In adolescents, testosterone may have several effects including promotion of secondary sexual characteristics and pubertal growth, attainment of optimal muscle mass and peak bone mass, optimization ...of the metabolic profile, and psychosocial maturation and well-being.
Testosterone therapy is a cornerstone of the management of hypogonadism in boys. Since the initial report of the chemical synthesis of testosterone, several formulations have continued to develop, and although many of these have been used in boys, none of them have been studied in detail in this age group. Given the wide ranging effects of testosterone, the level of evidence for their effects in boys and the heterogeneity of conditions that lead to early-onset hypogonadism, a standardized protocol for monitoring testosterone replacement in this age group is needed. Key Messages: In this review, we focus on the perceived benefits of androgen replacement in boys affected by pubertal delay and highlight the need to improve the health monitoring of boys who receive androgen replacement therapy, proposing different approaches based on the underlying pathophysiology.
The strong Coulombic interactions in miniaturized structures can lead to efficient carrier multiplication, which is essential for many-body physics and design of efficient photonic devices beyond ...thermodynamic conversion limits. However, carrier multiplication has rarely been realized in layered semiconducting materials despite strong electronic interactions. Here, we report the experimental observation of unusual carrier multiplication in a multilayer black phosphorus device. Electric field-dependent Hall measurements confirm a substantial increase of carrier density in multilayer black phosphorus channel, which is attributed to the impact ionization by energetic carriers. This mechanism relies on the generation of self-heating induced charge carriers under the large electric field due to competition between electron-electron and electron-phonon interactions in the direct and narrow band gap (0.3 eV) of the multilayer black phosphorus. These findings point the way toward utilization of carrier multiplication to enhance the performance of electronics and optoelectronics devices based on two-dimensional materials.
To explore the current models of practice in centres delivering specialist care for children with disorders of sex development (DSD), an international survey of 124 clinicians, identified through ...DSDnet and the I-DSD Registry, was performed in the last quarter of 2014.
A total of 78 (63 %) clinicians, in 75 centres, from 38 countries responded to the survey. A formal national network for managing DSD was reported to exist in 12 (32 %) countries. The paediatric specialists routinely involved in the initial evaluation of a newborn included: endocrinologist (99 %), surgeon/urologist (95 %), radiologist (93 %), neonatologist (91 %), clinical geneticist (81 %) and clinical psychologist (69 %). A team consisting of paediatric specialists in endocrinology, surgery/urology, clinical psychology, and nursing was only possible in 31 (41 %) centres. Of the 75 centres, 26 (35 %) kept only a local DSD registry and 40 (53 %) shared their data in a multicentre DSD registry. Attendance in local, national and international DSD-related educational programs was reported by 69, 78 and 84 % clinicians, respectively. Participation in audits/quality improvement exercises in DSD care was reported by 14 (19 %) centres. In addition to complex biochemistry and molecular genetic investigations, 40 clinicians (51 %) also had access to next generation sequencing. A genetic test was reported to be more preferable than biochemical tests for diagnosing 5-alpha reductase deficiency and 17-beta hydroxysteroid dehydrogenase 3 deficiency by 50 and 55 % clinicians, respectively.
DSD centres report a high level of interaction at an international level, have access to specialist staff and are increasingly relying on molecular genetics for routine diagnostics. The quality of care provided by these centres locally requires further exploration.
