Psychosexual development in men with congenital hypogonadotropic hypogonadism on long-term treatment: a mixed methods study.

INTRODUCTION: Congenital hypogonadotropic hypogonadism (CHH) is a rare, genetic, reproductive endocrine disorder characterized by absent puberty and infertility. Limited information is available on the psychosocial impact of CHH and psychosexual development in these patients. AIM: The aim of this study was to determine the impact of CHH on psychosexual development in men on long-term treatment. METHODS: A sequential mixed methods explanatory design was used. First, an online survey (quantitative) was used to quantify the frequency of psychosexual problems among CHH men. Second, patient focus groups (qualitative) were conducted to explore survey findings in detail and develop a working model to guide potential nursing and interdisciplinary interventions. MAIN OUTCOME MEASURES: Patient characteristics, frequency of body shame, difficulty with intimate relationships, and never having been sexually active were assessed. Additionally, we collected subjective patient-reported outcomes regarding the impact of CHH on psychological/emotional well-being, intimate relationships, and sexual activity. RESULTS: A total of 101 CHH men on long-term treatment (>1 year) were included for the analysis of the online survey (mean age 37 ± 11 years, range 19-66, median 36). Half (52/101, 51%) of the men had been seen at a specialized academic center and 37/101 (37%) reported having had fertility-inducing treatment. A high percentage of CHH men experience psychosexual problems including difficulty with intimate relationships (70%) and body image concerns/body shame (94/101, 93%), and the percentage of men never having been sexually active is five times the rate in a reference group (26% vs. 5.4%, P < 0.001). Focus groups revealed persisting body shame and low self-esteem despite long-term treatment that has lasting impact on psychosexual functioning. CONCLUSIONS: CHH men frequently experience psychosexual problems that pose barriers to intimate relationships and initiating sexual activity. These lingering effects cause significant distress and are not ameliorated by long-term treatment. Psychosexual assessment in CHH men with appropriate psychological support and treatment should be warranted in these patients. Dwyer AA, Quinton R, Pitteloud N, and Morin D. Psychosexual development in men with congenital hypogonadotropic hypogonadism on long-term treatment: A mixed methods study. Sex Med 2015;3:32-41

Identifying the unmet health needs of patients with congenital hypogonadotropic hypogonadism using a web-based needs assessment: implications for online interventions and peer-to-peer support.

BACKGROUND: Patients with rare diseases such as congenital hypogonadotropic hypogonadism (CHH) are dispersed, often challenged to find specialized care and face other health disparities. The internet has the potential to reach a wide audience of rare disease patients and can help connect patients and specialists. Therefore, this study aimed to: (i) determine if web-based platforms could be effectively used to conduct an online needs assessment of dispersed CHH patients; (ii) identify the unmet health and informational needs of CHH patients and (iii) assess patient acceptability regarding patient-centered, web-based interventions to bridge shortfalls in care. METHODS: A sequential mixed-methods design was used: first, an online survey was conducted to evaluate health promoting behavior and identify unmet health and informational needs of CHH men. Subsequently, patient focus groups were held to explore specific patient-identified targets for care and to examine the acceptability of possible online interventions. Descriptive statistics and thematic qualitative analyses were used. RESULTS: 105 male participants completed the online survey (mean age 37 ± 11, range 19-66 years) representing a spectrum of patients across a broad socioeconomic range and all but one subject had adequate healthcare literacy. The survey revealed periods of non-adherence to treatment (34/93, 37%) and gaps in healthcare (36/87, 41%) exceeding one year. Patient focus groups identified lasting psychological effects related to feelings of isolation, shame and body-image concerns. Survey respondents were active internet users, nearly all had sought CHH information online (101/105, 96%), and they rated the internet, healthcare providers, and online community as equally important CHH information sources. Focus group participants were overwhelmingly positive regarding online interventions/support with links to reach expert healthcare providers and for peer-to-peer support. CONCLUSION: The web-based needs assessment was an effective way to reach dispersed CHH patients. These individuals often have long gaps in care and struggle with the psychosocial sequelae of CHH. They are highly motivated internet users seeking information and tapping into online communities and are receptive to novel web-based interventions addressing their unmet needs

Squeezed light for advanced gravitational wave detectors and beyond

Recent experiments have demonstrated that squeezed vacuum states can be injected into gravitational wave detectors to improve their sensitivity at detection frequencies where they are quantum noise limited. Squeezed states could be employed in the next generation of more sensitive advanced detectors currently under construction, such as Advanced LIGO, to further push the limits of the observable gravitational wave Universe. To maximize the benefit from squeezing, environmentally induced disturbances such as back scattering and angular jitter need to be mitigated. We discuss the limitations of current squeezed vacuum sources in relation to the requirements imposed by future gravitational wave detectors, and show a design for squeezed light injection which overcomes these limitations

Beyond hormone replacement: quality of life in women with congenital hypogonadotropic hypogonadism.

