Cancer prevalence in 129 breast-ovarian cancer families tested for BRCA1 and BRCA2 mutations

Background. Women who carry germline mutations in the breast-ovarian cancer susceptibility genes, BRCA1 and BRCA2, are at very high risk of developing breast and/or ovarian cancer. Both genes are tumour suppressor genes that protect all cells from deregulation, and there are reports of their involvement in other cancers that vary and seem to depend on the population investigated. It is therefore important to investigate the other associated cancers in different populations to assist with risk assessments.Objectives. To assess the cancer risk profile in  RCA-mutationpositiveand negative South African breast-ovarian cancer families, mainly of Caucasian origin.Design. Descriptive study in which the prevalence of all cancers in the pedigrees of BRCA1- and BRCA2-mutationpositive groups and a group of families without mutations in either gene were compared with the general population.Results. As expected, female breast and ovarian cancer was significantly increased in all three groups. Furthermore, male breast cancer was significantly elevated in the BRCA2-positive and BRCA-negative groups. Stomach cancer prevalence was significantly elevated in the BRCA2-positive families compared with the general population.Conclusions. These results can be applied in estimation of cancer risks and may contribute to more comprehensive counselling of mutation-positive Caucasian breast and/or ovarian cancer families

The Role of Host Traits, Season and Group Size on Parasite Burdens in a Cooperative Mammal

The distribution of parasites among hosts is often characterised by a high degree of heterogeneity with a small number of hosts harbouring the majority of parasites. Such patterns of aggregation have been linked to variation in host exposure and susceptibility as well as parasite traits and environmental factors. Host exposure and susceptibility may differ with sexes, reproductive effort and group size. Furthermore, environmental factors may affect both the host and parasite directly and contribute to temporal heterogeneities in parasite loads. We investigated the contributions of host and parasite traits as well as season on parasite loads in highveld mole-rats (Cryptomys hottentotus pretoriae). This cooperative breeder exhibits a reproductive division of labour and animals live in colonies of varying sizes that procreate seasonally. Mole-rats were parasitised by lice, mites, cestodes and nematodes with mites (Androlaelaps sp.) and cestodes (Mathevotaenia sp.) being the dominant ecto- and endoparasites, respectively. Sex and reproductive status contributed little to the observed parasite prevalence and abundances possibly as a result of the shared burrow system. Clear seasonal patterns of parasite prevalence and abundance emerged with peaks in summer for mites and in winter for cestodes. Group size correlated negatively with mite abundance while it had no effect on cestode burdens and group membership affected infestation with both parasites. We propose that the mode of transmission as well as social factors constrain parasite propagation generating parasite patterns deviating from those commonly predicted

Spatial Sorting Drives Morphological Variation in the Invasive Bird, Acridotheris tristis

The speed of range expansion in many invasive species is often accelerating because individuals with stronger dispersal abilities are more likely to be found at the range front. This ‘spatial sorting’ of strong dispersers will drive the acceleration of range expansion. In this study, we test whether the process of spatial sorting is at work in an invasive bird population (Common myna, Acridotheris tristis) in South Africa. Specifically, we sampled individuals across its invasive range and compared morphometric measurements relevant and non-relevant to the dispersal ability. Besides testing for signals of spatial sorting, we further examined the effect of environmental factors on morphological variations. Our results showed that dispersal-relevant traits are significantly correlated with distance from the range core, with strong sexual dimorphism, indicative of sex-biased dispersal. Morphological variations were significant in wing and head traits of females, suggesting females as the primary dispersing sex. In contrast, traits not related to dispersal such as those associated with foraging showed no signs of spatial sorting but were significantly affected by environmental variables such as the vegetation and the intensity of urbanisation. When taken together, our results support the role of spatial sorting in facilitating the expansion of Common myna in South Africa despite its low propensity to disperse in the native range

A systematic review of task- shifting for HIV treatment and care in Africa

BACKGROUND: Shortages of human resources for health (HRH) have severely hampered the rollout of antiretroviral therapy (ART) in sub-Saharan Africa. Current rollout models are hospital- and physician-intensive. Task shifting, or delegating tasks performed by physicians to staff with lower-level qualifications, is considered a means of expanding rollout in resource-poor or HRH-limited settings. METHODS: We conducted a systematic literature review. Medline, the Cochrane library, the Social Science Citation Index, and the South African National Health Research Database were searched with the following terms: task shift*, balance of care, non-physician clinicians, substitute health care worker, community care givers, primary healthcare teams, cadres, and nurs* HIV. We mined bibliographies and corresponded with authors for further results. Grey literature was searched online, and conference proceedings searched for abstracts. RESULTS: We found 2960 articles, of which 84 were included in the core review. 51 reported outcomes, including research from 10 countries in sub-Saharan Africa. The most common intervention studied was the delegation of tasks (especially initiating and monitoring HAART) from doctors to nurses and other non-physician clinicians. Five studies showed increased access to HAART through expanded clinical capacity; two concluded task shifting is cost effective; 9 showed staff equal or better quality of care; studies on non-physician clinician agreement with physician decisions was mixed, with the majority showing good agreement. CONCLUSIONS: Task shifting is an effective strategy for addressing shortages of HRH in HIV treatment and care. Task shifting offers high-quality, cost-effective care to more patients than a physician-centered model. The main challenges to implementation include adequate and sustainable training, support and pay for staff in new roles, the integration of new members into healthcare teams, and the compliance of regulatory bodies. Task shifting should be considered for careful implementation where HRH shortages threaten rollout programmes

Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women

Background: Most $\textit{BRCA1}$ or $\textit{BRCA2}$ mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both $\textit{BRCA1}$ and $\textit{BRCA2}$ are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female $\textit{BRCA1/2}$ mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at $\textit{BRCA1}$ (SH1) or $\textit{BRCA2}$ (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; $p$ = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 ($p$ = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 ($p$ = 0.231), but was on average 4.5 years younger in TH than in SH2 ($p$ < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive ($p$ = 0.010) or progesterone receptor (PR) positive ($p$ = 0.013) than in SH1, but less likely to be ER positive ($p$ < 0.001) or PR positive ($p$ = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for $\textit{BRCA1}$ or $\textit{BRCA2}$ in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2.ACA and the CIMBA data management are funded by Cancer Research UK (C12292/A20861 and C12292/A11174). TRR was supported by R01-CA083855, R01-CA102776, and P50-CA083638. KLN, TMF, and SMD are supported by the Basser Research Center at the University of Pennsylvania. BP is supported by R01-CA112520. Cancer Research UK provided financial support for this work. ACA is a Senior Cancer Research UK Cancer Research Fellow. DFE is Cancer Research UK Principal Research Fellow. Tumor analysis was funded by STOP CANCER (to SJR). Study-specific acknowledgements are as provided in the manuscript

The Present and Future Role of Insect-Resistant Genetically Modified Maize in IPM

Commercial, genetically-modified (GM) maize was first planted in the United States (USA, 1996) and Canada (1997) but now is grown in 13 countries on a total of over 35 million hectares (\u3e24% of area worldwide). The first GM maize plants produced a Cry protein derived from the soil bacteriumBacillus thuringiensis (Bt), which made them resistant to European corn borer and other lepidopteran maize pests. New GM maize hybrids not only have resistance to lepidopteran pests but some have resistance to coleopteran pests and tolerance to specific herbicides. Growers are attracted to the Btmaize hybrids for their convenience and because of yield protection, reduced need for chemical insecticides, and improved grain quality. Yet, most growers worldwide still rely on traditional integrated pest management (IPM) methods to control maize pests. They must weigh the appeal of buying insect protection “in the bag” against questions regarding economics, environmental safety, and insect resistance management (IRM). Traditional management of maize insects and the opportunities and challenges presented by GM maize are considered as they relate to current and future insect-resistant products. Four countries, two that currently have commercialize Bt maize (USA and Spain) and two that do not (China and Kenya), are highlighted. As with other insect management tactics (e.g., insecticide use or tillage), GM maize should not be considered inherently compatible or incompatible with IPM. Rather, the effect of GM insect-resistance on maize IPM likely depends on how the technology is developed and used

Malaria in Africa: Vector Species' Niche Models and Relative Risk Maps

A central theoretical goal of epidemiology is the construction of spatial models of disease prevalence and risk, including maps for the potential spread of infectious disease. We provide three continent-wide maps representing the relative risk of malaria in Africa based on ecological niche models of vector species and risk analysis at a spatial resolution of 1 arc-minute (9 185 275 cells of approximately 4 sq km). Using a maximum entropy method we construct niche models for 10 malaria vector species based on species occurrence records since 1980, 19 climatic variables, altitude, and land cover data (in 14 classes). For seven vectors (Anopheles coustani, A. funestus, A. melas, A. merus, A. moucheti, A. nili, and A. paludis) these are the first published niche models. We predict that Central Africa has poor habitat for both A. arabiensis and A. gambiae, and that A. quadriannulatus and A. arabiensis have restricted habitats in Southern Africa as claimed by field experts in criticism of previous models. The results of the niche models are incorporated into three relative risk models which assume different ecological interactions between vector species. The “additive” model assumes no interaction; the “minimax” model assumes maximum relative risk due to any vector in a cell; and the “competitive exclusion” model assumes the relative risk that arises from the most suitable vector for a cell. All models include variable anthrophilicity of vectors and spatial variation in human population density. Relative risk maps are produced from these models. All models predict that human population density is the critical factor determining malaria risk. Our method of constructing relative risk maps is equally general. We discuss the limits of the relative risk maps reported here, and the additional data that are required for their improvement. The protocol developed here can be used for any other vector-borne disease

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

BackgroundHeight and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown.MethodsWe applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models.ResultsObserved height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction ConclusionOur observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population