Author Correction: Global glacier mass changes and their contributions to sea-level rise from 1961 to 2016.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Global glacier mass changes and their contributions to sea-level rise from 1961 to 2016.

Glaciers distinct from the Greenland and Antarctic ice sheets cover an area of approximately 706,000 square kilometres globally1, with an estimated total volume of 170,000 cubic kilometres, or 0.4 metres of potential sea-level-rise equivalent2. Retreating and thinning glaciers are icons of climate change3 and affect regional runoff4 as well as global sea level5,6. In past reports from the Intergovernmental Panel on Climate Change, estimates of changes in glacier mass were based on the multiplication of averaged or interpolated results from available observations of a few hundred glaciers by defined regional glacier areas7-10. For data-scarce regions, these results had to be complemented with estimates based on satellite altimetry and gravimetry11. These past approaches were challenged by the small number and heterogeneous spatiotemporal distribution of in situ measurement series and their often unknown ability to represent their respective mountain ranges, as well as by the spatial limitations of satellite altimetry (for which only point data are available) and gravimetry (with its coarse resolution). Here we use an extrapolation of glaciological and geodetic observations to show that glaciers contributed 27 ± 22 millimetres to global mean sea-level rise from 1961 to 2016. Regional specific-mass-change rates for 2006-2016 range from -0.1 metres to -1.2 metres of water equivalent per year, resulting in a global sea-level contribution of 335 ± 144 gigatonnes, or 0.92 ± 0.39 millimetres, per year. Although statistical uncertainty ranges overlap, our conclusions suggest that glacier mass loss may be larger than previously reported11. The present glacier mass loss is equivalent to the sea-level contribution of the Greenland Ice Sheet12, clearly exceeds the loss from the Antarctic Ice Sheet13, and accounts for 25 to 30 per cent of the total observed sea-level rise14. Present mass-loss rates indicate that glaciers could almost disappear in some mountain ranges in this century, while heavily glacierized regions will continue to contribute to sea-level rise beyond 2100.

Successes and challenges of partnership working to tackle health inequalities using collaborative approaches to community-based research: mixed methods analysis of focus group evidence.

BACKGROUND: The concept of collaborative approaches involves community residents in joint decision-making processes to maintain or enhance their material and social conditions. During COVID-19, public services saw the benefits of actively collaborating with communities and involving residents in decision-making processes. As communities have resources and assets, they are well-placed to contribute to developing local health and wellbeing initiatives. An interdisciplinary and nationally funded three-phase research programme, "Mobilising community assets to tackle health inequalities", was established with the objective of utilising local, cultural, and natural assets to support health and wellbeing. The current study aimed to synthesise evidence collected by research teams awarded funding in phase one of the programme, comprising academic and non-academic, health and social care, voluntary and community partners. METHODS: Ten online focus groups were conducted with research teams from across the UK exploring the successes and challenges of partnership working to tackle health inequalities using collaborative approaches to community-based research. Eight focus group questions were split between partnership working and health inequalities. RESULTS: Thematic and content analysis produced 185 subthemes from which 12 themes were identified. Major themes representing an above average number of coded responses were research evidence; funding; relationships with partners; health inequalities and deprivation; community involvement; and health service and integrated care systems. Minor themes were link workers and social prescribing; training and support; place-based factors; longevity of programmes; setting up and scaling up programmes; and mental health. CONCLUSIONS: Successes included employing practice-based and arts-based methods, being part of a research project for those not normally involved in research, sharing funding democratically, building on established relationships, and the vital role that local assets play in involving communities. Challenges involved a lack of sustainable financial support, the short-term nature of funding, inconsistencies in reaching the poorest people, obtaining the right sort of research evidence, making sufficient research progress, building relationships with already over-burdened health care staff, and redressing the balance of power in favour of communities. Despite the challenges, participants were mainly optimistic that collective approaches and meaningful co-production would create opportunities for future research partnerships with communities.

Line manager training and organizational approaches to supporting well-being.

