Prevalence of hormone prescription and education for cis and trans women by medical trainees

PREVALENCE OF HORMONE PRESCRIPTION AND EDUCATION FOR CIS AND TRANS WOMEN BY MEDICAL TRAINEES AUTHORS Madison Meister, BA Candidate; Emily J Noonan, PhD, MA; Laura A. Weingartner, PhD, MS BACKGROUND Hormone replacement therapy is a common healthcare practice for contraception, hormone control, and menopause treatment. Transgender patients may also take hormones to affirm their gender identity, such as feminizing hormones (estrogen), for transgender women. Studying how trainees discuss hormone risks for both cis and trans women can demonstrate if disparities exist and how we may address them to overcome healthcare barriers. METHODS Fifty videos were analyzed of third-year medical students taking patient histories from standardized patients, including 28 cis women and 22 trans women. Students had previously completed LGBTQ clinical skills training, and patients reported taking estrogen purchased online for acne control (cis) or gender-affirming (trans) purposes. Videos were analyzed for the presence and context of hormone health risk discussion, student knowledge, and whether the student agreed to prescribe hormones. RESULTS Of the 90% (n=43) of students who agreed to prescribe hormones, 47% (n=20) prescribed conditionally. Conditions included: pending lab results, desire to research hormones, or checking with attending physicians. A larger proportion of trans women were prescribed hormones (95% or 21/22) compared to cisgender women (79% or 22/28). While similar proportions of students discussed hormone risks between patient groups, students discussed their knowledge or discomfort prescribing hormones more frequently with trans women (27% or n=6/22) than cis women (18% or n=5/28). DISCUSSION We expected students to prescribe combined estrogen-progestin oral contraception to cis women. These data show students more readily prescribed estrogen for gender-affirming purposes, suggesting that LGBTQ clinical skills interventions may help prepare students to provide gender-affirming care

A Natural Bias for Language Generation Models

After just a few hundred training updates, a standard probabilistic model for language generation has likely not yet learnt many semantic or syntactic rules of natural language, making it difficult to estimate the probability distribution over next tokens. Yet around this point, these models have identified a simple, loss-minimising behaviour: to output the unigram distribution of the target training corpus. The use of such a heuristic raises the question: Can we initialise our models with this behaviour and save precious compute resources and model capacity? Here we show that we can effectively endow standard neural language generation models with a separate module that reflects unigram frequency statistics as prior knowledge, simply by initialising the bias term in a model's final linear layer with the log-unigram distribution. We use neural machine translation as a test bed for this simple technique and observe that it: (i) improves learning efficiency; (ii) achieves better overall performance; and perhaps most importantly (iii) appears to disentangle strong frequency effects by encouraging the model to specialise in non-frequency-related aspects of language.Comment: Main conference paper at ACL 202

Hermetic Cereal Storage in the Bronze Age

The present paper explores the possibility to better understand the function of pits through phytolith and starch analysis. A case study from the Late Bronze Age/Early Iron Age settlement phase of Rotbav in southeastern Transylvania is discussed in detail. It appears that a large storage vessel originally sealed with a bowl was kept in a pit filled with chaff or straw to preserve its contents

Circadian influence on intrusive re-experiencing in trauma survivors’ daily lives

Background: The core clinical feature of posttraumatic stress disorder (PTSD) is recurrent re-experiencing in form of intrusive memories. While a great number of biological processes are regulated by sleep and internal biological clocks, the effect of 24-hour biological cycles, named circadian rhythm, has not been investigated in the context of intrusive memories. Objective: Here we examined effects of time of day on frequency and characteristics of intrusive re-experiencing. Methods: Fifty trauma survivors reported intrusive memories for 7 consecutive days using ecological momentary assessment in their daily life. We investigated (i) time-of-day dependent effects on frequency and distribution of intrusive re-experiencing in the overall sample as well as in PTSD versus non-PTSD and (ii) time-of-day dependent effects on the memory characteristics intrusiveness, vividness, nowness and fear. Results: Intrusive memories showed a curvilinear pattern that peaked at 2pm. Intrusive memories in the PTSD group showed a constant level of intrusive re-experiencing in the afternoon and evening, whereas a descending slope was present in the non-PTSD group. In PTSD, intrusive memories might thus be experienced in a more time-scattered fashion throughout the day, indicating chronodisruption. Intrusion characteristics did not follow this pattern. Conclusion: Although preliminary and based on a small sample size, these findings contribute to a better understanding of the everyday occurrence and characteristics of intrusive memories, and point to the added value of examining time-dependent effects, which can directly inform prevention and intervention science

Circadian influence on intrusive re-experiencing in trauma survivors’ daily lives

