Pervasive Neglect of Sex Differences in Biomedical Research

Females have long been underrepresented in preclinical research and clinical drug trials. Directives by the U.S. National Institutes of Health have increased female participation in research protocols, although analysis of outcomes by sex remains infrequent. The long-held view that traits of female rats and mice are more variable than those of males is discredited, supporting equal representation of both sexes in most studies. Drug pharmacokinetic analysis reveals that, among subjects administered a standard drug dose, women are exposed to higher blood drug concentrations and longer drug elimination times. This contributes to increased adverse drug reactions in women and suggests that women are routinely overmedicated and should be administered lower drug doses than men. The past decade has seen progress in female inclusion, but key subsequent steps such as sex-based analysis and sexspecific drug dosing remain to be implemented

Day Length and Estradiol Affect Same-Sex Affiliative Behavior in the Female Meadow Vole

Non-sexual social bonding between adult mammals remains poorly understood, despite its importance in many species. Female meadow voles are territorial and nest alone in long summer day lengths when circulating estradiol concentrations are high, but cohabit in groups in short winter photoperiods when estradiol secretion is low. The influence of day length and estradiol on same-sex huddling behavior was assessed in adult female pairs housed together in long day lengths (LDs) or short day lengths (SDs) from weaning. The behavior of intact, ovariectomized, and estradiol-treated ovariectomized females from each photoperiod was assessed during 3 hour partner preference tests. Intact SD voles, unlike intact LD voles, spent the majority of the test in proximity to their cage mates. Estradiol treatment of SD voles significantly reduced time spent huddling with the partner. Neither ovariectomy nor estradiol treatment significantly affected the amount of time LD females spent in contact with their partners. Low estradiol availability is therefore a necessary but not sufficient condition for maintenance of high levels of huddling. These results establish that ovarian hormones interact with photoperiod to affect same-sex social behavior

Maternal Photoperiodic History Affects Offspring Development in Syrian Hamsters

During the first 7 weeks of postnatal life, short day lengths inhibit the onset of puberty in many photoperiodic rodents, but not in Syrian hamsters. In this species, timing of puberty and fecundity are independent of the early postnatal photoperiod. Gestational day length affects postnatal reproductive development in several rodents; its role in Syrian hamsters has not been assessed. We tested the hypothesis that cumulative effects of pre- and postnatal short day lengths would restrain gonadal development in male Syrian hamsters. Males with prenatal short day exposure were generated by dams transferred to short day lengths 6 weeks, 3 weeks, and 0 weeks prior to mating. Additional groups were gestated in long day lengths and transferred to short days at birth, at 4 weeks of age, or not transferred (control hamsters). In pups of dams exposed to short day treatment throughout gestation, decreased testis growth was apparent by 3 weeks and persisted through 9 weeks of age, at which time maximum testis size was attained. A subset of males (14%), whose dams had been in short days for 3 to 6 weeks prior to mating displayed pronounced delays in testicular development, similar to those of other photoperiodic rodents. This treatment also increased the percentage of male offspring that underwent little or no gonadal regression postnatally (39%). By 19 weeks of age, males housed in short days completed spontaneous gonadal development. After prolonged long day treatment to break refractoriness, hamsters that initially were classified as nonregressors underwent testicular regression in response to a 2nd sequence of short day lengths. The combined action of prenatal and early postnatal short day lengths diminishes testicular growth of prepubertal Syrian hamsters no later than the 3rd week of postnatal life, albeit to a lesser extent than in other photoperiodic rodents

Enhancement and Suppression of Ultradian and Circadian Rhythms Across the Female Hamster Reproductive Cycle

The impact of ovarian hormones on hamster ultradian rhythms (URs) is unknown. We concurrently monitored URs and circadian rhythms (CRs) of home cage locomotor activity during the estrous cycle, pregnancy, and lactation of Syrian hamsters. URs with a mean period of 4–5 h were evident during the dark phase in more than 90% of females on days 1 and 2 of the estrous cycle but were significantly less prevalent on cycle days 3 and 4. The period of the UR did not vary as a function of estrous cycle stage, but at all stages, the UR period was longer in the dark than the light phase. The UR acrophase occurred significantly earlier on cycle day 4 than on days 1 and 2, and UR robustness and amplitude were reduced on days 3 and 4. Robustness, mesor, and amplitude of CRs were greater during cycle days 3 and 4; timing of the CR acrophase was delayed on day 4 relative to all other cycle days. Effects of the estrous cycle on URs were evident only during the dark phase. The proportion of hamsters displaying dark phase URs increased significantly during early and late gestation and decreased during lactation. Pregnancy significantly increased UR complexity, robustness, and amplitude. The emergence of URs over gestation was paralleled by decrements in the robustness and amplitude of CRs, which also were absent in a significant proportion of dams during lactation but re-emerged at weaning of litters. The changing endocrine profile of the estrous cycle, hormonal dynamics of pregnancy and lactation, and nursing demands placed on dams are each associated with alterations in the expression of ultradian and circadian locomotor rhythms. Diminution of CRs and augmentation of URs may afford greater behavioral flexibility during life stages when interactions with mates and offspring are less predictable