BACKGROUND: Employee mental health and well-being (MH&WB) is critical to the productivity and success of organizations. Training line managers (LMs) in mental health plays an important role in protecting and enhancing employee well-being, but its relationship with other MH&WB practices is under-researched. AIMS: To determine whether organizations offering LM training in mental health differ in the adoption of workplace- (i.e. primary/prevention-focused) and worker-directed (including both secondary/resiliency-focused and tertiary/remedial-focused) interventions to those organizations not offering LM training and to explore changes in the proportions of activities offered over time. METHODS: Secondary analysis of enterprise data from computer-assisted telephone interview surveys. The analysis included data from organizations in England across 4 years (2020: n = 1900; 2021: n = 1551; 2022: n = 1904; 2023: n = 1902). RESULTS: Offering LM training in mental health was associated with organizations' uptake of primary-, secondary-, and tertiary-level MH&WB activities across all 4 years. The proportion of organizations offering primary-, secondary- and tertiary-level interventions increased over time. On average, tertiary-level activities were most adopted (2020: 80%; 2021: 81%; 2022: 84%; 2023: 84%), followed by primary-level activities (2020: 66%; 2021: 72%; 2022: 72%; 2023: 73%) and secondary-level activities (2020: 62%; 2021: 60%; 2022: 61%; 2023: 67%). CONCLUSIONS: Offering LM training in mental health is associated with the adoption of other MH&WB practices by organizations. Suggesting that organizations that are committed to the mental health agenda are more likely to take a holistic approach (including both worker and workplace strategies) to promoting workforce mental health, rather than providing LM training in isolation.

Typology of employers offering line manager training for mental health.

BACKGROUND: Mental ill health has a high economic impact on society and employers. National and international policy advocates line manager (LM) training in mental health as a key intervention, but little is known about employer training provisions. AIMS: To explore the prevalence and characteristics of organizations that offer LM training in mental health. METHODS: Secondary analysis of existing longitudinal anonymised organizational-level survey data derived from computer-assisted telephone interview surveys collected in four waves (2020:1900 firms, 2021:1551, 2022:1904, 2023:1902) in England, before, during and after a global pandemic. RESULTS: The proportion of organizations offering LM training in mental health increased pre- to post-pandemic (2020:50%, 2023:59%) but 41% do not currently provide it. Logistic regression confirmed that LM training is more likely to be offered by large-sized enterprises, organizations with a larger proportion of employees who are younger (aged 25-49), female, disabled and from ethnic minority communities. Sector patterns were inconsistent, but in 2023, organizations from the 'Hospitality' and 'Business Services' sectors were more likely to provide LM training than other sectors. CONCLUSIONS: Continued efforts are needed to increase the proportion of employers offering LM training in mental health, particularly small- to medium-sized enterprises, and organizations with predominantly male, White and/or older workforces.

The role of cultural, community and natural assets in addressing societal and structural health inequalities in the UK: future research priorities.

BACKGROUND: Reducing health inequalities in the UK has been a policy priority for over 20 years, yet, despite efforts to create a more equal society, progress has been limited. Furthermore, some inequalities have widened and become more apparent, particularly during the Covid-19 pandemic. With growing recognition of the uneven distribution of life expectancy and of mental and physical health, the current research was commissioned to identify future research priorities to address UK societal and structural health inequalities. METHODS: An expert opinion consultancy process comprising an anonymous online survey and a consultation workshop were conducted to investigate priority areas for future research into UK inequalities. The seven-question survey asked respondents (n = 170) to indicate their current role, identify and prioritise areas of inequality, approaches and evaluation methods, and comment on future research priorities. The workshop was held to determine areas of research priority and attended by a closed list of delegates (n = 30) representing a range of academic disciplines and end-users of research from policy and practice. Delegates self-selected one of four breakout groups to determine research priority areas in four categories of inequality (health, social, economic, and other) and to allocate hypothetical sums of funding (half, one, five, and ten million pounds) to chosen priorities. Responses were analysed using mixed methods. RESULTS: Survey respondents were mainly 'academics' (33%), 'voluntary/third sector professionals' (17%), and 'creative/cultural professionals'(16%). Survey questions identified the main areas of inequality as 'health' (58%), 'social care' (54%), and 'living standards' (47%). The first research priority was 'access to creative and cultural opportunities' (37%), second, 'sense of place' (23%), and third, 'community' (17%). Approaches seen to benefit from more research in relation to addressing inequalities were 'health/social care' (55%), 'advice services' (34%), and 'adult education/training' (26%). Preferred evaluation methods were 'community/participatory' (76%), 'action research' (62%), and 'questionnaires/focus groups' (53%). Survey respondents (25%) commented on interactions between inequalities and issues such as political and economic decisions, and climate. The key workshop finding from determining research priorities in areas of inequality was that health equity could only be achieved by tackling societal and structural inequalities, environmental conditions and housing, and having an active prevention programme. CONCLUSIONS: Research demonstrates a clear need to assess the impact of cultural and natural assets in reducing inequality. Collaborations between community groups, service providers, local authorities, health commissioners, GPs, and researchers using longitudinal methods are needed within a multi-disciplinary approach to address societal and structural health inequalities.