Background: The core clinical feature of posttraumatic stress disorder (PTSD) is recurrent re-experiencing in form of intrusive memories. While a great number of biological processes are regulated by sleep and internal biological clocks, the effect of 24-hour biological cycles, named circadian rhythm, has not been investigated in the context of intrusive memories. Objective: Here we examined effects of time of day on frequency and characteristics of intrusive re-experiencing. Methods: Fifty trauma survivors reported intrusive memories for 7 consecutive days using ecological momentary assessment in their daily life. We investigated (i) time-of-day dependent effects on frequency and distribution of intrusive re-experiencing in the overall sample as well as in PTSD versus non-PTSD and (ii) time-of-day dependent effects on the memory characteristics intrusiveness, vividness, nowness and fear. Results: Intrusive memories showed a curvilinear pattern that peaked at 2pm. Intrusive memories in the PTSD group showed a constant level of intrusive re-experiencing in the afternoon and evening, whereas a descending slope was present in the non-PTSD group. In PTSD, intrusive memories might thus be experienced in a more time-scattered fashion throughout the day, indicating chronodisruption. Intrusion characteristics did not follow this pattern. Conclusion: Although preliminary and based on a small sample size, these findings contribute to a better understanding of the everyday occurrence and characteristics of intrusive memories, and point to the added value of examining time-dependent effects, which can directly inform prevention and intervention science. Influencia circadiana en la re-experimentación intrusiva en la vida diaria de los sobrevivientes de trauma Antecedentes: La característica clínica central del trastorno de estrés postraumático (TEPT) es la re-experimentación recurrente en forma de recuerdos intrusivos. Si bien un gran número de procesos biológicos están regulados por el sueño y los relojes biológicos internos, el efecto de los ciclos biológicos de 24 horas, llamado ritmo circadiano, no ha sido investigado en el contexto de los recuerdos intrusivos. Objetivo: Aquí examinamos los efectos de la hora del día sobre la frecuencia y características de la re-experimentación intrusiva. Métodos: Cincuenta sobrevivientes de trauma reportaron recuerdos intrusivos por 7 días consecutivos usando la evaluación ecológica momentánea en su vida diaria. Investigamos (i) los efectos dependientes de la hora del día sobre la frecuencia y distribución de los recuerdos intrusivos en la muestra general, así como en TEPT versus no TEPT y (ii) los efectos dependien- tes de la hora del día sobre las características de la intrusividad de los recuerdos, vividez, momento presente y miedo. Resultados: Los recuerdos intrusivos mostraron un patrón curvilíneo que alcanzaba su punto máximo a las 2 pm. Los recuerdos intrusivos en el grupo con TEPT mostraron un nivel constante de re-experimentación intrusiva en la tarde y la noche, mientras que en el grupo sin TEPT se observó una pendiente descendiente. En el TEPT, los recuerdos intrusivos pueden experimen- tarse en una manera más dispersa en el tiempo a lo largo del día, lo que indica cronodisrupción. Las características de intrusión no siguieron este patrón. Conclusión: Aunque son preliminares y se basan en un tamaño de muestra pequeño, estos hallazgos contribuyen a una mayor comprensión de la ocurrencia cotidiana y las características de los recuerdos intrusivos y apuntan al valor agregado de examinar sus efectos dependientes del tiempo, que pueden informar directamente a la ciencia de la prevención e intervención. 昼夜节律对创伤幸存者日常生活中闯入性再体验的影响 背景: 创伤后应激障碍(PTSD)的核心临床特征是以闯入性记忆的形式反复再体验。虽然大量 的生物过程受睡眠和内部生物钟的调节,尚未在闯入性记忆的背景下研究 24 小时生物周期 (称为昼夜节律)的影响。 目的: 这里我们考查了一天时间对闯入性再体验频率和特征的影响。 方法 : 50 名创伤幸存者在日常生活中使用生态瞬时评估连续 7 天报告了闯入性记忆。我们 研究了 (i)对整个样本以及 PTSD 与非 PTSD 对比组中闯入性再体验的频率和分布的每日时间 依赖影响,以及 (ii) 对记忆特征闯入性、生动性、当下性和恐惧的每日时间依赖影响。 结果: 闯入性记忆呈现出一种在下午 2 点达到峰值的曲线模式。PTSD组的闯入性记忆在下 午和晚上表现出恒定水平的闯入性再体验,而非PTSD组则呈现下降趋势。因此,在 PTSD 组 中,闯入性记忆可能会在一天中以更分散的方式体验,这表明时间中断。闯入特征没有遵循这 种模式。 结论: 虽然是初步研究并且基于小样本量,这些发现有助于更好了解闯入性记忆的日常发生 和特征,并指出考查其时间依赖效应的附加价值,可以直接为预防和干预提供信息科学

