 2011) has confirmed this intention ehavior discrepancy, AG-221 web revealing that people inaccurately predict their future actions because hypothetical decision-making requires mental simulations that are abbreviated, unrepresentative and decontextualized (Gilbert and Wilson, 2007). This `hypothetical bias’ effect (Kang et al., 2011) has routinely demonstrated that the influence of socio-emotional factors and tangible risk (Wilson et al., 2000) is relatively diluted in hypothetical decisions: not only do hypothetical moral probes lack the tension engendered by competing, real-world emotional choices but also they fail to elicit expectations of consequencesboth of which are endemic to real moral reasoning (Krebs et al., 1997). In fact, research has shown that when real contextual pressures and their associated consequences come into play, people can behave in characteristically immoral ways (Baumgartner et al., 2009; Greene and Paxton, 2009). Although there is also important work examining the neural basis of the opposite behavioral findingaltruistic decision-making (Moll et al., 2006)the neural networks underlying the conflicting motivation of maximizing self-gain at the expense of another are still poorly understood. Studying the neural architecture of this form of moral tension is particularly compelling because monetary incentives to behave immorally are pervasive throughout societypeople frequently cheat on their loved ones, steal from their employers or harm others for monetary gain. Moreover, we reasoned that any behavioral and neural disparities between real and hypothetical moral reasoning will likely have the sharpest focus when two fundamental proscriptionsdo not harm others and do not over-benefit the self at the expense of others (Haidt, 2007)are directly pitted against one another. In other words, we speculated that this prototypical moral conflict would provide an ideal test-bed to examine the behavioral and neural differences between intentions and actions.Received 18 April 2012; Accepted 8 June 2012 Advance Access publication 18 June 2012 Correspondence should be addressed to Oriel FeldmanHall, MRC Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 7EF, UK. E-mail: [email protected], we used a `your pain, my gain’ (PvG) laboratory task (Feldmanhall et al., 2012) to operationalize this core choice between personal advantage and another’s welfare: subjects were probed about their willingness to receive money (up to ?00) by physically harming (via electric stimulations) another subject (Figure 1A). The juxtaposition of these two conflicting motivations requires balancing selfish needs against the get RG7800 notion of `doing the right thing’ (Blair, 2007). We carried out a functional magnetic resonance imaging (fMRI) experiment using the PvG task to first explore if real moral behavior mirrors hypothetical in.Her subjects make selfish or pro-social moral choices. Together, these results reveal not only differential neural mechanisms for real and hypothetical moral decisions but also that the nature of real moral decisions can be predicted by dissociable networks within the PFC.Keywords: real moral decision-making; fMRI; amygdala; TPJ; ACCINTRODUCTION Psychology has a long tradition demonstrating a fundamental difference between how people believe they will act and how they actually act in the real world (Milgram, 1963; Higgins, 1987). Recent research (Ajzen et al., 2004; Kang et al., 2011; Teper et al., 2011) has confirmed this intention ehavior discrepancy, revealing that people inaccurately predict their future actions because hypothetical decision-making requires mental simulations that are abbreviated, unrepresentative and decontextualized (Gilbert and Wilson, 2007). This `hypothetical bias’ effect (Kang et al., 2011) has routinely demonstrated that the influence of socio-emotional factors and tangible risk (Wilson et al., 2000) is relatively diluted in hypothetical decisions: not only do hypothetical moral probes lack the tension engendered by competing, real-world emotional choices but also they fail to elicit expectations of consequencesboth of which are endemic to real moral reasoning (Krebs et al., 1997). In fact, research has shown that when real contextual pressures and their associated consequences come into play, people can behave in characteristically immoral ways (Baumgartner et al., 2009; Greene and Paxton, 2009). Although there is also important work examining the neural basis of the opposite behavioral findingaltruistic decision-making (Moll et al., 2006)the neural networks underlying the conflicting motivation of maximizing self-gain at the expense of another are still poorly understood. Studying the neural architecture of this form of moral tension is particularly compelling because monetary incentives to behave immorally are pervasive throughout societypeople frequently cheat on their loved ones, steal from their employers or harm others for monetary gain. Moreover, we reasoned that any behavioral and neural disparities between real and hypothetical moral reasoning will likely have the sharpest focus when two fundamental proscriptionsdo not harm others and do not over-benefit the self at the expense of others (Haidt, 2007)are directly pitted against one another. In other words, we speculated that this prototypical moral conflict would provide an ideal test-bed to examine the behavioral and neural differences between intentions and actions.Received 18 April 2012; Accepted 8 June 2012 Advance Access publication 18 June 2012 Correspondence should be addressed to Oriel FeldmanHall, MRC Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 7EF, UK. E-mail: [email protected], we used a `your pain, my gain’ (PvG) laboratory task (Feldmanhall et al., 2012) to operationalize this core choice between personal advantage and another’s welfare: subjects were probed about their willingness to receive money (up to ?00) by physically harming (via electric stimulations) another subject (Figure 1A). The juxtaposition of these two conflicting motivations requires balancing selfish needs against the notion of `doing the right thing’ (Blair, 2007). We carried out a functional magnetic resonance imaging (fMRI) experiment using the PvG task to first explore if real moral behavior mirrors hypothetical in.

