Firms consider wages, current and expected productivity, as well as firing and hiring costs when firing a worker. Financing constraints distort this intertemporal trade-off, leading firms to ...sub-optimally fire short-tenured workers with high future expected productivity. We provide empirical evidence of this distortion using matched employer-employee data from the Swedish population between 2000 and 2010. We propose a new empirical strategy that uses credit ratings to identify financing constraints and uses exchange rates and trade data to identify demand shocks. Our empirical results identify an important new misallocation effect of financial frictions that operates within firms across different types of workers.
Based on the new 2017 blood pressure guidelines, the prevalence of high blood pressure (BP) among adults has increased from 32% to 46%. Based on new norms and diagnostic thresholds that better align ...with adult definitions, new clinical practice guidelines were also published for children. The American Academy of Pediatrics clinical practice guidelines for the management of elevated BP in children replace the 2004 fourth report from the National Heart, Lung, and Blood Institute.
To assess the consequences of the American Academy of Pediatrics clinical practice guidelines for the management of elevated BP in children on the prevalence and severity of elevated BP among children and to characterize risk factors for children with new-onset hypertension or a worsening in clinical stage ("reclassified upward").
This study applied both sets of guidelines to classify BP in 15 647 generally healthy, low-risk children aged 5 to 18 years from National Health and Nutrition Examination Surveys (from January 1, 1999, to December 31, 2014). In the case-control portion of the study, children whose BP was reclassified upward (cases) were matched for sex, age, and height with controls with normal BP. Anthropometric and laboratory risk factors were compared, and age- and sex-specific z scores for weight, waist circumference, and body mass index were calculated. Blood pressure was measured by auscultation by trained personnel. After the child rested quietly for 5 minutes, 3 to 4 consecutive BP readings were recorded.
Blood pressure percentiles and clinical classification based on either the 2017 American Academy of Pediatrics guidelines or the 2004 National Heart, Lung, and Blood Institute report.
Among the 15 647 children in the study (7799 girls and 7848 boys; mean SD age, 13.4 2.8 years), based on the American Academy of Pediatrics guidelines, the estimated (weighted) population prevalence of elevated BP increased from 11.8% (95% CI, 11.1%-13.0%) to 14.2% (95% CI, 13.4%-15.0%). Overall, 905 of 15 584 children (5.8%) had newly diagnosed hypertension (n = 381) or a worsening in clinical stage (n = 524), which represents a substantial increase in disease burden for the health care system. Children whose BP was reclassified upward were more likely to be overweight or obese, with higher z scores for weight, waist circumference, and body mass index. The prevalence of abnormal laboratory test results was also increased, with adverse lipid profiles and increased hemoglobin A1c levels (prediabetes).
Clustering of cardiovascular risk factors in otherwise healthy US children suggests that those whose BP was reclassified represent a high-risk population whose cardiovascular risk may previously have been underestimated.
Objective To describe patient characteristics at presentation, treatment, and response to treatment in youth with gender dysphoria. Study design A retrospective chart review of 84 youth with a ...diagnosis of gender dysphoria seen at BC Children's Hospital from 1998-2011. Results Of the 84 patients, 45 (54%) identified as female-to-male (FtM), 37 (44%) as male-to-female (MtF), and 2 (2%) as natal males who were undecided. Median age of presentation was 16.9 years (range 11.4-19.8 years) and 16.6 years (range 12.3-22.5 years) for FtM and MtF youth, respectively. Gonadotropin-releasing hormone analog treatment was prescribed in 27 (32%) patients. One FtM patient developed sterile abscesses with leuprolide acetate; he was switched to triptorelin and tolerated this well. Cross-sex hormones were prescribed in 63 of 84 patients (39 FtM vs 24 MtF, P < .02). Median age at initiation of testosterone injections in FtM patients was 17.3 years (range 13.7-19.8 years); median age at initiation of estrogen therapy in MtF patients was 17.9 years (range 13.3-22.3 years). Three patients stopped cross-sex hormones temporarily due to psychiatric comorbidities (2 FtM) and distress over androgenic alopecia (1 FtM). No severe complications were noted in patients treated with testosterone or estrogen. Conclusion Treatment with gonadotropin-releasing hormone analog and/or cross-sex hormones, in collaboration with transgender-competent mental health professionals, is an intervention that appears to be appropriate in carefully selected youth with gender dysphoria. Long-term follow-up studies are needed to determine the safety of these treatments in this age group.
