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Treatment options to assist patients to produce a more perceptually feminine voice include voice therapy (VT) and surgeries to elevate pitch such as the Wendler glottoplasty (WG). The Trans Woman Voice Questionnaire (TWVQ) is a validated quality of life measure for trans women's self-reported perceptions of their voice and is frequently administered before and after such interventions. The 30 statements broadly pertain to how feminine a patient feels their voice is, how effortful it is to produce their voice, and how their voice impacts them psychosocially, making it a useful and specific outcome measure when treating trans females for voice concerns. To compare quality of life outcomes between VT and VT with adjunct WG (VT+WG) based on changes in ratings of individual statements on the TWVQ. A retrospective case series of 31 trans female patients treated was completed. A total of 17 patients underwent VT and 14 underwent VT with adjunctive WG. Ratings for each of the 30 TWVQ statements were compared before and after treatment for each group. Wilcoxon rank-sum tests were used to compare rating changes before and after treatment. Spearman rank-order correlation tests were used to assess the association between total TWVQ score and "current voice" rating. WG was associated with statistically significantly improved ratings for every statement on the TWVQ except one. In contrast, VT was associated with statistically significant improvements in 16 of the 30 statements, which largely pertained to patient emotions surrounding their voice rather than physical aspects such as pitch and dysphonia. Furthermore, while both WG+VT and VT improved the "current voice" rating significantly, WG improved the score by nearly 1 unit more. Lastly, we found a positive association between the total TWVQ score and current voice rating, indicating that lower scores were associated with more self-perceived feminine-sounding voices (P < 0.01). Both VT and VT+WG result in improvements in the TWVQ. The specific statements on the TWVQ offer insight into specific quality of life treatment outcomes, with VT associated with improvements in mostly psychosocial aspects of voice production and VT+WG with both psychosocial and physical aspects. [ABSTRACT FROM AUTHOR]

Fatty acid amide hydrolase (FAAH), an intracellular serine hydrolase enzyme, participates in the deactivation of fatty acid ethanolamides such as the endogenous cannabinoid anandamide, the intestinal satiety factor oleoylethanolamide, and the peripheral analgesic and anti-inflammatory factor palmitoylethanolamide. In the present study, we report on the design, synthesis, and structure-activity relationships (SAR) of a novel class of potent, selective, and systemically active inhibitors of FAAH activity, which we have recently shown to exert potent anxiolytic-like effects in rats. These compounds are characterized by a carbamic template substituted with alkyl or aryl groups at their O- and N-termini. Most compounds inhibit FAAH, but not several other serine hydrolases, with potencies that depend on the size and shape of the substituents. Initial SAR investigations suggested that the requirements for optimal potency are a lipophilic N-alkyl substituent (such as n-butyl or cyclohexyl) and a bent O-aryl substituent. Furthermore, the carbamic group is essential for activity. A 3D-QSAR analysis on the alkylcarbamic acid aryl esters showed that the size and shape of the O-aryl moiety are correlated with FAAH inhibitory potency. A CoMSIA model was constructed, indicating that whereas the steric occupation of an area corresponding to the meta position of an O-phenyl ring improves potency, a region of low steric tolerance on the enzyme active site exists corresponding to the para position of the same ring. The bent shape of the O-aryl moieties that best fit the enzyme surface closely resembles the folded conformations observed in the complexes of unsaturated fatty acids with different proteins. URB524 (N-cyclohexylcarbamic acid biphenyl-3-yl ester, 9g) is the most potent compound of the series (IC(50) = 63 nM) and was therefore selected for further optimization.

Fatty acid amide hydrolase (FAAH), an intracellular serine hydrolase enzyme, participates in the deactivation of fatty acid ethanolamides such as the endogenous cannabinoid anandamide, the intestinal satiety factor oleoylethanolamide, and the peripheral analgesic and anti-inflammatory factor palmitoylethanolamide. In the present study, we report on the design, synthesis, and structure-activity relationships (SAR) of a novel class of potent, selective, and systemically active inhibitors of FAAH activity, which we have recently shown to exert potent anxiolytic-like effects in rats. These compounds are characterized by a carbamic template substituted with alkyl or aryl groups at their O- and N-termini. Most compounds inhibit FAAH, but not several other serine hydrolases, with potencies that depend on the size and shape of the substituents. Initial SAR investigations suggested that the requirements for optimal potency are a lipophilic N-alkyl substituent (such as n-butyl or cyclohexyl) and a bent O-aryl substituent. Furthermore, the carbamic group is essential for activity. A 3D-QSAR analysis on the alkylcarbamic acid aryl esters showed that the size and shape of the O-aryl moiety are correlated with FAAH inhibitory potency. A CoMSIA model was constructed, indicating that whereas the steric occupation of an area corresponding to the meta position of an O-phenyl ring improves potency, a region of low steric tolerance on the enzyme active site exists corresponding to the para position of the same ring. The bent shape of the O-aryl moieties that best fit the enzyme surface closely resembles the folded conformations observed in the complexes of unsaturated fatty acids with different proteins. URB524 (N-cyclohexylcarbamic acid biphenyl-3-yl ester, 9g) is the most potent compound of the series (IC(50) = 63 nM) and was therefore selected for further optimization.

Since the early twentieth century the PhD has been the research degree of choice in the UK, but traditional ideas and practices relating to the degree are now being challenged. This paper sketches out the main drivers of change and explores the main challenges confronting doctoral study within the UK. It explains why there is a need for a wholesale revision of assumptions and expectations about what the PhD is, and it charts the genesis and evolution of the PhD in the UK. Key drivers for change include a new emphasis on skills and training, submission rates and quality of supervision, changes in the examination of the thesis, and the introduction of national benchmarking. The paper then explores changes in the PhD as product and as process, and outlines how and why new forms of doctorate are emerging. It asks, rhetorically, whether the changing nature of the doctorate reflects adaptation to changing circumstances in order to survive.

The employment of graduate students on a part-time basis to help with the teaching of undergraduates is growing in the UK and many higher education institutions are confronted with challenges about how best to do this. UK institutions have much to learn from North American experience of appointing graduate teaching assistants (GTAs), and this paper seeks to highlight key lessons by reviewing published literature on the use of GTAs in North America. After sketching out the emerging context in the UK, some important implications of North American experience in the selection and preparation, training, supervision and mentoring of GTAs are explored. The paper also identifies lessons relating to practical issues (including communication and managing conflict), personal issues (including reflective practices, and issues of identity and self-worth) and professional development issues (including GTAs as aspiring academics and the ambiguity of the GTA role).