What Patients Want to Know about Imaging Examinations: A Multiinstitutional U.S. Survey in Adult and Pediatric Teaching Hospitals on Patient Preferences for Receiving Information before Radiologic Examinations

Purpose To identify what information patients and parents or caregivers found useful before an imaging examination, from whom they preferred to receive information, and how those preferences related to patient-specific variables including demographics and prior radiologic examinations. Materials and Methods A 24-item survey was distributed at three pediatric and three adult hospitals between January and May 2015. The χ2 or Fisher exact test (categorical variables) and one-way analysis of variance or two-sample t test (continuous variables) were used for comparisons. Multivariate logistic regression was used to determine associations between responses and demographics. Results Of 1742 surveys, 1542 (89%) were returned (381 partial, 1161 completed). Mean respondent age was 46.2 years ± 16.8 (standard deviation), with respondents more frequently female (1025 of 1506, 68%) and Caucasian (1132 of 1504, 75%). Overall, 78% (1117 of 1438) reported receiving information about their examination most commonly from the ordering provider (824 of 1292, 64%), who was also the most preferred source (1005 of 1388, 72%). Scheduled magnetic resonance (MR) imaging or nuclear medicine examinations (P < .001 vs other examination types) and increasing education (P = .008) were associated with higher rates of receiving information. Half of respondents (757 of 1452, 52%) sought information themselves. The highest importance scores for pre-examination information (Likert scale ≥4) was most frequently assigned to information on examination preparation and least frequently assigned to whether an alternative radiation-free examination could be used (74% vs 54%; P < .001). Conclusion Delivery of pre-examination information for radiologic examinations is suboptimal, with half of all patients and caregivers seeking information on their own. Ordering providers are the predominant and preferred source of examination-related information, with respondents placing highest importance on information related to examination preparation

Measuring the 8621 \r{A} Diffuse Interstellar Band in Gaia DR3 RVS Spectra: Obtaining a Clean Catalog by Marginalizing over Stellar Types

Diffuse interstellar bands (DIBs) are broad absorption features associated with interstellar dust and can serve as chemical and kinematic tracers. Conventional measurements of DIBs in stellar spectra are complicated by residuals between observations and best-fit stellar models. To overcome this, we simultaneously model the spectrum as a combination of stellar, dust, and residual components, with full posteriors on the joint distribution of the components. This decomposition is obtained by modeling each component as a draw from a high-dimensional Gaussian distribution in the data-space (the observed spectrum) -- a method we call "Marginalized Analytic Data-space Gaussian Inference for Component Separation" (MADGICS). We use a data-driven prior for the stellar component, which avoids missing stellar features not well-modeled by synthetic spectra. This technique provides statistically rigorous uncertainties and detection thresholds, which are required to work in the low signal-to-noise regime that is commonplace for dusty lines of sight. We reprocess all public Gaia DR3 RVS spectra and present an improved 8621 \r{A} DIB catalog, free of detectable stellar line contamination. We constrain the rest-frame wavelength to $8623.14 \pm 0.087$ \r{A} (vacuum), find no significant evidence for DIBs in the Local Bubble from the $1/6^{\rm{th}}$ of RVS spectra that are public, and show unprecedented correlation with kinematic substructure in Galactic CO maps. We validate the catalog, its reported uncertainties, and biases using synthetic injection tests. We believe MADGICS provides a viable path forward for large-scale spectral line measurements in the presence of complex spectral contamination.Comment: 25 pages, 25 figures, submitted to Ap

Use of Precision Medicine Molecular Profiling of Baseline Tumor Specimen May Not Benefit Outcomes in Children With Relapsed or Refractory Pediatric Sarcomas

Given the poor prognosis of pediatric patients with relapsed or refractory sarcomas, discovery and implementation of innovative approaches and tools to guide therapy are urgent needs. This retrospective pilot study evaluated the impact of relapse and refractory therapies aligned with molecular characterization of biopsies collected at the time of primary diagnosis

Non-universal Soft Parameters in Brane World and the Flavor Problem in Supergravity

We consider gravity mediated supersymmetry (SUSY) breaking in 5D spacetime with two 4D branes B1 and B2 separated in the extra dimension. Using an off-shell 5D supergravity (SUGRA) formalism, we argue that the SUSY breaking scales could be non-universal even at the fundamental scale in a brane world setting, since SUSY breaking effects could be effectively localized. As an application, we suggest a model in which the two light chiral MSSM generations reside on B1, while the third generation is located on B2, and the Higgs multiplets as well as gravity and gauge multiplets reside in the bulk. For SUSY breaking of the order of 10--20 TeV caused by a hidden sector localized at B1, the scalars belonging to the first two generations can become sufficiently heavy to overcome the SUSY flavor problem. SUSY breaking on B2 from a different localized hidden sector gives rise to the third generation soft scalar masses of the order of 1 TeV. Gaugino masses are also of the order of 1 TeV if the size of the extra dimension is $\sim 10^{-16}$ ${\rm GeV}^{-1}$. As in 4D effective supersymmetric theory, an adjustment of TeV scale parameters is needed to realize the 100 GeV electroweak symmetry breaking scale.Comment: 1+22 pages, Version to appear in PRD with additional comments and reference