Interactions between fur seals (Arctocephalus pusillus doriferus and A. forsteri) and tour boats at Montague Island were investigated between November 1997 and November 1998. The fur seals were in ...four haul-out sites, which are referred to here as colonies. The study was
instigated by the management requirement of the National Parks and Wildlife Service of New South Wales to determine effects of disturbance from tour boats on the fur seal colonies. At each of 84 inspections, distance between the boat and the colony was measured and seal behavior (or response)
was recorded 11 times at 15-second intervals as the boat moved toward the seals. This period of 2.5 minutes was approximately the time tour boats stayed at a colony. Behavior of the fur seals ashore was recorded in four categories of increasing disturbance from "Resting" to "Many moving."
From analyses using multinomial models, the probability of observing a given response by the fur seals and the pattern of the responses as a function of distance from the colony were both influenced by the colony under observation. In general, fur seals' responses were significantly correlated
with distance between the study boat and the colony, and with the size of the colony (i.e., number of fur seals visible ashore). In all cases, the probability of the colony remaining in the "Resting" category decreased as the distance between the colony and the study boat decreased. Similarly
the probability of the colony showing the maximum response ("Many moving") increased as the distance decreased. The probability of New Zealand fur seals "Resting" was higher than for Australian fur seals. Tour boats approaching the colonies had a relatively small effect on the fur seals; few
or none of them ran to the sea. Based on results from this study, we recommended that the minimum approach distance of tour boats to the fur seal colonies at Montague Island should be 40 m; other recommendations involved how tour boats approach the fur seal colonies. The former has been gazetted
as a government regulation and the other recommendations have been incorporated into the license conditions for the tour boats operators.
The increased incidence of diseases, including metabolic syndrome and infertility, may be related to exposure to the mixture of chemicals, which are ubiquitous in the modern environment ...(environmental chemicals, ECs). Xeno-detoxification occurs within the liver which is also the source of many plasma proteins and growth factors and plays an important role in the regulation of homeostasis.
The objective of this study was to investigate the effects of ECs on aspects of liver function, in a well characterized ovine model of exposure to a real-life EC mixture.
Four groups of sheep (n = 10–12/sex/treatment) were maintained long-term on control or sewage sludge-fertilized pastures: from conception to culling at 19 months of age in females and from conception to 7 months of age and thereafter in control plots until culling at 19 months of age in males. Environmental chemicals were measured in sheep livers and RNA and protein extracts were assessed for exposure markers. Liver proteins were resolved using 2D differential in-gel electrophoresis and differentially expressed protein spots were identified by liquid chromatography/tandem mass spectroscopy.
Higher levels of polycyclic aromatic hydrocarbons (PAHs) and lower levels of polychlorinated biphenyls (PCBs) in the livers of control males compared to control females indicated sexually dimorphic EC body burdens. Increased levels of the PAHs Benzoaanthracene and chrysene and reduced levels of PCB 153 and PCB 180 were observed in the livers of continuously exposed females. EC exposure affected xenobiotic and detoxification responses and the liver proteome in both sexes and included major plasma-secreted and blood proteins, and metabolic enzymes whose pathway analysis predicted dysregulation of cancer-related pathways and altered lipid dynamics. The latter were confirmed by a reduction in total lipids in female livers and up-regulation of cancer-related transcript markers in male livers respectively by sewage sludge exposure.
Our results demonstrate that chronic exposure to ECs causes major physiological changes in the liver, likely to affect multiple systems in the body and which may predispose individuals to increased disease risks.
•Chronic exposure to environmental chemicals affects liver physiology.•Proteomic measurements showed widespread dysregulation in the exposed livers.•Exposure dysregulated important plasma proteins such as albumin and transferrin•Reduction in total lipids in the exposed female livers•Increase in cancer markers in the exposed male livers
The experiences of men in the immediate postoperative period following surgery for primary prostate cancer are well reported in the literature. Recognition of the unresolved morbidity encountered by ...men in the medium term suggests that a more complete understanding of how men cope in the long term is needed. Health professionals are deserving of a more complete literature for the purpose of providing holistic care for this group of men, providing informed advocacy and better support for men living with the diagnosis of prostate cancer. Emerging literature reveals that men's knowledge of the long term problems associated with prostatectomy was inadequate at the time they consented to treatment; the likely outcomes at all phases of recovery should be taken into account when deciding on choice of treatment or no treatment.
This qualitative study aims to describe men's long term recovery following prostatectomy for the purpose identifying the effects of unresolved post surgical morbidity. The content analysis of focus group interviews revealed that incontinence and impotence were a major source of emotional tension affecting the men's social interactions and sense of self-worth. The men expressed great regret over the lack of information accessible to them for evaluating the risk and nature of long term problems. The thick description provided in this study identifies the need for empathetic assessment of men with ongoing post surgical issues and alerts the reader to the inadequacies of information provided prior to consent to prostatectomy.