Managing employees with dementia: a systematic review.

BACKGROUND: The experience of developing dementia while in employment has been explored from the point of view of the employee, but less is known about the perspectives, experiences and needs of employers. AIMS: To review systematically literature about the management of employees who develop dementia whilst in employment. METHODS: Databases searched included MEDLINE, EMBASE, PsycINFO, CINAHL, BNI, ABI Inform, ISI Web of Science, Open Grey and dementia journals database; 44 documents were identified for inclusion in the review: 22 journal papers, one PhD thesis and 21 articles, reports and webpages from the grey literature. As all documents were qualitative in nature a thematic synthesis of their content was undertaken. RESULTS: Three main themes and ten sub-themes were identified. The main themes concerned early presentation and identification in the workplace; reasonable adjustments for people with working age dementia; and the provision of information to raise awareness and facilitate informed choice. The evidence suggested that there is a lack of awareness about working age dementia and that this may impact negatively on employees. Guidance for employers offered suggestions for good practice. CONCLUSIONS: Guidance for employers is increasingly available although it rarely refers to the evidence base. There is a need for future studies that explore the effectiveness of guidance and training initiatives for employers. Examples of good practice where employees with dementia have been well supported in the workplace and who have been able to leave the workforce with dignity, would be helpful.

Homogeneity and heterogeneity as situational properties: producing--and moving beyond?--race in post-genomic science.

In this article, we explore current thinking and practices around the logics of difference in gene-environment interaction research in the post-genomic era. We find that scientists conducting gene-environment interaction research continue to invoke well-worn notions of racial difference and diversity, but use them strategically to try to examine other kinds of etiologically significant differences among populations. Scientists do this by seeing populations not as inherently homogeneous or heterogeneous, but rather by actively working to produce homogeneity along some dimensions and heterogeneity along others in their study populations. Thus we argue that homogeneity and heterogeneity are situational properties--properties that scientists seek to achieve in their study populations, the available data, and other aspects of the research situation they are confronting, and then leverage to advance post-genomic science. Pointing to the situatedness of homogeneity and heterogeneity in gene-environment interaction research underscores the work that these properties do and the contingencies that shape decisions about research procedures. Through a focus on the situational production of homogeneity and heterogeneity more broadly, we find that gene-environment interaction research attempts to shift the logic of difference from solely racial terms as explanatory ends unto themselves, to racial and other dimensions of difference that may be important clues to the causes of complex diseases.

Arterial stiffness assessment in coronary microvascular dysfunction and heart failure with preserved ejection fraction: An initial report from the WISE-CVD continuation study.