Gal-2 increases H3K4me3 and H3K9ac in trophoblasts and preeclampsia

Preeclampsia (PE) is a severe pregnancy disorder with a pathophysiology not yet completely understood and without curative therapy. The histone modifications H3K4me(3) and H3K9ac, as well as galectin-2 (Gal-2), are known to be decreased in PE. To gain a better understanding of the development of PE, the influence of Gal-2 on histone modification in trophoblasts and in syncytialisation was investigated. Immunohistochemical stains of 13 PE and 13 control placentas were correlated, followed by cell culture experiments. An analysis of H3K4me(3) and H3K9ac was conducted, as well as cell fusion staining with E-cadherin and β-catenin—both after incubation with Gal-2. The expression of H3K4me(3) and H3K9ac correlated significantly with the expression of Gal-2. Furthermore, we detected an increase in H3K4me(3) and H3K9ac after the addition of Gal-2 to BeWo/HVT cells. Moreover, there was increased fusion of HVT cells after incubation with Gal-2. Gal-2 is associated with the histone modifications H3K4me(3) and H3K9ac in trophoblasts. Furthermore, syncytialisation increased after incubation with Gal-2. Therefore, we postulate that Gal-2 stimulates syncytialisation, possibly mediated by H3K4me(3) and H3K9ac. Since Gal-2, as well as H3K4me(3) and H3K9ac, are decreased in PE, the induction of Gal-2 might be a promising therapeutic target

Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort.

Purpose Treatment with pembrolizumab, an anti-programmed death-1 antibody, at 10 mg/kg administered once every 2 weeks, displayed durable antitumor activity in programmed death-ligand 1 (PD-L1) -positive recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 trial. Results from the expansion cohort, in which patients with HNSCC, irrespective of biomarker status, received a fixed dose of pembrolizumab at a less frequent dosing schedule, are reported. Patients and Methods Patients with R/M HNSCC, irrespective of PD-L1 or human papillomavirus status, received pembrolizumab 200 mg intravenously once every 3 weeks. Imaging was performed every 8 weeks. Primary end points were overall response rate (ORR) per central imaging vendor (Response Evaluation Criteria in Solid Tumors v1.1) and safety. Secondary end points included progression-free survival, overall survival, and association of response and PD-L1 expression. Patients who received one or more doses of pembrolizumab were included in analyses. Results Of 132 patients enrolled, median age was 60 years (range, 25 to 84 years), 83% were male, and 57% received two or more lines of therapy for R/M disease. ORR was 18% (95% CI, 12 to 26) by central imaging vendor and 20% (95% CI, 13 to 28) by investigator review. Median duration of response was not reached (range, ≥ 2 to ≥ 11 months). Six-month progression-free survival and overall survival rates were 23% and 59%, respectively. By using tumor and immune cells, a statistically significant increase in ORR was observed for PD-L1-positive versus -negative patients (22% v 4%; P = .021). Treatment-related adverse events of any grade and grade ≥ 3 events occurred in 62% and 9% of patients, respectively. Conclusion Fixed-dose pembrolizumab 200 mg administered once every 3 weeks was well tolerated and yielded a clinically meaningful ORR with evidence of durable responses, which supports further development of this regimen in patients with advanced HNSCC

The small RNA expression profile of the developing murine urinary and reproductive systems

AbstractmicroRNAs (miRNAs) are small non-coding RNAs with fundamental roles in the regulation of gene expression. miRNAs assemble with Argonaute (Ago) proteins to miRNA-protein complexes (miRNPs), which interact with distinct binding sites on mRNAs and regulate gene expression. Specific miRNAs are key regulators of tissue and organ development and it has been shown in mammals that miRNAs are also involved in the pathogenesis of many diseases including cancer. Here, we have characterized the miRNA expression profile of the developing murine genitourinary system. Using a computational approach, we have identified several miRNAs that are specific for the analyzed tissues or the developmental stage. Our comprehensive miRNA expression atlas of the developing genitourinary system forms an invaluable basis for further functional in vivo studies

Pharmacological memory modulation to augment trauma-focused psychotherapy for PTSD: a systematic review of randomised controlled trials

Trauma-focused psychotherapy (tf-PT) is the first-line treatment for posttraumatic stress disorder (PTSD). Tf-PT focuses on processing and modulating trauma memories. Not all patients benefit, however, and there is room for improvement of efficacy. Pharmacologically augmenting trauma memory modulation in the context of tf-PT may help optimise treatment outcome. To systematically review effects of pharmacologically augmented memory modulation in the context of tf-PT for PTSD (PROSPERO preregistration ID: CRD42021230623). We conducted a systematic review of randomised controlled trials of psychotherapy treatment for PTSD. We included placebo-controlled studies that augmented at least one treatment session pharmacologically targeting memory extinction or reconsolidation. We calculated post-treatment between group (pharmacological augmentation vs placebo control) effect sizes of PTSD symptom severity. We included 13 RCTs. There was large heterogeneity in augmentation procedure and methodological quality. Four studies showed significantly greater PTSD symptom reduction in the pharmacological augmentation group (propranolol, hydrocortisone, dexamethasone, D-cycloserine) compared to placebo. Seven studies showed no significant effect of pharmacological augmentation compared to placebo (D-cycloserine, rapamycin, mifepristone, propranolol, mifepristone combined with D-cycloserine, methylene blue). Two studies showed significantly smaller PTSD symptom reduction in the pharmacological augmentation group (D-cycloserine, dexamethasone) compared to placebo. Results of pharmacological augmentation were mixed overall and heterogenous for the pharmacological agents tested in more than one study. Additional studies and replications are needed to identify which pharmacological agents work, in which combination and to identify patient groups that benefit most to tailor PTSD treatment