Summary Background To reduce lipid abnormalities and other side-effects associated with antiretroviral regimens containing lopinavir-ritonavir, patients might want to switch one or more components of ...their regimen. We compared substitution of raltegravir for lopinavir-ritonavir with continuation of lopinavir-ritonavir in HIV-infected patients with stable viral suppression on lopinavir-ritonavir-based combination therapy. Methods The SWITCHMRK 1 and 2 studies were multicentre, double-blind, double-dummy, phase 3, randomised controlled trials. HIV-infected patients aged 18 years or older were eligible if they had documented viral RNA (vRNA) concentration below the limit of assay quantification for at least 3 months while on a lopinavir-ritonavir-based regimen. 707 eligible patients were randomly allocated by interactive voice response system in a 1:1 ratio to switch from lopinavir-ritonavir to raltegravir (400 mg twice daily; n=353) or to remain on lopinavir-ritonavir (two 200 mg/50 mg tablets twice daily; n=354), while continuing background therapy consisting of at least two nucleoside or nucleotide reverse transcriptase inhibitors. Primary endpoints were the mean percentage change in serum lipid concentrations from baseline to week 12; the proportion of patients with vRNA concentration less than 50 copies per mL at week 24 (with all treated patients who did not complete the study counted as failures) with a prespecified non-inferiority margin of −12% for each study; and the frequency of adverse events up to 24 weeks. Analyses were done according to protocol. These trials are registered with ClinicalTrials.gov , numbers NCT00443703 and NCT00443729. Findings 702 patients received at least one dose of study drug and were included in the efficacy and safety analyses for the combined trials (raltegravir, n=350; lopinavir-ritonavir, n=352). Percentage changes in lipid concentrations from baseline to week 12 were significantly greater (p<0·0001) in the raltegravir group than in the lopinavir-ritonavir group in each study, yielding combined results for total cholesterol −12·6% vs 1·0%, non-HDL cholesterol −15·0% vs 2·6%, and triglycerides −42·2% vs 6·2%. At week 24, 293 (84·4%, 95% CI 80·2–88·1) of 347 patients in the raltegravir group had vRNA concentration less than 50 copies per mL compared with 319 (90·6%, 87·1–93·5) of 352 patients in the lopinavir-ritonavir group (treatment difference −6·2%, −11·2 to −1·3). Clinical and laboratory adverse events occurred at similar frequencies in the treatment groups. There were no serious drug-related adverse events or deaths. The only drug-related clinical adverse event of moderate to severe intensity reported in 1% or more of either treatment group was diarrhoea, which occurred in ten patients in the lopinavir-ritonavir group (3%) and no patients in the raltegravir group. The studies were terminated at week 24 because of lower than expected virological efficacy in the raltegravir group compared with the lopinavir-ritonavir group. Interpretation Although switching to raltegravir was associated with greater reductions in serum lipid concentrations than was continuation of lopinavir-ritonavir, efficacy results did not establish non-inferiority of raltegravir to lopinavir-ritonavir. Funding Merck.
Germline missense variants of unknown significance in cancer-related genes are increasingly being identified with the expanding use of next-generation sequencing. The ataxia telangiectasia-mutated (
...) gene on chromosome 11 has more than 1,000 germline missense variants of unknown significance and is a tumor suppressor. We aimed to determine if rare germline
variants are more frequent in chronic lymphocytic leukemia (CLL) compared with other hematologic malignancies and if they influence the clinical characteristics of CLL.
We identified 3,128 patients (including 825 patients with CLL) in our hematologic malignancy clinic who had received clinical-grade sequencing of the entire coding region of
. We ascertained the comparative frequencies of germline
variants in categories of hematologic neoplasms, and, in patients with CLL, we determined whether these variants affected CLL-associated characteristics such as somatic 11q deletion.
Rare germline
variants are present in 24% of patients with CLL, significantly greater than that in patients with other lymphoid malignancies (16% prevalence), myeloid disease (15%), or no hematologic neoplasm (14%). Patients with CLL with germline
variants are younger at diagnosis and twice as likely to have 11q deletion. The
variant p.L2307F is present in 3% of patients with CLL, is associated with a three-fold increase in rates of somatic 11q deletion, and is a hypomorph in cell-based assays.
Germline
variants cluster within CLL and affect the phenotype of CLL that develops, implying that some of these variants (such as
p.L2307F) have functional significance and should not be ignored. Further studies are needed to determine whether these variants affect the response to therapy or account for some of the inherited risk of CLL.
The Mid-InfraRed Instrument (MIRI) on the James Webb Space Telescope (JWST) provides measurements over the wavelength range 5 to 28.5 μm. MIRI has, within a single "package," four key scientific ...functions: photometric imaging, coronagraphy, single-source low-spectral resolving power (R ∼ 100) spectroscopy, and medium-resolving power (R ∼ 1500 to 3500) integral field spectroscopy. An associated cooler system maintains MIRI at its operating temperature of < 6.7 K. This paper describes the driving principles behind the design of MIRI, the primary design parameters, and their realization in terms of the "as-built" instrument. It also describes the test program that led to delivery of the tested and calibrated Flight Model to NASA in 2012, and the confirmation after delivery of the key interface requirements.
ABSTRACT
Cancer risk is determined by a complex interplay of genetic and environmental factors. Genome‐wide association studies (GWAS) have identified hundreds of common (minor allele frequency MAF > ...0.05) and less common (0.01 < MAF < 0.05) genetic variants associated with cancer. The marginal effects of most of these variants have been small (odds ratios: 1.1–1.4). There remain unanswered questions on how best to incorporate the joint effects of genes and environment, including gene‐environment (G × E) interactions, into epidemiologic studies of cancer. To help address these questions, and to better inform research priorities and allocation of resources, the National Cancer Institute sponsored a “Gene‐Environment Think Tank” on January 10–11, 2012. The objective of the Think Tank was to facilitate discussions on (1) the state of the science, (2) the goals of G × E interaction studies in cancer epidemiology, and (3) opportunities for developing novel study designs and analysis tools. This report summarizes the Think Tank discussion, with a focus on contemporary approaches to the analysis of G × E interactions. Selecting the appropriate methods requires first identifying the relevant scientific question and rationale, with an important distinction made between analyses aiming to characterize the joint effects of putative or established genetic and environmental factors and analyses aiming to discover novel risk factors or novel interaction effects. Other discussion items include measurement error, statistical power, significance, and replication. Additional designs, exposure assessments, and analytical approaches need to be considered as we move from the current small number of success stories to a fuller understanding of the interplay of genetic and environmental factors.
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