Background: Heart failure with preserved ejection fraction (HFpEF) is the most common cardiac complication in patients with coronary microvascular dysfunction (CMD), yet its underlying pathways remain unclear. Aortic pulse-wave velocity (aPWV) is an indicator of large artery stiffness and a predictor for cardiovascular disease. However, aPWV in CMD and HFpEF is not well characterized and may provide understanding of disease progression. Methods: Among participants without obstructive coronary artery disease, we evaluated 51 women with suspected CMD and 20 women and men with evidence of HFpEF. All participants underwent aPWV measurement (SphygmoCor, Atcor Medical) with higher aPWV indicating greater vascular stiffness. Cardiac magnetic resonance imaging (CMRI) assessed left ventricular (LV) ejection fraction, CMD via myocardial perfusion reserve index (MPRI), and ventricular remodeling via LV mass-volume ratio. . Statistical analysis was performed using Wilcoxon rank sum tests, Pearson correlations and linear regression analysis. Results: Compared to the suspected CMD group, the HFpEF participants were older (65 ± 12 vs 56 ± 11 yrs., p = 0.002) had higher BMI (31.0 ± 4.3 vs 27.8 ± 6.7 kg/m2, p = 0.013), higher aPWV (10.5 ± 2.0 vs 8.0 ± 1.6 m/s, p = 0.05) and lower MPRI (1.5 ± 0.3 vs1.8 ± 0.3, p = 0.02), but not remodeling. In a model adjusted for cardiovascular risk factors, the HFpEF group had a lower LVEF (estimate -4.78, p = 0.0437) than the suspected CMD group. Conclusions: HFpEF participants exhibit greater arterial stiffness and lower myocardial perfusion reserve, with lower LVEF albeit not remodeling, compared to suspected CMD participants. These findings suggest arterial stiffness may contribute to progression from CMD to HFpEF. Prospective work is needed and ongoing.

How do GPs complete fit note comments?

BACKGROUND: The 'fit note' was introduced in the UK in April 2010, to facilitate return to work (RTW). However, no research to date has reported on how general practitioners (GPs) complete the comments section of the fit note. AIMS: To investigate the content of GPs' comments in a sample of actual fit notes. METHODS: Data were collected in a service evaluation of fit notes issued by a regular general practice and those issued by a fit for work service (FFWS), where the fit notes for patients using the service are signed by GPs who have completed or are studying for a Diploma in Occupational Medicine. Content analysis was conducted on the fit note comments. RESULTS: There were 1212 fit notes available for analysis. Seven hundred and twelve were issued by the general practice and 500 by the FFWS. The FFWS made comments in 98% of those who may be fit and 90% of those not fit against 72% and 12%, respectively, for comments by the general practice. Fourteen different categories were identified in the comments. Most comments made some reference to RTW but few described the functional effects of the patient's condition. Comments frequently covered more than one category and appeared to be serving a number of different purposes. CONCLUSIONS: There was a wide variety in how the comments section was completed, and GPs were not completing the fit note as intended. The information provided may require improvement if it is to be useful to employers.

Exploring the potential of creative museum-led activities to support stroke In-patient rehabilitation and wellbeing: A pilot mixed-methods study.

BACKGROUND: This paper proposes a framework for studying the potential of museum-led interventions for supporting stroke rehabilitation goals. METHODS: The intervention was based on Kirvevold et al.'s model for interventions for post-stroke wellbeing. Mixed-methods data wqas collected to review benefits in a pilot study, including retrospective video observations for six sessions with four patients; interviews with patients, carers and facilitators; pre-post patient assessments; and facilitator diaries. RESULTS: Systematic analysis of videos showed high levels of concentration and engagement with museum objects, low levels of social interaction, and positive or neutral mood throughout. Thematic qualitative analysis suggested patients felt engaged in meaningful activities, which lifted negative mood, provided positive distraction from the ward, and increased self-esteem, including belief in patient abilities. CONCLUSION: Further research is needed to fully establish the potential of museum-led interventions for stroke rehabilitation.

Benign soft tissue tumours of the foot & ankle: A pictorial review.

The purpose of this pictorial review is to aid the clinician in distinguishing different benign lesions within the foot and ankle. We discuss the typical clinical and radiological findings as well as management options for intra and extra-compartmental lesions. Differentiation between sarcoma and benign lesions is imperative when presented with any mass in the foot or ankle.

BK viremia surveillance after kidney transplant: single-center experience during a change from cyclosporine-to lower-dose tacrolimus-based primary immunosuppression regimen.