Summary Background Children with osteogenesis imperfecta are often treated with intravenous bisphosphonates. We aimed to assess the safety and efficacy of risedronate, an orally administered ...third-generation bisphosphonate, in children with the disease. Methods In this multicentre, randomised, parallel, double-blind, placebo-controlled trial, children aged 4–15 years with osteogenesis imperfecta and increased fracture risk were randomly assigned by telephone randomisation system in a 2:1 ratio to receive either daily risedronate (2·5 or 5 mg) or placebo for 1 year. Study treatment was masked from patients, investigators, and study centre personnel. Thereafter, all children received risedronate for 2 additional years in an open-label extension. The primary efficacy endpoint was percentage change in lumbar spine areal bone mineral density (BMD) at 1 year. The primary efficacy analysis was done by ANCOVA, with treatment, age group, and pooled centre as fixed effects, and baseline as covariate. Analyses were based on the intention-to-treat population, which included all patients who were randomly assigned and took at least one dose of assigned study treatment. The trial is registered with ClinicalTrials.gov , number NCT00106028. Findings Of 147 patients, 97 were randomly assigned to the risedronate group and 50 to the placebo group. Three patients from the risedronate group and one from the placebo group did not receive study treatment, leaving 94 and 49 in the intention-to-treat population, respectively. The mean increase in lumbar spine areal BMD after 1 year was 16·3% in the risedronate group and 7·6% in the placebo group (difference 8·7%, 95% CI 5·7–11·7; p<0·0001). After 1 year, clinical fractures had occurred in 29 (31%) of 94 patients in the risedronate group and 24 (49%) of 49 patients in the placebo group (p=0·0446). During years 2 and 3 (open-label phase), clinical fractures were reported in 46 (53%) of 87 patients in the group that had received risedronate since the start of the study, and 32 (65%) of 49 patients in the group that had been given placebo during the first year. Adverse event profiles were otherwise similar between the two groups, including frequencies of reported upper-gastrointestinal and selected musculoskeletal adverse events. Interpretation Oral risedronate increased areal BMD and reduced the risk of first and recurrent clinical fractures in children with osteogenesis imperfecta, and the drug was generally well tolerated. Risedronate should be regarded as a treatment option for children with osteogenesis imperfecta. Funding Alliance for Better Bone Health (Warner Chilcott and Sanofi).
The purpose of the study is to investigate the impact of organizational justice, in Punjab Police, with reference to its subtypes on job satisfaction in the aftermath of the Model Town incident which ...severely damage their organizational fabric. This is a study adopting a quantitative research design, data collected from Punjab Police by the SRS sampling approach. The conventional relationship between justice and satisfaction is proved with significant deviations in granular dependencies. For Police, the procedural justice is insignificantly correlated with distributive and interactional justices which results in statistical insignificant dependence of job satisfaction on these two components of the organizational justice. The study is limited only to the Punjab Police as they are affected the most from the Model Town incident. The study is based upon the organizational justice theory and focuses on the impact of a high valued incident on the organizational fabric of the Police in special, and the security agencies in general.
Adrenal insufficiency (AI) is a life-threatening condition requiring life-long glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises. The number of ...individuals with primary and secondary adrenal insufficiency in Europe is estimated to be 20–50/100.000. A growing number of AI cases are due to side effects of GC treatment used in different treatment strategies for cancer and to immunotherapy in cancer treatment. The benefit of hormone replacement therapy is evident but long-term adverse effects may arise due to the non-physiological GC doses and treatment regimens used. Given multiple GC replacement formulations available comprising short-acting, intermediate, long-acting and novel modified-release hydrocortisone as well as subcutaneous formulations, this review offers a concise summary on the latest therapeutic improvements for treatment of AI and prevention of adrenal crises. As availability of various glucocorticoid formulations and access to expert centers across Europe varies widely, European Reference Networks on rare endocrine conditions aim at harmonizing treatment and ensure access to specialized patient care for individual case-by-case treatment decisions. To improve the availability across Europe to cost effective oral and parenteral formulations of hydrocortisone will save lives.
Missing spatial data is one of the major concerns associated with the application of satellite data. The Data INterpolating Empirical Orthogonal Functions (DINEOF) method has been proven to be an ...effective tool for filling spatial gaps in various satellite data products. The Ariake Sea, which is a turbid coastal sea, shows the large spatial and temporal variability of chlorophyll-a (Chl-a) and total suspended matter (TSM). However, ocean color satellite data for this region usually have large gaps, which affects the accurate analysis of Chl-a and TSM variability. In this study, we applied the DINEOF method to fill the missing pixels from the regionally tuned Moderate Resolution Imaging Spectroradiometer (MODIS)-Aqua (hereafter, MODIS) Chl-a and MODIS-derived TSM datasets for the period 2002–2017. The validation results showed that the DINEOF reconstructed data were accurate and reliable. Furthermore, the Empirical Orthogonal Functions (EOF) analysis based on the reconstructed data was used to quantitatively analyze the spatial and temporal variability of Chl-a and TSM at both monthly and individual events of spring-neap tidal scales. The first three EOF modes of Chl-a showed seasonal variability mainly caused by precipitation, the sea surface temperature (SST), and river discharge for the first EOF mode and the sea level amplitude for the second. The first three EOF modes of TSM exhibited both seasonal and spring-neap tidal variability. The first and second EOF modes of TSM displayed spring-neap tidal variability caused by the sea level amplitude. The second EOF mode of TSM also showed seasonal variability caused by the sea level amplitude. In this study, we first applied the DINEOF method to reconstruct the satellite data and to capture the major spatial and temporal variability of Chl-a and TSM for the Ariake Sea. Our results demonstrate that the DINEOF method can reconstruct patchy oceanic color datasets and improve spatio-temporal variability analysis.