Little is known about how women with isolated GnRH deficiency cope with their condition. This study aimed to examine the health and informational needs of women with congenital hypogonadotropic hypogonadism (CHH) and evaluate if their experiences differ from women with more common forms of infertility. Cross-sectional, multiple methods study using web-based data collection to reach dispersed rare disease patients. A community-based participatory research framework was employed to develop an online survey and collect quantitative and qualitative data. Adult women diagnosed with CHH who had received at least one year of hormonal treatment completed the Morisky Medication Adherence Scale, Revised Illness Perception Questionnaire and Zung Self-Rating Depression Scale. Information on health care experiences, treatment outcomes and patient-reported challenges were also collected. Women (n = 55) were often diagnosed late (20.7 ± 7.4, range: 10-48 years) and 16/20 patients receiving fertility treatment conceived. Poor adherence was frequently observed (34/55) while more than half (27/49) reported a gap in treatment exceeding a year. Low adherence correlated with depressive symptoms (r = 0.3, P > 0.05). Negative illness perceptions were pervasive and 30/55 exhibited some depressive symptoms - significantly greater than women with common female factor infertility (P < 0.01). Symptoms were underappreciated by providers as only 15 of 55 patients had discussions about psychological services. Women identified isolation, need for information and finding expert care as challenges to living with CHH. Despite being a treatable form of female infertility, the presumable availability of treatment does not necessarily ensure adequate quality of life for women with isolated GnRH deficiency

Real-time Profiling of Solid-State Nanopores During Solution-Phase Nanofabrication

We describe a method for simply characterizing the size and shape of a nanopore during solution-based fabrication and surface modification, using only low-overhead approaches native to conventional nanopore measurements. Solution-based nanopore fabrication methods are democratizing nanopore science by supplanting the traditional use of charged-particle microscopes for fabrication, but nanopore profiling has customarily depended on microscopic examination. Our approach exploits the dependence of nanopore conductance in solution on nanopore size, shape, and surface chemistry in order to characterize nanopores. Measurements of the changing nanopore conductance during formation by etching or deposition can be analyzed using our method to characterize the nascent nanopore size and shape—beyond the typical cylindrical approximation—in real-time. Our approach thus accords with ongoing efforts to broaden the accessibility of 3 nanopore science from fabrication through use: it is compatible with conventional instrumentation and offers straightforward nanoscale characterization of the core tool of the field

The effect of clinical decision making for initiation of systemic anticancer treatments in response to the COVID-19 pandemic in England: a retrospective analysis

BACKGROUND: Cancer services worldwide had to adapt in response to the COVID-19 pandemic to minimise risk to patients and staff. We aimed to assess the national impact of COVID-19 on the prescribing of systemic anticancer treatment in England, immediately after lockdown and after the introduction of new treatments to reduce patient risk. METHODS: We did a retrospective analysis using data from a central National Health Service England web database mandated for clinicians to register intention to start all new systemic anticancer treatments approved for use in England since 2016. We analysed the monthly number of treatment registrations in April, 2020, after the implementation of societal lockdown on March 23, 2020, and after implementation of treatment options to reduce patient risk such as oral or less immunosuppressive drugs, in May and June, 2020. We compared the number of registrations in April-June, 2020, with the mean number of registrations and SD during the previous 6 months of unaffected cancer care (September, 2019, to February, 2020). We calculated the percentage change and absolute difference in SD units for the number of registrations overall, by tumour type, and by type and line of therapy. FINDINGS: In April, 2020, 2969 registrations were recorded, representing 1417 fewer registrations than in the control period (monthly mean 4386; 32% reduction, absolute difference 4·2 SDs, p<0·0001). In May, 2020, total registrations increased to 3950, representing a 10% reduction compared with the control period (absolute difference 1·3 SDs, p<0·0001). In June, 2020, 5022 registrations were recorded, representing a 15% increase compared with the control period (absolute difference 1·9 SDs; p<0·0001]). INTERPRETATION: After the onset of the COVID-19 pandemic, there was a reduction in systemic anticancer treatment initiation in England. However, following introduction of treatment options to reduce patient risk, registrations began to increase in May, 2020, and reached higher numbers than the pre-pandemic mean in June, 2020, when other clinical and societal risk mitigation factors (such as telephone consultations, facemasks and physical distancing) are likely to have contributed. However, outcomes of providing less treatment or delaying treatment initiation, particularly for advanced cancers and neoadjuvant therapies, require continued assessment. FUNDING: None