BACKGROUND: The aim was to report our experience of BK viremia surveillance after kidney transplant during a period of change from cyclosporine (CyA)-to lower-dose tacrolimus (Tac)-based primary immunosuppression regimens. METHODS: In a prospective single-center observational cohort study, 68 consecutive patients received renal transplant during the period when we used a CyA-based primary immunosuppression regimen and 66 after we changed to a lower-dose Tac-based regimen. Testing for BK viremia by quantitative polymerase chain reaction assay was performed at least monthly for a minimum of 1 year. RESULTS: Thirty-nine (29.1%) patients developed BK viremia and 2 (1.5%) developed BK nephropathy. The actuarial time to BK viremia was shorter in patients receiving CyA/mycophenolate mofetil (MMF)/prednisolone (Pred) compared with Tac/MMF/Pred (P=0.04) and primary immunosuppression with CyA/MMF/Pred was the only independent predictor of BK viremia (hazard ratio 1.95; P=0.047). Comparing patients who experienced BK viremia and those who did not, there was no difference in incidence of acute rejection (20.5% vs. 25.3%; P=0.56) or estimated glomerular filtration rate at 12 months (48.8 vs. 49.9 mL/min/1.73 m(2)), but the incidence of ureteric stenosis was higher (10.3% vs. 1.1%; P=0.01). CONCLUSIONS: Our data demonstrate a lower incidence of BK viremia in patients on lower-dose Tac compared with CyA-based primary immunosuppression in contrast to previous studies, and provide further support for the association between BK virus and ureteric complications.

Bicarbonate enhances expression of the endocarditis and biofilm associated pilus locus, ebpR-ebpABC, in Enterococcus faecalis.

BACKGROUND: We previously identified ebpR, encoding a potential member of the AtxA/Mga transcriptional regulator family, and showed that it is important for transcriptional activation of the Enterococcus faecalis endocarditis and biofilm associated pilus operon, ebpABC. Although ebpR is not absolutely essential for ebpABC expression (100-fold reduction), its deletion led to phenotypes similar to those of an ebpABC mutant such as absence of pili at the cell surface and, consequently, reduced biofilm formation. A non-piliated ebpABC mutant has been shown to be attenuated in a rat model of endocarditis and in a murine urinary tract infection model, indicating an important participation of the ebpR-ebpABC locus in virulence. However, there is no report relating to the environmental conditions that affect expression of the ebpR-ebpABC locus. RESULTS: In this study, we examined the effect of CO2/HCO3(-), pH, and the Fsr system on the ebpR-ebpABC locus expression. The presence of 5% CO2/0.1 M HCO3(-) increased ebpR-ebpABC expression, while the Fsr system was confirmed to be a weak repressor of this locus. The mechanism by which the Fsr system repressed the ebpR-ebpABC locus expression appears independent of the effects of CO2(-) bicarbonate. Furthermore, by using an ebpA::lacZ fusion as a reporter, we showed that addition of 0.1 M sodium bicarbonate to TSBG (buffered at pH 7.5), but not the presence of 5% CO2, induced ebpA expression in TSBG broth. In addition, using microarray analysis, we found 73 genes affected by the presence of sodium bicarbonate (abs(fold) > 2, P < 0.05), the majority of which belong to the PTS system and ABC transporter families. Finally, pilus production correlated with ebpA mRNA levels under the conditions tested. CONCLUSIONS: This study reports that the ebp locus expression is enhanced by the presence of bicarbonate with a consequential increase in the number of cells producing pili. Although the molecular basis of the bicarbonate effect remains unclear, the pathway is independent of the Fsr system. In conclusion, E. faecalis joins the growing family of pathogens that regulates virulence gene expression in response to bicarbonate and/or CO2.

Art, nature and mental health: assessing the biopsychosocial effects of a 'creative green prescription' museum programme involving horticulture, artmaking and collections.