Provision of optimum healthcare for infants with atypical genitalia requires a clear understanding of the occurrence of this condition. The objective of this study was to determine the prevalence of ...atypical genitalia and its initial management. A prospective, electronic survey of clinicians within managed clinical networks in Scotland was undertaken between 2013 and 2019. Notification from clinicians was sought for term neonates requiring specialist input for atypical genitalia. Additional information was also sought from the 4 regional genetics laboratories that provided details for neonates who had an urgent karyotype performed for atypical genitalia or sex determination. In total, the study identified 171 term infants who required some investigation for atypical genitalia in the neonatal period, providing a birth prevalence of 1:1,881 term births. Of the 171 infants, 97 (57%) had specialist input over the first 3 months of life, providing a birth prevalence of 1:3,318 term births that received specialist input for atypical genitalia. A total of 92 of these 97 cases had complete 3-month follow-up data, 62 (67%) presented within 24 h of birth, and age at presentation ranged from birth to 28 days. Age at sex assignment ranged from birth to 14 days, and in 63 cases (68%), sex assignment occurred at birth. Thus, the birth prevalence of a case of atypical genitalia where sex assignment was reported to be delayed beyond birth was estimated at 1:11,097 births. In 1 case sex was re-assigned at 3 months. Atypical genitalia requiring specialist input within the first month of life are rare in term newborns, and in only a third of these cases, sex assignment is delayed beyond birth. This study provides new clinical benchmarks for comparing and improving the delivery of care in centres that manage these conditions.
The association between chronic obstructive pulmonary disease (COPD) and occupational exposures are less studied in Bangladeshi context, despite the fact that occupational exposures are serious ...public health concerns in Bangladesh. Therefore, this study aimed to evaluate this association considering demographic, health and smoking characteristics of Bangladeshi population. This was a hospital-based quantitative study including 373 participants who were assessed for COPD through spirometry testing. Assessment of occupational exposures was based on both self-reporting by respondents and ALOHA based job exposure matrix (JEM). Here, among the self-reported exposed group (n = 189), 104 participants (55%) were found with COPD compared to 23 participants (12.5%) in unexposed group (n = 184) that differed significantly (p = 0.00). Similarly, among the JEM measured low (n = 103) and high exposed group (n = 236), 23.3% and 41.5% of the participants were found with COPD respectively; compared to unexposed group (14.7%; n = 34), that differed significantly also (p = 0.00). Likewise, participants with longer self-reported occupational exposures (>8 years) showed significantly (p = 0.00) higher proportions of COPD (79.5%) compared to 40.4% in shorter exposure group (1-8 years). Similarly, significant (p = 0.00) higher cases of COPD were observed among the longer cumulative exposure years (>9 years) group than the shorter cumulative exposure years (1-9 years) group in JEM. While combining smoking and occupational exposure, the chance of developing COPD among the current, former and non-smokers of exposed group were 7.4, 7.2 and 12.7 times higher respectively than unexposed group. Furthermore, logistic analysis revealed that after adjustments for confounding risk factors, the chance of developing COPD among the self-reported exposure group was 6.3 times higher (ORs: 6.3, p = 0.00) than unexposed group; and JEM exposure group has odds of 2.8 and 1.1 respectively (p0.05) for high and low exposures. Further studies are needed to reinforce this association between COPD and occupational exposure in Bangladesh.
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