Pulsatile luteinizing hormone disruption in depression

Two independent groups recently published data comparing pulsatile luteinizing hormone (LH) release between depressed and control women. Despite similar populations and LH sampling frequency, they reached different conclusions: Meller et al. [Am. J. Psych. 154 (1997) 1454] found disruption of normal LH pulsatility in depressed women, whereas Young et al. [Arch. Gen. Psych. 57 (2000) 1157] did not. To resolve this discrepancy, the current study applies a single, well-established statistical method, spectral analysis, to the two data sets and concludes that both depressed populations display significantly altered LH pulsatile release.NIMH MH50030Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49487/2/YoungandGrambsch.pd

Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.

BACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART

Predicting fitness to practise events in international medical graduates who registered as UK doctors via the Professional and Linguistic Assessments Board (PLAB) system: a national cohort study

Background International medical graduates working in the UK are more likely to be censured in relation to fitness to practise compared to home graduates. Performance on the General Medical Council’s (GMC’s) Professional and Linguistic Assessments Board (PLAB) tests and English fluency have previously been shown to predict later educational performance in this group of doctors. It is unknown whether the PLAB system is also a valid predictor of unprofessional behaviour and malpractice. The findings would have implications for regulatory policy. Methods This was an observational study linking data relating to fitness to practise events (referral or censure), PLAB performance, demographic variables and English language competence, as evaluated via the International English Language Test System (IELTS). Data from 27,330 international medical graduates registered with the GMC were analysed, including 210 doctors who had been sanctioned in relation to at least one fitness to practise issue. The main outcome was risk of eventual censure (including a warning). Results The significant univariable educational predictors of eventual censure (versus no censures or referrals) were lower PLAB part 1 (hazard ratio [HR], 0.99; 95% confidence interval, 0.98 to 1.00) and part 2 scores (HR, 0.94; 0.91 to 0.97) at first sitting, multiple attempts at both parts of the PLAB, lower IELTS reading (HR, 0.79; 0.65 to 0.94) and listening scores (HR, 0.76; 0.62 to 0.93) and higher IELTS speaking scores (HR, 1.28; 1.04 to 1.57). Multiple resits at either part of the PLAB and higher IELTS speaking score (HR, 1.49; 1.20 to 1.84) were also independent predictors of censure. We estimated that the proposed limit of four attempts at both parts of the PLAB would reduce the risk in this entire group by only approximately two censures per 5 years in this group of doctors. Conclusions Making the PLAB, or any replacement assessment, more stringent and raising the required standards of English reading and listening may result in fewer fitness to practice events in international medical graduates. However, the number of PLAB resits permitted would have to be further capped to meaningfully impact the risk of sanctions in this group of doctor

Vascular endothelial growth factor in node-positive breast cancer patients treated with adjuvant tamoxifen

In 212 postmenopausal women with node-positive oestrogen receptor-positive (ER(LBA)) breast cancer subjected to radical surgery and adjuvant tamoxifen, the risk of 6-year relapse increased with increasing values of intratumoral vascular endothelial growth factor (VEGF) in patients whose tumours had a low/intermediate ER(LBA) content compared to patients with high-ER(LBA) tumours. These findings indicate that tumour progression, activated or sustained by high VEGF levels, may be counteracted in high-ER(LBA) cancers by tamoxifen, which in contrast fails to contrast the metastatic potential in low-ER(LBA) tumours

Optimal Patch-Leaving Behaviour: A Case Study Using The Parasitoid Cotesia rebecula

1. Parasitoids are predicted to spend longer in patches with more hosts, but previous work on Cotesia rubecula (Marshall) has not upheld this prediction. Tests of theoretical predictions may be affected by the definition of patch leaving behaviour, which is often ambiguous. 2. In this study whole plants were considered as patches and assumed that wasps move within patches by means of walking or flying. Within-patch and between-patch flights were distinguished based on flight distance. The quality of this classification was tested statistically by examination of log-survivor curves of flight times. 3. Wasps remained longer in patches with higher host densities, which is consistent with predictions of the marginal value theorem (Charnov 1976). Under the assumption that each flight indicates a patch departure, there is no relationship between host density and leaving tendency. 4. Oviposition influences the patch leaving behaviour of wasps in a count down fashion (Driessen et al. 1995), as predicted by an optimal foraging model (Tenhumberg, Keller & Possingham 2001). 5. Wasps spend significantly longer in the first patch encountered following release, resulting in an increased rate of superparasitism

