Characteristics and early outcomes of cervical cancer patients at Butaro District Hospital, Rwanda: a retrospective review

Background: Cancer treatment facilities are scarce in rural areas of low-income and middle-income countries, where the highest burden of cervical cancer exists. The Butaro Cancer Center of Excellence (BCCOE), in rural Rwanda, is a Rwandan Ministry of Health facility supported by Partners In Health and Dana-Farber/Brigham and Women's Cancer Center. The cervical cancer programme includes diagnosis, staging, and treatment. However, because of resource limitations, only 15 patients per month could be referred for radiotherapy to the Uganda Cancer Institute. In this study, we describe cervical cancer treatment at BCCOE and early patient outcomes. Methods: In July, 2016, we retrospectively reviewed records for patients with cervical cancer enrolled between July 1, 2012, and June 30, 2015, at BCCOE. We extracted data on patients' characteristics, disease stage, treatment, and outcomes. Findings: We included 438 patients: median age was 52 years (IQR 42–60 years), 35 patients (8%) had laboratory-confirmed HIV, 142 (36%) smoked tobacco, median number of pregnancies was 7 (IQR 5–9), and 41 (10%) had had a hysterectomy before enrolment. 258 patients (60%) had a diagnosis confirmed by pathology, and 391 patients (91%) had a documented disease stage. Of these, 13 (3%) were Stage I, 183 (47%) were Stage II, 154 (39%) were Stage-III, and 41 (11%) were Stage IV. There was a curative, instead of palliative or undecided, intent for 85% of Stage I patients, 91% of Stage II, and, 12% of Stage III. 165 women (38%) were referred for concurrent radiation therapy, chemotherapy, and brachytherapy in Uganda, and 19 (4%) were referred for radical hysterectomy. At their last recorded visit, 77 patients (18%) had no evidence of recurrence, including: 6 (46%) Stage I patients, 66 (37%) Stage II, 5 (3%) Stage III, but no Stage IV patients (p =<0·0001). Overall, 114 patients (27%) were lost to follow-up during or after treatment. Interpretation: Our experience shows that a cervical cancer treatment programme is viable in a low-resource, rural setting. However, many challenges exist, especially the severity of disease at intake (about half of patients presented with Stage III or IV disease) and that there are no radiation facilities in Rwanda. Further, a quarter of patients were eventually lost to follow-up during the study. Future implementation interventions will focus on strategies to overcome these challenges. Funding: Partners in Health, Dana-Farber Cancer Institute, Rwandan Ministry of Health

Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants

Searches for R-parity-violating supersymmetry in pp collisions at s=8\sqrt{s} = 8 TeV in final states with 0-4 leptons

Results are presented from searches for R-parity-violating supersymmetry in events produced in pp collisions at sqrt(s)=8 TeV at the LHC. Final states with 0, 1, 2, or multiple leptons are considered independently. The analysis is performed on data collected by the CMS experiment corresponding to an integrated luminosity of 19.5 inverse femtobarns. No excesses of events above the standard model expectations are observed, and 95% confidence level limits are set on supersymmetric particle masses and production cross sections. The results are interpreted in models featuring R-parity-violating decays of the lightest supersymmetric particle, which in the studied scenarios can be either the gluino, a bottom squark, or a neutralino. In a gluino pair production model with baryon number violation, gluinos with a mass less than 0.98 and 1.03 TeV are excluded, by analyses in a fully hadronic and one-lepton final state, respectively. An analysis in a dilepton final state is used to exclude bottom squarks with masses less than 307 GeV in a model considering bottom squark pair production. Multilepton final states are considered in the context of either strong or electroweak production of superpartners, and are used to set limits on the masses of the lightest supersymmetric particles. These limits range from 300 to 900 GeV in models with leptonic and up to approximately 700 GeV in models with semileptonic R-parity-violating couplings

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

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Genetic studies of body mass index yield new insights for obesity biology

Note: A full list of authors and affiliations appears at the end of the article. Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p