E home and place him or her with a family member ?has become a highly utilized resource. As with many relatively new constructs and policies, research regarding the efficacy of kinship foster care in MG-132MedChemExpress MG-132 promoting well-being in youth placed in out-of-home care lacks definitive evidence. Many reasons exist for child welfare services to opt to place LY294002 web Children with other family members when removed from the home. It is presumed that this process is less disruptive, as the child is being placed with someone he or she already knows. Furthermore, placement with relatives may facilitate communication and contact with the child’s parents (Berrick, Barth, Needell, 1994; Schwartz, 2008). Children in kinship foster care are often able to remain housed with siblings, which has been cited as both a protective and a stabilizing factor (Barth et al., 2007b). Generally kinship foster care placements are more stable, with more children in these settings experiencing as few as one placement, as opposed to nonkinship foster care in which it is not uncommon for children to have four or more placements (Aarons et al., 2010; Fowler, Toro, Miles, 2009; James, Landsverk,J Soc Serv Res. Author manuscript; available in PMC 2016 February 25.Rufa and FowlerPageSlyman, 2004; Perry, Daly, Kotler, 2012). These factors have been the driving rationale for why children may fare better when placed with kin rather than non-kin. Although research supports the potential of kinship settings to increase stability in placements, findings on the impact of this placement on mental health outcomes are mixed. Some studies imply that kinship foster care has positive effects on youth placed out of the home. In one study, kinship foster caregivers were less likely to report internalizing and externalizing problems in the youth in their care than nonkinship foster caregivers (Hegar Rosenthal, 2009), and another corroborated that those in kinship care exhibited fewer behavioral problems than those in nonkinship care, specifically related to fewer placements (Vanschoonlandt, Vanderfaeillie, Van Holen, De Maeyer, Andries, 2012). Other research supports better mental health functioning in general for youth placed in kinship foster care. Youth in kinship care exhibited a better change in social, emotional, and behavioral outcomes compared to those in non-relative foster care in all cases, even when living with depressed caregivers (Garcia et al., 2015). Keller et al. (2001) found that children placed in kinship foster care were no more likely to exceed clinical cut-offs on competence or problem behavior scales on the Child Behavior Checklist than children in the general population; however, children placed in nonkinship foster care were significantly more likely to score in the clinical range on this measure. While this suggests positive effects of kinship foster care on mental health, other studies find null or negative effects. In contrast to studies showing better outcomes when youth are placed in kinship settings, there is evidence to suggest that kinship youth have greater emotional and behavioral problems compared to both the general population (Dubowitz, Zuravin, Starr, Feigelman, Harrington, 1993) as well as youth in nonkinship foster homes (Cuddeback, 2004). In one study, teachers reported higher behavioral problems in kinship foster youth compared to nonkinship foster youth (Hegar Rosenthal, 2009). Another suggested that 26 of children in kinship foster care reported cl.E home and place him or her with a family member ?has become a highly utilized resource. As with many relatively new constructs and policies, research regarding the efficacy of kinship foster care in promoting well-being in youth placed in out-of-home care lacks definitive evidence. Many reasons exist for child welfare services to opt to place children with other family members when removed from the home. It is presumed that this process is less disruptive, as the child is being placed with someone he or she already knows. Furthermore, placement with relatives may facilitate communication and contact with the child’s parents (Berrick, Barth, Needell, 1994; Schwartz, 2008). Children in kinship foster care are often able to remain housed with siblings, which has been cited as both a protective and a stabilizing factor (Barth et al., 2007b). Generally kinship foster care placements are more stable, with more children in these settings experiencing as few as one placement, as opposed to nonkinship foster care in which it is not uncommon for children to have four or more placements (Aarons et al., 2010; Fowler, Toro, Miles, 2009; James, Landsverk,J Soc Serv Res. Author manuscript; available in PMC 2016 February 25.Rufa and FowlerPageSlyman, 2004; Perry, Daly, Kotler, 2012). These factors have been the driving rationale for why children may fare better when placed with kin rather than non-kin. Although research supports the potential of kinship settings to increase stability in placements, findings on the impact of this placement on mental health outcomes are mixed. Some studies imply that kinship foster care has positive effects on youth placed out of the home. In one study, kinship foster caregivers were less likely to report internalizing and externalizing problems in the youth in their care than nonkinship foster caregivers (Hegar Rosenthal, 2009), and another corroborated that those in kinship care exhibited fewer behavioral problems than those in nonkinship care, specifically related to fewer placements (Vanschoonlandt, Vanderfaeillie, Van Holen, De Maeyer, Andries, 2012). Other research supports better mental health functioning in general for youth placed in kinship foster care. Youth in kinship care exhibited a better change in social, emotional, and behavioral outcomes compared to those in non-relative foster care in all cases, even when living with depressed caregivers (Garcia et al., 2015). Keller et al. (2001) found that children placed in kinship foster care were no more likely to exceed clinical cut-offs on competence or problem behavior scales on the Child Behavior Checklist than children in the general population; however, children placed in nonkinship foster care were significantly more likely to score in the clinical range on this measure. While this suggests positive effects of kinship foster care on mental health, other studies find null or negative effects. In contrast to studies showing better outcomes when youth are placed in kinship settings, there is evidence to suggest that kinship youth have greater emotional and behavioral problems compared to both the general population (Dubowitz, Zuravin, Starr, Feigelman, Harrington, 1993) as well as youth in nonkinship foster homes (Cuddeback, 2004). In one study, teachers reported higher behavioral problems in kinship foster youth compared to nonkinship foster youth (Hegar Rosenthal, 2009). Another suggested that 26 of children in kinship foster care reported cl.