AIMS: To assess the biopsychosocial effects of participation in a unique, combined arts- and nature-based museum intervention, involving engagement with horticulture, artmaking and museum collections, on adult mental health service users. METHODS: Adult mental health service users (total n = 46 across two phases) with an average age of 53 were referred through social prescribing by community partners (mental health nurse and via a day centre for disadvantaged and vulnerable adults) to a 10-week 'creative green prescription' programme held in Whitworth Park and the Whitworth Art Gallery. The study used an exploratory sequential mixed methods design comprising two phases - Phase 1 (September to December 2016): qualitative research investigating the views of participants (n = 26) through semi-structured interviews and diaries and Phase 2 (February to April 2018): quantitative research informed by Phase 1 analysing psychological wellbeing data from participants (n = 20) who completed the UCL Museum Wellbeing Measure pre-post programme. RESULTS: Inductive thematic analysis of Phase 1 interview data revealed increased feelings of wellbeing brought about by improved self-esteem, decreased social isolation and the formation of communities of practice. Statistical analysis of pre-post quantitative measures in Phase 2 found a highly significant increase in psychological wellbeing. CONCLUSION: Creative green prescription programmes, using a combination of arts- and nature-based activities, present distinct synergistic benefits that have the potential to make a significant impact on the psychosocial wellbeing of adult mental health service users. Museums with parks and gardens should consider integrating programmes of outdoor and indoor collections-inspired creative activities permitting combined engagement with nature, art and wellbeing.

Cryopreservation-induced human sperm DNA damage is predominantly mediated by oxidative stress rather than apoptosis.

BACKGROUND: Whereas studies have revealed that the cryopreservation of human semen increases sperm DNA fragmentation, the mechanisms involved in this type of cryo-injury are largely unknown. Elucidation of these mechanisms may provide insight into preventing such injury. METHODS: We obtained 60 semen samples from 60 men and conducted experiments to determine the cause of cryopreservation-induced DNA fragmentation using 8-oxo-7,8-dihydro-2'deoxyguanosine (8OHdG) as a biomarker of oxidative stress, percentage caspase positive cells as an indicator of apoptosis, the potential antioxidant genistein and the caspase inhibitor Z-VAD(OMe)-FMK. RESULTS: Cryopreservation led to a significant increase in percentage DNA fragmentation, percentage 8OHdG and percentage caspase positive cells (P < 0.001). Percentage DNA fragmentation was positively correlated with percentage 8OHdG before (r = 0.756, P < 0.001) and after cryopreservation (r = 0.528, P = 0.017). The addition of 50 and 100 microM genistein to the cryoprotectant had a significant protective effect on sperm DNA (P < 0.001) although the caspase inhibitor demonstrated no difference to the control. CONCLUSIONS: Human sperm DNA fragmentation is associated with an increase in oxidative stress during cryopreservation, rather than the activation of caspases and apoptosis. The estrogenic compound genistein may be useful in reducing this effect but larger trials are needed to confirm this.

Economic evaluation of a randomized clinical trial of hospital versus telephone follow-up after treatment for breast cancer.

BACKGROUND: This was an economic evaluation of hospital versus telephone follow-up by specialist nurses after treatment for breast cancer. METHODS: A cost minimization analysis was carried out from a National Health Service (NHS) perspective using data from a trial in which 374 women were randomized to telephone or hospital follow-up. Primary analysis compared NHS resource use for routine follow-up over a mean of 24 months. Secondary analyses included patient and carer travel and productivity costs, and NHS and personal social services costs of care in patients with recurrent breast cancer. RESULTS: Patients who had telephone follow-up had approximately 20 per cent more consultations (634 versus 524). The longer duration of telephone consultations and the frequent use of junior medical staff in hospital clinics resulted in higher routine costs for telephone follow-up (mean difference pound 55 (bias-corrected 95 per cent confidence interval (b.c.i.) pound 29 to pound 77)). There were no significant differences in the costs of treating recurrence, but patients who had hospital-based follow-up had significantly higher travel and productivity costs (mean difference pound 47 (95 per cent b.c.i. pound 40 to pound 55)). CONCLUSION: Telephone follow-up for breast cancer may reduce the burden on busy hospital clinics but will not necessarily lead to cost or salary savings.