Although emergence of gender dysphoria at puberty is long established, a distinct pathway of rapid onset gender dysphoria was recently hypothesized based on parental data. Using adolescent clinical ...data, we tested a series of associations that would be consistent with this pathway, however, our results did not support the rapid onset gender dysphoria hypothesis.
In adults, anthropometric measures of central adiposity, such as waist-height ratio (WHtR) and waist circumference (WC), are more strongly associated with cardio-metabolic risks than BMI.
To provide ...similar quantitative tools for North American children, we created smoothed centile charts and LMS tables for WHtR and WC based on data from the US National Health and Nutrition Survey, cycle III (NHANES III, N = 11,930 aged 2-24 y 1988-1994).
Applying these reference charts to subsequent NHANES survey cycles, 1999-2012) demonstrated a significant mean increase in both Z-scores of approximately 0.30 SD. In measuring the strength of the association between anthropometric measures and cardio-metabolic risk factors, a unit change in Z-scores for WHtR, WC, and BMI significantly increased the odds of an adverse outcome in all cases (1.18-2.03, P < 0.0001). Z-scores for both measures of central adiposity were significantly more strongly associated with cardio-metabolic comorbidities than BMI-Z.
Since Z-scores permit standardized comparisons across ages and genders, they are useful measures of central adiposity in both clinical or research settings. By providing LMS tables for children and adolescents based on North American reference data, we hope to provide quantitative tools for the study of obesity and its complications.
Abstract
Increasing numbers of youth identify as transgender or gender-diverse (TGD). Many paediatricians and primary care providers (PCPs) will encounter this population in their practice, either ...for gender-related care or general health needs. This statement is intended as a resource to guide paediatricians and PCPs in implementing an affirming approach to routine health care provision for all youth. Furthermore, it presents information to assist providers in responding to requests for counselling from TGD youth and their families around potential options for medical transition, and in making referrals to specialized services, if desired and relevant. Finally, as demand for gender-affirming care is anticipated to continue to increase, some health care providers (HCPs) may wish to develop the knowledge and skills required to initiate adolescents on hormone-blocking agents and gender-affirming hormones. This document is not intended to be a clinical practice guideline, but will provide foundational information regarding these potential components of gender-affirming care, recognizing that the needs and goals of individual adolescents may or may not include such interventions. Additional resources relevant to developing the expertise required to provide gender-affirming interventions will also be identified.
The dermal papilla (DP) provide instructive signals required to activate epithelial progenitors and initiate hair follicle regeneration. DP cell numbers fluctuate over the hair cycle, and hair loss ...is associated with gradual depletion/atrophy of DP cells. How DP cell numbers are maintained in healthy follicles remains unclear. We performed in vivo fate mapping of adult hair follicle dermal sheath (DS) cells to determine their lineage relationship with DP and found that a subset of DS cells are retained following each hair cycle, exhibit self-renewal, and repopulate the DS and the DP with new cells. Ablating these hair follicle dermal stem cells and their progeny retarded hair regrowth and altered hair type specification, suggesting that they function to modulate normal DP function. This work identifies a bipotent stem cell within the adult hair follicle mesenchyme and has important implications toward restoration of hair growth after injury, disease, and aging.