Ds adequately. Assessors had to determine whether assigning a payee would likely ameliorate the negative consequences of substance use. One participant only spent 60 a month on alcohol and received other drugs in exchange for letting people use his apartment. Even though the amount spent on alcohol was small, the Lixisenatide clinical trials participant’s alcohol use resulted in his discharge from methadone treatment, after which he relapsed on heroin and had subsequent drug-related problems. Another participant reported receiving cocaine in return for helping drug dealers “run customers.” This participant had a long history of legal problems, hospitalizations, and social conflict associated with his drug use and was taking a large risk by working for drug dealers. A third participant spent an average of only 10 per month on alcohol but reported that she would occasionally binge drink, resulting in blackouts, hospitalizations, and legal problems. Capability is fluid over time, which can create ambiguities–Two beneficiaries illustrate how financial capability is a fluid construct. Ambiguities arise depending on whether capability is assessed over a period of time or at one moment in time. In one case, a participant reported a significant period of time in the preceding six months during which he did not have enough money for food and, Pyrvinium pamoate manufacturer because he had recently been released from prison, did not have a stable place to live. Subsequently, however, the participant started receiving food stamps and, a few weeks later, was able to find stable living arrangements. Looking at the six month period as a whole, the participant was not meeting basic needs for the majority of the time, but at the time of the interview, the participant’s situation had stabilized and his basic needs were met. Another participant reported stable housing and utilities over the preceding six months, but unstable medications, food and clothing. Her needs were met for the majority of the six-month period but episodic impulsive spending contributed to some financial hardship and unmet needs. Predicting future stability caused ambiguity–For four participants, ambiguities arose over the stability of supports that had helped a participant manage money. In one example, a participant would have failed to meet her basic needs from her Social Security payments but was able to with the intermittent help of her family and in-kind transfers with friends. At the time of the participant interview, the participant reported that she had asked her sister to help manage her affairs. The sister’s intervention was successful. However, because the participant had a history of rejecting help, the assessor felt it was unlikely that the participant would continue to allow her sister to assist, and would continue to managePsychiatr Serv. Author manuscript; available in PMC 2016 March 01.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptLazar et al.Pageher funds poorly. In two other cases, a participant’s mother helped manage the participant’s finances but there was inconsistent control of the funds and uncertainty about whether the beneficiaries would continue receiving help. For a fourth beneficiary, the participant pooled resources with his roommate in a joint bank account. The roommate then paid all the bills. The participant was relatively unaware of his expenses and the assessor had difficulty determining the stability of the roommate arrangement. Discrepancies between sources of data (participant.Ds adequately. Assessors had to determine whether assigning a payee would likely ameliorate the negative consequences of substance use. One participant only spent 60 a month on alcohol and received other drugs in exchange for letting people use his apartment. Even though the amount spent on alcohol was small, the participant’s alcohol use resulted in his discharge from methadone treatment, after which he relapsed on heroin and had subsequent drug-related problems. Another participant reported receiving cocaine in return for helping drug dealers “run customers.” This participant had a long history of legal problems, hospitalizations, and social conflict associated with his drug use and was taking a large risk by working for drug dealers. A third participant spent an average of only 10 per month on alcohol but reported that she would occasionally binge drink, resulting in blackouts, hospitalizations, and legal problems. Capability is fluid over time, which can create ambiguities–Two beneficiaries illustrate how financial capability is a fluid construct. Ambiguities arise depending on whether capability is assessed over a period of time or at one moment in time. In one case, a participant reported a significant period of time in the preceding six months during which he did not have enough money for food and, because he had recently been released from prison, did not have a stable place to live. Subsequently, however, the participant started receiving food stamps and, a few weeks later, was able to find stable living arrangements. Looking at the six month period as a whole, the participant was not meeting basic needs for the majority of the time, but at the time of the interview, the participant’s situation had stabilized and his basic needs were met. Another participant reported stable housing and utilities over the preceding six months, but unstable medications, food and clothing. Her needs were met for the majority of the six-month period but episodic impulsive spending contributed to some financial hardship and unmet needs. Predicting future stability caused ambiguity–For four participants, ambiguities arose over the stability of supports that had helped a participant manage money. In one example, a participant would have failed to meet her basic needs from her Social Security payments but was able to with the intermittent help of her family and in-kind transfers with friends. At the time of the participant interview, the participant reported that she had asked her sister to help manage her affairs. The sister’s intervention was successful. However, because the participant had a history of rejecting help, the assessor felt it was unlikely that the participant would continue to allow her sister to assist, and would continue to managePsychiatr Serv. Author manuscript; available in PMC 2016 March 01.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptLazar et al.Pageher funds poorly. In two other cases, a participant’s mother helped manage the participant’s finances but there was inconsistent control of the funds and uncertainty about whether the beneficiaries would continue receiving help. For a fourth beneficiary, the participant pooled resources with his roommate in a joint bank account. The roommate then paid all the bills. The participant was relatively unaware of his expenses and the assessor had difficulty determining the stability of the roommate arrangement. Discrepancies between sources of data (participant.