A kinetic study of DNA and basic protein metabolism during spermatogenesis in the sand crab, Emerita analoga.

Cytochemical and radioautographic techniques define and confirm a staging scheme for developing spermatids of the decapod crab, Emerita analoga. Quantitative photometric data demonstrate that developing spermatids lose a significant proportion of their nuclear proteins, as evidenced by diminishing binding of fluorodinitrobenzene. Photometric results also show that much (but not all) of the spermatid nuclear protein loss is in somatic-type histone, as evidenced by a dramatic fall in the histone/DNA ratio of these cells during a period in which nuclear DNA content remains constant. By the end of spermiogenesis, the sperm nuclear histone and protamine content is approximately zero, whereas some nonbasic protein persists. Loss of spermatid nuclear somatic-type histone is not accompanied by synthesis of gamete-type histone (e.g. protamine or arginine-rich histone), showing that the processes of displacement and synthesis of nuclear basic proteins during histone transition are not subject to obligatory coupling. Labeling studies suggest that nonbasic acrosomal proteins (presumably partly enzymes) are synthesized in the cytoplasm, after which they move into the acrosome. Stainable basic proteins accumulate in the acrosome during precisely the period of nuclear somatic histone loss, suggesting nuclear-cytoplasmic transfer.

Molecular Cytogenetic Characterization of a Karyotype of a Female Patient with Secondary Amenorrhea with a Cell Line Showing 46,X,+mar.

OBJECTIVES: Disorders of sex development (DSD) include a group of conditions in which genotypes do not correlate with the typical male and female phenotypes. Numerical and structural abnormalities involving both autosomes and sex chromosomes have been observed in DSD. Specifically, deletions, duplications, and translocations involving specific genes as well as point mutations and less common aberrations have been implicated in the pathogenesis of these conditions. Finally, recent advances in analytical tools, namely chromosomal microarrays and sequencing methods, have greatly enhanced the precision with which DSD are genetically characterized and phenotypically correlated. Herein we report a case of a 24-year-old female patient who presented with secondary amenorrhea. Cytogenetic studies of her peripheral blood showed an abnormal clone with 45,X in three cells and the other was initially observed by chromosome analysis as 46,X,+mar in 27 cells. Molecular cytogenetics were performed to characterize the marker chromosome that showed two copies of the SRY, two copies of the heterochromatin Yq12, and two copies of the Y centromere Yp11.1-q11.1 on the marker chromosome, resulting in the identification of an isodicentric Y chromosome. Females with a 46,XY karyotype have gonadal dysgenesis and typically present as mosaic, along with a 45,X cell line. Some show small deletions of the short arm of the Y chromosome. Further studies based on the clinical picture, as well as possible prophylactic gonadectomy due to an increased risk of gonadal malignancy, gonadoblastoma or dysgerminoma, are suggested. Genetic counseling was recommended.

A mortality review of adult inpatients with tuberculosis in Mendi, Papua New Guinea.

SETTING: Mendi Provincial Hospital, Southern Highlands Province, Papua New Guinea (PNG). BACKGROUND: PNG is a high burden country for tuberculosis (TB) and TB-human immunodeficiency virus (HIV). TB is the second most common cause of death in PNG. OBJECTIVE: To identify the number of adult inpatients with TB who died between 1 January 2015 and 30 August 2017; describe these patients' characteristics and identify contributing factors that could be modified. DESIGN: This was a retrospective case series review. RESULTS: Among 905 inpatients with TB during the study period, there were 90 deaths. The patients who died were older than those who survived (median age 40 years vs. 32 years, P = 0.011). The majority of patients who died lived less than 3 hours from the hospital (71%), were diagnosed after admission (79%) and were clinically diagnosed (77%). HIV status was not known in 50% of the deaths. Of patients with a known status, 27% (12/45) were HIV-positive. The median symptom duration prior to presentation was 28 days, with females presenting later than males (84 vs. 28 days, P = 0.008). CONCLUSION: This study highlights areas where community and hospital-based management of TB could be improved to potentially reduce TB mortality, including earlier detection and treatment, improved bacteriological diagnosis and increased HIV testing.