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•Self-renewing hair follicle dermal stem cells (hfDSCs) reside in the dermal sheath•hfDSCs regenerate the dermal sheath and populate the dermal papilla with new cells•The hair follicle niche contains active and quiescent hfDSCs•hfDSCs and their progeny modulate hair growth and specify hair type
Using in vivo fate mapping, Rahmani et al. demonstrate the existence of a bipotent dermal stem cell (hfDSC) that resides in adult hair follicles. At the beginning of each regenerative cycle, hfDSCs repopulate the inductive dermal papilla and dermal sheath and ultimately function to modulate hair growth rate and specify hair type.
Résumé
Un nombre croissant de jeunes s’identifient comme transgenres ou de diverses identités de genre. De nombreux pédiatres et dispensateurs de soins de première ligne accueilleront cette ...population dans leur pratique, dans le cadre de soins liés au genre ou de soins de santé généraux. Le présent document de principes se veut une ressource pour orienter les pédiatres et les dispensateurs de soins de première ligne à adopter une approche d’affirmation pour la prestation des soins réguliers à tous les jeunes. De plus, il contient de l’information visant à aider les dispensateurs à répondre aux demandes de conseils des jeunes transgenres et de diverses identités de genre et de leur famille au sujet des possibilités de transition médicale et d’orientation vers des services spécialisés s’ils le désirent et le jugent pertinent. Enfin, on anticipe que la demande de soins d’affirmation de genre continue d’augmenter, et certains dispensateurs de soins peuvent souhaiter acquérir les connaissances et les habiletés nécessaires pour amorcer les inhibiteurs d’hormones et les hormones d’affirmation de genre chez les adolescents. Le présent document ne contient pas de directives cliniques, mais de l’information fondamentale au sujet des divers éléments possibles des soins d’affirmation de genre, tout en reconnaissant que les besoins et les objectifs d’adolescents particuliers n’incluent pas automatiquement de telles interventions. D’autres ressources permettant d’acquérir les compétences nécessaires pour offrir des interventions d’affirmation de genre sont également proposées.
The immune system plays an important role in regulating tumor growth and metastasis. Classical monocytes promote tumorigenesis and cancer metastasis, but how nonclassical "patrolling" monocytes (PMo) ...interact with tumors is unknown. Here we show that PMo are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack PMo, showed increased lung metastasis in vivo. Transfer of Nr4a1-proficient PMo into Nr4a1-deficient mice prevented tumor invasion in the lung. PMo established early interactions with metastasizing tumor cells, scavenged tumor material from the lung vasculature, and promoted natural killer cell recruitment and activation. Thus, PMo contribute to cancer immunosurveillance and may be targets for cancer immunotherapy.
Protein synthesis is crucial for the maintenance of long-term-memory-related synaptic plasticity. The prion-like cytoplasmic polyadenylation element-binding protein 3 (CPEB3) regulates the ...translation of several mRNAs important for long-term synaptic plasticity in the hippocampus. Here, we provide evidence that the prion-like aggregation and activity of CPEB3 is controlled by SUMOylation. In the basal state, CPEB3 is a repressor and is soluble. Under these circumstances, CPEB3 is SUMOylated in hippocampal neurons both in vitro and in vivo. Following neuronal stimulation, CPEB3 is converted into an active form that promotes the translation of target mRNAs, and this is associated with a decrease of SUMOylation and an increase of aggregation. A chimeric CPEB3 protein fused to SUMO cannot form aggregates and cannot activate the translation of target mRNAs. These findings suggest a model whereby SUMO regulates translation of mRNAs and structural synaptic plasticity by modulating the aggregation of the prion-like protein CPEB3.
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•CPEB3 is SUMOylated in hippocampal neurons•CPEB3 regulates SUMO-2 translation•SUMO-2 inhibits aggregation of CPEB3•Following neuronal activity, CPEB3 SUMOylation is decreased
Drisaldi et al. argue that, under basal, unstimulated conditions, CPEB3 is SUMOylated and mostly soluble. After neuronal stimulation, CPEB3 becomes deSUMOylated and more aggregated. DeSUMOylation and aggregation are two crucial steps required for the translation of the mRNA targets of CPEB3 and for dendritic filopodia formation.
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