Ed periodic nature when the gene segment distribution is considered. The data presented here make it possible to consider variations in DNA recombination of the TCR loci as a partial function of the wave-mechanical properties of the DNA double helix. These findings strengthen the argument that immune responses, such as following SCT may represent an example of an ordered dynamical system. Authors’ contributions. Ab.A.T. collected the data and did most of the calculations reported in the paper. Am.A.T. developed the idea and wrote the paper, as well as performing some of the calculations. M.R. critically reviewed and edited the manuscript. M.H.M. planned and supervised the TRB sequencing and critically reviewed and edited the manuscript.Competing interests. The authors have no conflicts of interest to disclose. Funding. Funding for the T-cell sequencing was provided by Genzyme,the manufacturers of Thymoglobulin.Acknowledgements. The authors gratefully acknowledge Ms KassiAvent and Ms Jennifer Berrie for technical help in performing the high-throughput TRB DNA sequencing. We thank Dr CindyDesmarais and Dr Catherine Sanders at Adaptive Biotechnology, Seattle, WA, where the TRB sequencing of donor and recipient blood samples was performed.rsif.royalsocietypublishing.org
Notes Rec. (2015) 69, 419?36 doi:10.1098/rsnr.2015.0017 Published online 2 SeptemberJOHN TYNDALL’S RELIGION: A FRAGMENTby GEOFFREY CANTOR*University of Leeds, Leeds LS2 9JT, UKBoth contemporaries and historians have focused on the high-profile 1874 Belfast Address in which John Tyndall was widely perceived as promulgating atheism. Wuningmeisu CMedChemExpress Wuningmeisu C Although some historians have instead interpreted him as a pantheist or an agnostic, it is clear that any such labels do not accurately capture Tyndall’s religious position throughout his life. By contrast, this paper seeks to chart Tyndall’s religious journey from 1840 (when he was in his late teens) to the autumn of 1848 when he commenced his scientific studies at Marburg. Although he had been imbued with his father’s stern conservative Irish Protestantism and opposition to Catholicism, as a youth he seems for a time to have been attracted to Methodism. Later, however, he questioned and rejected his father’s religious views and was increasingly drawn to the more spiritual outlook of Ralph Waldo Emerson and Thomas Carlyle, along with a more radical attitude to politics. Keywords: John Tyndall; Ralph Waldo Emerson; Thomas Carlyle; Protestantism; MethodismAfter his famous–or perhaps infamous–Belfast Address at the annual meeting of the British Association for the Advancement of Science in 1874, John Tyndall was widely charged with expounding the unacceptable doctrine of materialism and thus with promulgating atheism.1 Although many of Tyndall’s contemporaries and some subsequent historians have read the Belfast Address as demonstrating that Tyndall was an atheist, Olmutinib site others have labelled him a pantheist, while others still have portrayed him as an agnostic.2 Despite disagreement over which label applies best to Tyndall, these commentators have all sought the single noun that captures the essential quality of Tyndall’s religious commitments. Yet the recurrent focus on his 1874 Address and on assigning a label to him ignores the question of his own religious journey. His upbringing was neither atheist nor pantheist nor agnostic; instead he was born into a strict Protestant3 household in County Carlow, Ireland, and brought up in the Protestant faith, sha.Ed periodic nature when the gene segment distribution is considered. The data presented here make it possible to consider variations in DNA recombination of the TCR loci as a partial function of the wave-mechanical properties of the DNA double helix. These findings strengthen the argument that immune responses, such as following SCT may represent an example of an ordered dynamical system. Authors’ contributions. Ab.A.T. collected the data and did most of the calculations reported in the paper. Am.A.T. developed the idea and wrote the paper, as well as performing some of the calculations. M.R. critically reviewed and edited the manuscript. M.H.M. planned and supervised the TRB sequencing and critically reviewed and edited the manuscript.Competing interests. The authors have no conflicts of interest to disclose. Funding. Funding for the T-cell sequencing was provided by Genzyme,the manufacturers of Thymoglobulin.Acknowledgements. The authors gratefully acknowledge Ms KassiAvent and Ms Jennifer Berrie for technical help in performing the high-throughput TRB DNA sequencing. We thank Dr CindyDesmarais and Dr Catherine Sanders at Adaptive Biotechnology, Seattle, WA, where the TRB sequencing of donor and recipient blood samples was performed.rsif.royalsocietypublishing.org
Notes Rec. (2015) 69, 419?36 doi:10.1098/rsnr.2015.0017 Published online 2 SeptemberJOHN TYNDALL’S RELIGION: A FRAGMENTby GEOFFREY CANTOR*University of Leeds, Leeds LS2 9JT, UKBoth contemporaries and historians have focused on the high-profile 1874 Belfast Address in which John Tyndall was widely perceived as promulgating atheism. Although some historians have instead interpreted him as a pantheist or an agnostic, it is clear that any such labels do not accurately capture Tyndall’s religious position throughout his life. By contrast, this paper seeks to chart Tyndall’s religious journey from 1840 (when he was in his late teens) to the autumn of 1848 when he commenced his scientific studies at Marburg. Although he had been imbued with his father’s stern conservative Irish Protestantism and opposition to Catholicism, as a youth he seems for a time to have been attracted to Methodism. Later, however, he questioned and rejected his father’s religious views and was increasingly drawn to the more spiritual outlook of Ralph Waldo Emerson and Thomas Carlyle, along with a more radical attitude to politics. Keywords: John Tyndall; Ralph Waldo Emerson; Thomas Carlyle; Protestantism; MethodismAfter his famous–or perhaps infamous–Belfast Address at the annual meeting of the British Association for the Advancement of Science in 1874, John Tyndall was widely charged with expounding the unacceptable doctrine of materialism and thus with promulgating atheism.1 Although many of Tyndall’s contemporaries and some subsequent historians have read the Belfast Address as demonstrating that Tyndall was an atheist, others have labelled him a pantheist, while others still have portrayed him as an agnostic.2 Despite disagreement over which label applies best to Tyndall, these commentators have all sought the single noun that captures the essential quality of Tyndall’s religious commitments. Yet the recurrent focus on his 1874 Address and on assigning a label to him ignores the question of his own religious journey. His upbringing was neither atheist nor pantheist nor agnostic; instead he was born into a strict Protestant3 household in County Carlow, Ireland, and brought up in the Protestant faith, sha.