White Paper: Measuring the Neutrino Mass Hierarchy

This white paper is a condensation of a report by a committee appointed jointly by the Nuclear Science and Physics Divisions at Lawrence Berkeley National Laboratory (LBNL). The goal of this study was to identify the most promising technique(s) for resolving the neutrino mass hierarchy. For the most part, we have relied on calculations and simulations presented by the proponents of the various experiments. We have included evaluations of the opportunities and challenges for these experiments based on what is available already in the literature.Comment: White paper prepared for Snowmass-201

Search for Sterile Neutrinos with a Radioactive Source at Daya Bay

The far site detector complex of the Daya Bay reactor experiment is proposed as a location to search for sterile neutrinos with > eV mass. Antineutrinos from a 500 kCi 144Ce-144Pr beta-decay source (DeltaQ=2.996 MeV) would be detected by four identical 20-ton antineutrino targets. The site layout allows flexible source placement; several specific source locations are discussed. In one year, the 3+1 sterile neutrino hypothesis can be tested at essentially the full suggested range of the parameters Delta m^2_{new} and sin^22theta_{new} (90% C.L.). The backgrounds from six nuclear reactors at >1.6 km distance are shown to be manageable. Advantages of performing the experiment at the Daya Bay far site are described

Auto-calibration of ultrasonic lubricant-film thickness measurements

The measurement of oil film thickness in a lubricated component is essential information for performance monitoring and design. It is well established that such measurements can be made ultrasonically if the lubricant film is modelled as a collection of small springs. The ultrasonic method requires that component faces are separated and a reference reflection recorded in order to obtain a reflection coefficient value from which film thickness is calculated. The novel and practically useful approach put forward in this paper and validated experimentally allows reflection coefficient measurement without the requirement for a reference. This involves simultaneously measuring the amplitude and phase of an ultrasonic pulse reflected from a layer. Provided that the acoustic properties of the substrate are known, the theoretical relationship between the two can be fitted to the data in order to yield reflection coefficient amplitude and phase for an infinitely thick layer. This is equivalent to measuring a reference signal directly, but importantly does not require the materials to be separated. The further valuable aspect of this approach, which is demonstrated experimentally, is its ability to be used as a self-calibrating routine, inherently compensating for temperature effects. This is due to the relationship between the amplitude and phase being unaffected by changes in temperature which cause unwanted changes to the incident pulse. Finally, error analysis is performed showing how the accuracy of the results can be optimized. A finding of particular significance is the strong dependence of the accuracy of the technique on the amplitude of reflection coefficient input data used. This places some limitations on the applicability of the technique. © 2008 IOP Publishing Ltd

Binding of the Bacillus subtilis LexA protein to the SOS operator

The Bacillus subtilis LexA protein represses the SOS response to DNA damage by binding as a dimer to the consensus operator sequence 5′-CGAACN(4)GTTCG-3′. To characterize the requirements for LexA binding to SOS operators, we determined the operator bases needed for site-specific binding as well as the LexA amino acids required for operator recognition. Using mobility shift assays to determine equilibrium constants for B.subtilis LexA binding to recA operator mutants, we found that several single base substitutions within the 14 bp recA operator sequence destabilized binding enough to abolish site-specific binding. Our results show that the AT base pairs at the third and fourth positions from the 5′ end of a 7 bp half-site are essential and that the preferred binding site for a LexA dimer is 5′-CGAACATATGTTCG-3′. Binding studies with LexA mutants, in which the solvent accessible amino acid residues in the putative DNA binding domain were mutated, indicate that Arg-49 and His-46 are essential for binding and that Lys-53 and Ala-48 are also involved in operator recognition. Guided by our mutational analyses as well as hydroxyl radical footprinting studies of the dinC and recA operators we docked a computer model of B.subtilis LexA on the preferred operator sequence in silico. Our model suggests that binding by a LexA dimer involves bending of the DNA helix within the internal 4 bp of the operator