Purpose Detecting signals of micrometastatic disease in patients with early breast cancer (EBC) could improve risk stratification and allow better tailoring of adjuvant therapies. We previously showed that postoperative serum metabolomic profiles were predictive of relapse in a single-center cohort of estrogen receptor (ER)–negative EBC patients. Here, we investigated this further using preoperative serum samples from ER-positive, pre-menopausal women with EBC who were enrolled in an international phase III trial. Experimental Design Proton nuclear magnetic resonance (NMR) spectroscopy of 590 EBC samples (319 with relapse or ≥6 years clinical follow-up) and 109 metastatic breast cancer (MBC) samples was performed. A Random Forest (RF) classification model was built using a training set of 85 EBC and all MBC samples. The model was then applied to a test set of 234 EBC samples, and a risk of recurrence score was generated on the basis of the likelihood of the sample being misclassified as metastatic. Results In the training set, the RF model separated EBC from MBC with a discrimination accuracy of 84.9%. In the test set, the RF recurrence risk score correlated with relapse, with an AUC of 0.747 in ROC analysis. Accuracy was maximized at 71.3% (sensitivity, 70.8%; specificity, 71.4%). The model performed independently of age, tumor size, grade, HER2 status and nodal status, and also of Adjuvant! Online risk of relapse score. Conclusions In a multicenter group of EBC patients, we developed a model based on preoperative serum metabolomic profiles that was prognostic for disease recurrence, independent of traditional clinicopathologic risk factors.

BackgroundBRAC, an indigenous non-governmental development organization (NGO), has been implementing a programme to prevent and control malaria in the 13 malaria-endemic districts of Bangladesh since 2007. One of the critical preventive interventions is the distribution of insecticidal bed nets (long-lasting insecticide-treated nets, LLINs and insecticide-treated ordinary nets, ITNs) to the community free of cost. This study aimed to assess progress in the possession, preferential use, and knowledge on use of the LLIN/ITNs including the programme's avowed pro-poor inclination one and three and half years after intervention began.MethodsA convenient sampling strategy based on malaria endemicity in the districts was adopted. First, thirty upazila (sub-district, with a population around 250,000)s were selected at random, with high prevalent districts contributing more upazilas; second, from each upazila, one (2008) to two (2011) villages (covered by insecticidal bed net distribution programme) were selected. From each village, households that had either one under-five child and/or a pregnant woman were included in the survey, one household being included only once. Data were collected using a pre-tested structured questionnaire.ResultsIn all, 3,760 households in 2008 and 7,895 households in 2011 were surveyed for collecting relevant information. Proportion of households with at least one LLIN, and at least one LLIN/ITN increased (22-59 to 62-67% and 22-64% to 74-76% respectively) over time, including increase in the mean number of LLIN/ITNs per household (≤ 1 to 1 +). The programme achieved > 80% coverage in sleeping under an LLIN/ITN in the case of under-five children and pregnant women, especially in the high-endemic districts. Knowledge regarding critical time of hanging the net also increased over time (7-22 to 44-54%), but remained low. The pro-poor inclination of the programme is reflected in the status of relevant indicators according to self-rated poverty status of the households.ConclusionsThere has been a substantial improvement in possession and usage of insecticidal bed nets especially for the two most vulnerable groups (under-five children and pregnant women), including a reduction of gaps between the high and low endemic districts, and the deficit and non-deficit households during the study period.

1 Recent evidence from studies in mice lacking the opioid receptor-like (ORL-1) receptor and from experiments using antibodies raised against orphanin FQ/nociceptin (OFQ/N) suggest that this peptide may be involved in morphine tolerance. In the present study we sought to investigate if administration of exogenous OFQ/N would modulate the development of tolerance to the antinociceptive eect of morphine. 2 Rats were treated for 3 days with either saline or morphine (10 mg kg 71 , s.c.) followed, 15 and 75 min later, by two intracerebroventricular injections of either arti®cial cerebrospinal¯uid (aCSF) or OFQ/N. The dose of OFQ/N was doubled each day (7.5, 15, 30 nmol). On day 4, rats were tested on a hot plate apparatus before and 30, 60 and 90 min after morphine administration. 3 Repeated OFQ/N treatment did not aect basal nociceptive responses or morphine-induced antinociception. However, the same treatment signi®cantly attenuated the development of morphine tolerance. 4 Since learning and memory could contribute to the development of morphine tolerance, in subsequent studies, we examined the eect of OFQ/N administered in the CA3 region of the hippocampus, where OFQ/N has been shown to block LTP and impair spatial memory. A greater attenuation of morphine tolerance with no alteration of baseline hot plate latency or morphineinduced antinociception was observed when OFQ/N was administered in this area of the rat brain. 5 Taken together, our results demonstrate that OFQ/N may act in the hippocampus to attenuate morphine tolerance.

Background Nationally representative data on burden of musculoskeletal conditions (MSK) in Bangladesh are not available. The objective of this study was to determine the prevalence of MSK conditions and related disabilities in the adult population of Bangladesh. Methods A total of 2000 individuals aged 18 years or older were targeted from 20 primary sampling units (urban and rural) of all former seven divisions of Bangladesh in 2015. Structured interviews were done using the modified Community Oriented Program for Control of Rheumatic Disorders questionnaire to detect positive respondents. Standard criteria were used for diagnosing MSK conditions by rheumatology residents. In case of uncertainty, opinion was taken from senior rheumatologists. A Bangla version of the Health Assessment Questionnaire was used to determine disability. Results A total of 1843 (92.1%) participated. Among them, 892 men and 951 women participated from rural (n = 716) and urban (n = 1127) areas. Their mean age was 40.5 (standard deviation 14.7) years. Almost a third did not have any formal schooling. Overall, 30.4% (95% confidence interval, 28.3–32.5) had MSK conditions. Low back pain (18.6%, 16.9–20.5), knee osteoarthritis (7.3%, 6.1–8.5) and soft tissue rheumatism 3.8% (2.9–4.7) were the three top-ranking MSK conditions. Rheumatoid arthritis (1.6%, 1.0–2.1), spondyloarthritis (1.2%, 7–1.8) and adhesive capsulitis (1.4%, 0.9–1.9) were relatively uncommon. Among those who had MSK conditions, 24.8% (21.3–28.6) had some degree of disability. Of them, 24.4% (21.0–28.1) had history of work loss during last 12 months. Conclusions The high burden of MSK conditions and related disabilities in Bangladesh warrants greater attention of the health system. Further studies are needed to estimate the impact of this group of conditions particularly addressing related disabilities and loss of work.

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