As the population mean (Loeve, 1977). Stuttered and non-stuttered disfluencies–Our second finding that preschool-age CWS produce significantly more stuttered and non-stuttered disfluencies than CWNS corroborates findings from previous studies (Ambrose Yairi, 1999; Johnson et al., 1959; Yairi Ambrose, 2005). Whereas the frequency of stuttered disfluencies has been commonly used as a talker-group classification criterion, our data suggest that non-stuttered disfluencies could also be employed to augment decisions about talker group classification based on stuttered disfluencies. The finding that preschool-age CWS produce significantlyNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript7Present authors recognize that syllable-level measures of stuttering can be converted to word-level measures of stuttering and vice versa (Yaruss, 2001). However, this issue goes beyond the purpose and scope of the present study. J Commun Disord. Author manuscript; available in PMC 2015 May 01.5-BrdU clinical trials Tumanova et al.Pagemore non-stuttered disfluencies than CWNS and that the number of non-stuttered disfluencies was a significant predictor for talker group classification provides empirical support for the notion that total number of disfluencies may be another augmentative measure useful for distinguishing between children who do and do not stutter (Adams, 1977). One seemingly apparent assumption, whether children are classified according to parental report (e.g., Boey et al., 2007; Johnson et al., 1959) or objective criteria (e.g., Pellowski Conture, 2002), is that the speech disfluencies exhibited by CWS versus those of CWNS are more dimensional (i.e., continuous) than categorical (i.e., non-continuous) in nature. Our data suggests that both talker groups produce instances of stuttered disfluencies as well as speech disfluencies not classified as stuttering. Thus, the disfluency RM-493 manufacturer distributions for the two talker groups overlap to some degree (something earlier discussed and/or recognized by Johnson et al., 1963). This, of course, does not mean that the two groups are identical. Neither does this overlook the fact that some individuals close to the between-group classification criterion will be challenging to classify. However, clinicians and researchers alike must make decisions about who does and who does not stutter when attempting to empirically study or clinically treat such children. One attempt to inform this decision-making process or minimize behavioral overlap between the two talker groups is the establishment of a priori criteria for talker group classification (taking into consideration empirical evidence, as well as parental, caregiver and/or professional perceptions). The present finding that the number of non-stuttered disfluencies significantly predicted talker group classification support the use of that variable as an adjunct to (but certainly not replacement for) the 3 stuttered disfluencies criterion for talker group classification. It should be noted, however, that while minimizing one type of error (e.g., false negatives) this practice may increase the chances of false positives (see Conture, 2001, Fig. 1.1, for further discussion of the issue of false positives and false negatives when classifying children as CWS vs. CWNS). At present, it seems safe to say that there are no absolute, error-free demarcations that perfectly (i.e., 100 of the time) separate the two talker groups. However, as movement toward a more da.As the population mean (Loeve, 1977). Stuttered and non-stuttered disfluencies–Our second finding that preschool-age CWS produce significantly more stuttered and non-stuttered disfluencies than CWNS corroborates findings from previous studies (Ambrose Yairi, 1999; Johnson et al., 1959; Yairi Ambrose, 2005). Whereas the frequency of stuttered disfluencies has been commonly used as a talker-group classification criterion, our data suggest that non-stuttered disfluencies could also be employed to augment decisions about talker group classification based on stuttered disfluencies. The finding that preschool-age CWS produce significantlyNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript7Present authors recognize that syllable-level measures of stuttering can be converted to word-level measures of stuttering and vice versa (Yaruss, 2001). However, this issue goes beyond the purpose and scope of the present study. J Commun Disord. Author manuscript; available in PMC 2015 May 01.Tumanova et al.Pagemore non-stuttered disfluencies than CWNS and that the number of non-stuttered disfluencies was a significant predictor for talker group classification provides empirical support for the notion that total number of disfluencies may be another augmentative measure useful for distinguishing between children who do and do not stutter (Adams, 1977). One seemingly apparent assumption, whether children are classified according to parental report (e.g., Boey et al., 2007; Johnson et al., 1959) or objective criteria (e.g., Pellowski Conture, 2002), is that the speech disfluencies exhibited by CWS versus those of CWNS are more dimensional (i.e., continuous) than categorical (i.e., non-continuous) in nature. Our data suggests that both talker groups produce instances of stuttered disfluencies as well as speech disfluencies not classified as stuttering. Thus, the disfluency distributions for the two talker groups overlap to some degree (something earlier discussed and/or recognized by Johnson et al., 1963). This, of course, does not mean that the two groups are identical. Neither does this overlook the fact that some individuals close to the between-group classification criterion will be challenging to classify. However, clinicians and researchers alike must make decisions about who does and who does not stutter when attempting to empirically study or clinically treat such children. One attempt to inform this decision-making process or minimize behavioral overlap between the two talker groups is the establishment of a priori criteria for talker group classification (taking into consideration empirical evidence, as well as parental, caregiver and/or professional perceptions). The present finding that the number of non-stuttered disfluencies significantly predicted talker group classification support the use of that variable as an adjunct to (but certainly not replacement for) the 3 stuttered disfluencies criterion for talker group classification. It should be noted, however, that while minimizing one type of error (e.g., false negatives) this practice may increase the chances of false positives (see Conture, 2001, Fig. 1.1, for further discussion of the issue of false positives and false negatives when classifying children as CWS vs. CWNS). At present, it seems safe to say that there are no absolute, error-free demarcations that perfectly (i.e., 100 of the time) separate the two talker groups. However, as movement toward a more da.