Lower age at menarche affects survival in older Australian women: results from the Australian Longitudinal Study of Ageing

Extent: 10p.Background: While menarche indicates the beginning of a woman's reproductive life, relatively little is known about the association between age at menarche and subsequent morbidity and mortality. We aimed to examine the effect of lower age at menarche on all-cause mortality in older Australian women over 15 years of follow-up. Methods: Data were drawn from the Australian Longitudinal Study of Ageing (n = 1,031 women aged 65-103 years). We estimated the hazard ratio (HR) associated with lower age at menarche using Cox proportional hazards models, and adjusted for a broad range of reproductive, demographic, health and lifestyle covariates. Results: During the follow-up period, 673 women (65%) died (average 7.3 years (SD 4.1) of follow-up for decedents). Women with menses onset < 12 years of age (10.7%; n = 106) had an increased hazard of death over the follow-up period (adjusted HR 1.28; 95%CI 0.99-1.65) compared with women who began menstruating aged ≥ 12 years (89.3%; n = 883). However, when age at menarche was considered as a continuous variable, the adjusted HRs associated with the linear and quadratic terms for age at menarche were not statistically significant at a 5% level of significance (linear HR 0.76; 95%CI 0.56 - 1.04; quadratic HR 1.01; 95%CI 1.00-1.02). Conclusion: Women with lower age at menarche may have reduced survival into old age. These results lend support to the known associations between earlier menarche and risk of metabolic disease in early adulthood. Strategies to minimise earlier menarche, such as promoting healthy weights and minimising family dysfunction during childhood, may also have positive longer-term effects on survival in later life.Lynne C Giles, Gary FV Glonek, Vivienne M Moore, Michael J Davies and Mary A Luszc

Seasonal cycles enhance disparities between low- and high-income countries in exposure to monthly temperature emergence with future warming

A common proxy for the adaptive capacity of a community to the impacts of future climate change is the range of climate variability which they have experienced in the recent past. This study presents an interpretation of such a framework for monthly temperatures. Our results demonstrate that emergence into genuinely 'unfamiliar' climates will occur across nearly all months of the year for low-income nations by the second half of the 21st century under an RCP8.5 warming scenario. However, high income countries commonly experience a large seasonal cycle, owing to their position in the middle latitudes: as a consequence, temperature emergence for transitional months translates only to more-frequent occurrences of heat historically associated with the summertime. Projections beyond 2050 also show low-income countries will experience 2–10 months per year warmer than the hottest month experienced in recent memory, while high-income countries will witness between 1–4 months per year hotter than any month previously experienced. While both results represent significant departures that may bring substantive societal impacts if greenhouse gas emissions continue unabated, they also demonstrate that spatial patterns of emergence will compound existing differences between high and low income populations, in terms of their capacity to adapt to unprecedented future temperatures

Cyclophosphamide- metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study

Abstract Introduction Cyclophosphamide-based adjuvant chemotherapy is a mainstay of treatment for women with node-positive breast cancer, but is not universally effective in preventing recurrence. Pharmacogenetic variability in drug metabolism is one possible mechanism of treatment failure. We hypothesize that functional single nucleotide polymorphisms (SNPs) in drug metabolizing enzymes (DMEs) that activate (CYPs) or metabolize (GSTs) cyclophosphamide account for some of the observed variability in disease outcomes. Methods We performed a retrospective cohort study of 350 women enrolled in a multicenter, randomized, adjuvant breast cancer chemotherapy trial (ECOG-2190/INT-0121). Subjects in this trial received standard-dose cyclophosphamide, doxorubicin and fluorouracil (CAF), followed by either observation or high-dose cyclophosphamide and thiotepa with stem cell rescue. We used bone marrow stem cell-derived genomic DNA from archival specimens to genotype CYP2B6, CYP2C9, CYP2D6, CYP3A4, CYP3A5, GSTM1, GSTT1, and GSTP1. Cox regression models were computed to determine associations between genotypes (individually or in combination) and disease-free survival (DFS) or overall survival (OS), adjusting for confounding clinical variables. Results In the full multivariable analysis, women with at least one CYP3A4 *1B variant allele had significantly worse DFS than those who were wild-type *1A/*1A (multivariate hazard ratio 2.79; 95% CI 1.52, 5.14). CYP2D6 genotype did not impact this association among patients with estrogen receptor (ER) -positive tumors scheduled to receive tamoxifen. Conclusions These data support the hypothesis that genetic variability in cyclophosphamide metabolism independently impacts outcome from adjuvant chemotherapy for breast cancer