Perceptions about HIV testing and their access to HIV tests. Formal social control can significantly affect HIV testing uptake. Most relevant are laws and policies that influence individuals’ decisions to be tested (e.g., anonymous testing, case reporting, partner notification) and laws and policies that address the consequences of an HIV-positive test result (e.g., anti-discrimination, access to treatment). HIV-related laws to protect individual privacy and prohibit discrimination against persons living with or affected by HIV addressed purchase HS-173 perceived barriers to testing such as fears about these repercussions.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAIDS Behav. Author manuscript; available in PMC 2011 December 1.Latkin et al.PageThese rights-protective laws encouraged persons at risk to seek testing voluntarily, which, by increasing testing rates, in turn required that resources be allocated for more HIV testing.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptNew Thonzonium (bromide) supplier science and technologies, including the advent of effective treatment and rapid HIV testing technologies as well as research pointing to a disproportionate number of infections attributed to individuals unaware of their HIV positive status,75 lead public health leaders to reformulate the national approach to HIV testing. Relying on individuals to seek HIV testing services proved insufficient to increase the number of identified cases to significantly reduce HIV incidence.78 Consequently, the CDC began to recommend that most adults be routinely tested.94 Because this approach does not require individuals to initiate the testing process, motivational interventions to increase HIV testing may play a lesser role in achieving national HIV testing objectives than increasing access to HIV tests (e.g., efforts to mitigate the effect of competing priorities on provider ability and willingness to offer patients HIV tests and to recruit and train additional testing personnel).79,94,95 From a structural systems perspective it is important to assess how national HIV testing guidelines may lead to unanticipated changes at the macro, meso, and micro levels. It is also important to examine how the reallocation of resources to support increased testing may impact other HIV prevention programs and organizations and to assess whether policy changes alter norms regarding pre- and post-test counseling. One potential unanticipated outcome may be the altering of social interconnectedness through greater serosorting behaviors. Ethical Issues with Structural-level HIV Interventions Although structural interventions make fewer demands on individual resources, the ethical implications of attempting to manipulate structural-level factors to affect individual behavior can be quite serious. As described above, structural forces are broad, external to the individual, and beyond individual control. Structural interventions may leave some individuals pursuing goals that they did not choose with methods that they cannot avoid. Such programs can compromise individual autonomy by burdening or eliminating behavioral options, thereby reducing individual choice. For example, criminal laws that require persons living with HIV to disclose their serostatus to prospective sexual partners effectively preclude infected individuals from legally exercising other options, such as practicing safer sex or engaging in alternatives to penetrative sex.96 The option to allow.Perceptions about HIV testing and their access to HIV tests. Formal social control can significantly affect HIV testing uptake. Most relevant are laws and policies that influence individuals’ decisions to be tested (e.g., anonymous testing, case reporting, partner notification) and laws and policies that address the consequences of an HIV-positive test result (e.g., anti-discrimination, access to treatment). HIV-related laws to protect individual privacy and prohibit discrimination against persons living with or affected by HIV addressed perceived barriers to testing such as fears about these repercussions.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAIDS Behav. Author manuscript; available in PMC 2011 December 1.Latkin et al.PageThese rights-protective laws encouraged persons at risk to seek testing voluntarily, which, by increasing testing rates, in turn required that resources be allocated for more HIV testing.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptNew science and technologies, including the advent of effective treatment and rapid HIV testing technologies as well as research pointing to a disproportionate number of infections attributed to individuals unaware of their HIV positive status,75 lead public health leaders to reformulate the national approach to HIV testing. Relying on individuals to seek HIV testing services proved insufficient to increase the number of identified cases to significantly reduce HIV incidence.78 Consequently, the CDC began to recommend that most adults be routinely tested.94 Because this approach does not require individuals to initiate the testing process, motivational interventions to increase HIV testing may play a lesser role in achieving national HIV testing objectives than increasing access to HIV tests (e.g., efforts to mitigate the effect of competing priorities on provider ability and willingness to offer patients HIV tests and to recruit and train additional testing personnel).79,94,95 From a structural systems perspective it is important to assess how national HIV testing guidelines may lead to unanticipated changes at the macro, meso, and micro levels. It is also important to examine how the reallocation of resources to support increased testing may impact other HIV prevention programs and organizations and to assess whether policy changes alter norms regarding pre- and post-test counseling. One potential unanticipated outcome may be the altering of social interconnectedness through greater serosorting behaviors. Ethical Issues with Structural-level HIV Interventions Although structural interventions make fewer demands on individual resources, the ethical implications of attempting to manipulate structural-level factors to affect individual behavior can be quite serious. As described above, structural forces are broad, external to the individual, and beyond individual control. Structural interventions may leave some individuals pursuing goals that they did not choose with methods that they cannot avoid. Such programs can compromise individual autonomy by burdening or eliminating behavioral options, thereby reducing individual choice. For example, criminal laws that require persons living with HIV to disclose their serostatus to prospective sexual partners effectively preclude infected individuals from legally exercising other options, such as practicing safer sex or engaging in alternatives to penetrative sex.96 The option to allow.

………………………………………………………………………………………………….. 19 Definition of the genus Apanteles sensu stricto …………………………………………… 19 Species formerly described as Apanteles but here excluded from the genus …….. 22 Dolichogenidea hedyleptae (Muesebeck, 1958), comb. n. ……………………….. 22 Dolichogenidea politiventris (Muesebeck, 1958), comb. n. ……………………… 22 Iconella albinervis (Tobias, 1964), stat rev. ………………………………………….. 22 Illidops scutellaris (Muesebeck, 1921), comb. rev………………………………….. 23 Rhygoplitis sanctivincenti (Ashmead, 1900), comb. n. …………………………… 24 ACG species wrongly assigned to Apanteles in the past ………………………………. 25 General comments on the biology and morphology of Apanteles in Mesoamerica ….25 Species groups of Mesoamerican Apanteles ……………………………………………….. 27 Key to the species-groups of Mesoamerican Apanteles ………………………………… 35 adelinamoralesae MLN1117 site species-group …………………………………………………………. 45 adrianachavarriae species-group ……………………………………………………….. 48 adrianaguilarae species-group …………………………………………………………… 50 alejandromorai species-group ……………………………………………………………. 51 anabellecordobae species-group …………………………………………………………. 53 anamarencoae species-group …………………………………………………………….. 55 GLPG0187MedChemExpress GLPG0187 arielopezi species-group …………………………………………………………………… 56 ater species-group …………………………………………………………………………… 56 bernyapui species-group…………………………………………………………………… 58 bienvenidachavarriae species-group ……………………………………………………. 59 calixtomoragai species-group …………………………………………………………….. 59 carlosguadamuzi species-group ………………………………………………………….. 61 carlosrodriguezi species-group …………………………………………………………… 62 carloszunigai species-group ………………………………………………………………. 63 carpatus species-group …………………………………………………………………….. 63 coffeellae species-group ……………………………………………………………………. 64 diatraeae species-group ……………………………………………………………………. 65 dickyui species-group ………………………………………………………………………. 66 erickduartei species-group ………………………………………………………………… 66 glenriverai species-group ………………………………………………………………….. 68 guadaluperodriguezae species-group …………………………………………………… 68 humbertolopezi species-group……………………………………………………………. 69 isidrochaconi species-group ………………………………………………………………………………………………………………………………………. 19 Definition of the genus Apanteles sensu stricto …………………………………………… 19 Species formerly described as Apanteles but here excluded from the genus …….. 22 Dolichogenidea hedyleptae (Muesebeck, 1958), comb. n. ……………………….. 22 Dolichogenidea politiventris (Muesebeck, 1958), comb. n. ……………………… 22 Iconella albinervis (Tobias, 1964), stat rev. ………………………………………….. 22 Illidops scutellaris (Muesebeck, 1921), comb. rev………………………………….. 23 Rhygoplitis sanctivincenti (Ashmead, 1900), comb. n. …………………………… 24 ACG species wrongly assigned to Apanteles in the past ………………………………. 25 General comments on the biology and morphology of Apanteles in Mesoamerica ….25 Species groups of Mesoamerican Apanteles ……………………………………………….. 27 Key to the species-groups of Mesoamerican Apanteles ………………………………… 35 adelinamoralesae species-group …………………………………………………………. 45 adrianachavarriae species-group ……………………………………………………….. 48 adrianaguilarae species-group …………………………………………………………… 50 alejandromorai species-group ……………………………………………………………. 51 anabellecordobae species-group …………………………………………………………. 53 anamarencoae species-group …………………………………………………………….. 55 arielopezi species-group …………………………………………………………………… 56 ater species-group …………………………………………………………………………… 56 bernyapui species-group…………………………………………………………………… 58 bienvenidachavarriae species-group ……………………………………………………. 59 calixtomoragai species-group …………………………………………………………….. 59 carlosguadamuzi species-group ………………………………………………………….. 61 carlosrodriguezi species-group …………………………………………………………… 62 carloszunigai species-group ………………………………………………………………. 63 carpatus species-group …………………………………………………………………….. 63 coffeellae species-group ……………………………………………………………………. 64 diatraeae species-group ……………………………………………………………………. 65 dickyui species-group ………………………………………………………………………. 66 erickduartei species-group ………………………………………………………………… 66 glenriverai species-group ………………………………………………………………….. 68 guadaluperodriguezae species-group …………………………………………………… 68 humbertolopezi species-group……………………………………………………………. 69 isidrochaconi species-group …………………………………..

A scenario wherein kinetic modifications within the family underlie SIS3 site prestin’s change to a molecular motor would be compelling. Interestingly, zebra fish prestin shows a lower-pass frequency response than rat prestin (33).In 2001, Oliver et al. (13) identified the chloride anion as a key element in prestin activation by voltage. They speculated that extrinsic anions serve as prestin’s voltage sensor (17), moving only partially through the membrane. Our observations and those of others over the ensuing years have challenged this concept, and we have suggested that chloride works as an allosteric-like modulator of prestin. These observations are as follows. 1) Monovalent, divalent, and trivalent anions, which support NLC, show no expected changes in z or Qmax (47). 2) A variety of sulfonic anions shift Vh in widely varying magnitudes and directions along the voltage axis (47). 3) The apparent anion affinity changes depending on the state of prestin, with anions being released from prestin upon hyperpolarization, opposite to the extrinsic sensor hypothesis (48). 4) Mutations of charged residues alter z, our best estimate of unitary sensor charge (41). 5) Prestin shows transport properties ((40,41,43); however, see (39,42)). Despite these challenges, the extrinsic voltage-sensor hypothesis is still entertained. For example, Geertsma et al. (49) used their recently determined crystal structure of SLC26Dg, a prokaryotic fumarate transporter, to speculate on how prestin’s extrinsic voltage sensor might work. They reasoned that a switch to an outward-facing state could move a bound anion a small distance within the membrane. Unfortunately, there are no data showing an outward-facing state, only an inward-facing one. Indeed, if prestin did bind chloride but was incapable of reaching the outward-facing state (a defunct transporter), no chloride movements would occur upon voltage perturbation. Furthermore, the fact that the anion-binding pocket is in the center of the protein would mean that if an outward-facing state were achieved with no release of chloride, the monovalent anion would move a very small distance through the electric field of the membrane. However, z, from Boltzmann fits, indicates that the anion moves three-quarters of the distance through the electric field. Unless the electric field is inordinately concentrated only at the binding site, it is difficult to envisage this scenario. The data AZD3759 site presented here clearly indicate that no direct relation between chloride level and Qmax exists, further suggesting that chloride does not serve as an extrinsic voltage sensor for prestin. Nevertheless, our recent work and meno presto model indicate that chloride binding to prestin is fundamental to the activation of this unusual motor. The model and data indicate that a stretched exponential intermediate transition between the chloride binding and the voltage-enabled state imposes lags that are expressed in whole-cell mechanical responses (28). This intermediate transition also accounts for our frequency- and chloride-dependent effects on measures of total charge movement, Qmax. Indeed, based on site-directed mutations of charged residues, we favor intrinsic charges serving as prestin’s voltage sensors (41). Recently, Gorbunov et al. (50), used cysteine accessibility scanning and molecular modeling to suggest structural homology of prestin to UraA. Notably, the crystal structureBiophysical Journal 110, 2551?561, June 7, 2016Santos-Sacchi and Son.A scenario wherein kinetic modifications within the family underlie prestin’s change to a molecular motor would be compelling. Interestingly, zebra fish prestin shows a lower-pass frequency response than rat prestin (33).In 2001, Oliver et al. (13) identified the chloride anion as a key element in prestin activation by voltage. They speculated that extrinsic anions serve as prestin’s voltage sensor (17), moving only partially through the membrane. Our observations and those of others over the ensuing years have challenged this concept, and we have suggested that chloride works as an allosteric-like modulator of prestin. These observations are as follows. 1) Monovalent, divalent, and trivalent anions, which support NLC, show no expected changes in z or Qmax (47). 2) A variety of sulfonic anions shift Vh in widely varying magnitudes and directions along the voltage axis (47). 3) The apparent anion affinity changes depending on the state of prestin, with anions being released from prestin upon hyperpolarization, opposite to the extrinsic sensor hypothesis (48). 4) Mutations of charged residues alter z, our best estimate of unitary sensor charge (41). 5) Prestin shows transport properties ((40,41,43); however, see (39,42)). Despite these challenges, the extrinsic voltage-sensor hypothesis is still entertained. For example, Geertsma et al. (49) used their recently determined crystal structure of SLC26Dg, a prokaryotic fumarate transporter, to speculate on how prestin’s extrinsic voltage sensor might work. They reasoned that a switch to an outward-facing state could move a bound anion a small distance within the membrane. Unfortunately, there are no data showing an outward-facing state, only an inward-facing one. Indeed, if prestin did bind chloride but was incapable of reaching the outward-facing state (a defunct transporter), no chloride movements would occur upon voltage perturbation. Furthermore, the fact that the anion-binding pocket is in the center of the protein would mean that if an outward-facing state were achieved with no release of chloride, the monovalent anion would move a very small distance through the electric field of the membrane. However, z, from Boltzmann fits, indicates that the anion moves three-quarters of the distance through the electric field. Unless the electric field is inordinately concentrated only at the binding site, it is difficult to envisage this scenario. The data presented here clearly indicate that no direct relation between chloride level and Qmax exists, further suggesting that chloride does not serve as an extrinsic voltage sensor for prestin. Nevertheless, our recent work and meno presto model indicate that chloride binding to prestin is fundamental to the activation of this unusual motor. The model and data indicate that a stretched exponential intermediate transition between the chloride binding and the voltage-enabled state imposes lags that are expressed in whole-cell mechanical responses (28). This intermediate transition also accounts for our frequency- and chloride-dependent effects on measures of total charge movement, Qmax. Indeed, based on site-directed mutations of charged residues, we favor intrinsic charges serving as prestin’s voltage sensors (41). Recently, Gorbunov et al. (50), used cysteine accessibility scanning and molecular modeling to suggest structural homology of prestin to UraA. Notably, the crystal structureBiophysical Journal 110, 2551?561, June 7, 2016Santos-Sacchi and Son.

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