Over recent years, it became widely accepted that alternative, renewable energy may come at some risk for wildlife, for example, when wind turbines cause large numbers of bat fatalities. To better ...assess likely populations effects of wind turbine related wildlife fatalities, we studied the geographical origin of the most common bat species found dead below German wind turbines, the noctule bat (Nyctalus noctula). We measured stable isotope ratios of non-exchangeable hydrogen in fur keratin to separate migrants from local individuals, used a linear mixed-effects model to identify temporal, spatial and biological factors explaining the variance in measured stable isotope ratios and determined the geographical breeding provenance of killed migrants using isoscape origin models. We found that 72% of noctule bat casualties (n = 136) were of local origin, while 28% were long-distance migrants. These findings highlight that bat fatalities at German wind turbines may affect both local and distant populations. Our results indicated a sex and age-specific vulnerability of bats towards lethal accidents at turbines, i.e. a relatively high proportion of killed females were recorded among migratory individuals, whereas more juveniles than adults were recorded among killed bats of local origin. Migratory noctule bats were found to originate from distant populations in the Northeastern parts of Europe. The large catchment areas of German wind turbines and high vulnerability of female and juvenile noctule bats call for immediate action to reduce the negative cross-boundary effects of bat fatalities at wind turbines on local and distant populations. Further, our study highlights the importance of implementing effective mitigation measures and developing species and scale-specific conservation approaches on both national and international levels to protect source populations of bats. The efficacy of local compensatory measures appears doubtful, at least for migrant noctule bats, considering the large geographical catchment areas of German wind turbines for this species.
Abstract Predictive biomarkers are essential for personalized medicine since they select the best treatment for a specific patient. However, of all biomarkers that are evaluated, only few are ...eventually used in clinical practice. Many promising biomarkers may be erroneously abandoned because they are investigated in small studies using standard statistical techniques which can cause small sample bias or lack of power. The standard technique for failure time endpoints is Cox proportional hazards regression with a multiplicative interaction term between binary variables of biomarker and treatment. Properties of this model in small studies have not been evaluated so far, therefore we performed a simulation study to understand its small sample behavior. As a remedy, we applied a Firth correction to the score function of the Cox model and obtained confidence intervals (CI) using a profile likelihood (PL) approach. These methods are generally recommended for small studies of different design. Our results show that a Cox model estimates the biomarker-treatment interaction term and the treatment effect in one of the biomarker subgroups with bias, and overestimates their standard errors. Bias is however reduced and power is increased with Firth correction and PL CIs. Hence, the modified Cox model and PL CI should be used instead of a standard Cox model with Wald based CI in small studies of predictive biomarkers.
Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the ...outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy.
The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up.
If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival.
The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.
pathotypes (i.e., enteropathogenic and enterotoxigenic) have been identified among the pathogens most responsible for moderate-to-severe diarrhea in low- and middle-income countries (LMICs). ...Pathogenic
are transmitted from infected human or animal feces to new susceptible hosts via environmental reservoirs such as hands, water, and soil. Commensal
, which includes nonpathogenic
strains, are widely used as fecal bacteria indicator, with their presence associated with increased likelihood of enteric pathogens and/or diarrheal disease. In this study, we investigated
contamination in environmental reservoirs within households (
= 142) in high-population density communities of Harare, Zimbabwe. We further assessed the interconnectedness of the environmental compartments by investigating associations between, and household-level risk factors for,
contamination. From the data we collected, the source and risk factors for
contamination are not readily apparent. One notable exception is the presence of running tap water on the household plot, which is associated with significantly less
contamination of drinking water, handwashing water, and hands after handwashing. In addition,
levels on hands after washing are significantly associated with handwashing water contamination, hand contamination before washing, and diarrhea incidence. Finally, we observed that animal ownership increases
contamination in soil, and
in soil are correlated with contamination on hands before washing. This study highlights the complexity of
contamination in household environments within LMICs. More, larger, studies are needed to better identify sources and exposure pathways of
-and enteric pathogens generally-to identify effective interventions.
Transcranial electric stimulation (TES) is an emerging technique, developed to non-invasively modulate brain function. However, the spatiotemporal distribution of the intracranial electric fields ...induced by TES remains poorly understood. In particular, it is unclear how much current actually reaches the brain, and how it distributes across the brain. Lack of this basic information precludes a firm mechanistic understanding of TES effects. In this study we directly measure the spatial and temporal characteristics of the electric field generated by TES using stereotactic EEG (s-EEG) electrode arrays implanted in cebus monkeys and surgical epilepsy patients. We found a small frequency dependent decrease (10%) in magnitudes of TES induced potentials and negligible phase shifts over space. Electric field strengths were strongest in superficial brain regions with maximum values of about 0.5 mV/mm. Our results provide crucial information of the underlying biophysics in TES applications in humans and the optimization and design of TES stimulation protocols. In addition, our findings have broad implications concerning electric field propagation in non-invasive recording techniques such as EEG/MEG.
Many scientific papers are published each year and substantial resources are spent to develop biomarker-based tests for precision oncology. However, only a handful of tests is currently used in daily ...clinical practice, since development is challenging. In this situation, the application of adequate statistical methods is essential, but little is known about the scope of methods used.
A PubMed search identified clinical studies among women with breast cancer comparing at least two different treatment groups, one of which chemotherapy or endocrine treatment, by levels of at least one biomarker. Studies presenting original data published in 2019 in one of 15 selected journals were eligible for this review. Clinical and statistical characteristics were extracted by three reviewers and a selection of characteristics for each study was reported.
Of 164 studies identified by the query, 31 were eligible. Over 70 different biomarkers were evaluated. Twenty-two studies (71%) evaluated multiplicative interaction between treatment and biomarker. Twenty-eight studies (90%) evaluated either the treatment effect in biomarker subgroups or the biomarker effect in treatment subgroups. Eight studies (26%) reported results for one predictive biomarker analysis, while the majority performed multiple evaluations, either for several biomarkers, outcomes and/or subpopulations. Twenty-one studies (68%) claimed to have found significant differences in treatment effects by biomarker level. Fourteen studies (45%) mentioned that the study was not designed to evaluate treatment effect heterogeneity.
Most studies evaluated treatment heterogeneity via separate analyses of biomarker-specific treatment effects and/or multiplicative interaction analysis. There is a need for the application of more efficient statistical methods to evaluate treatment heterogeneity in clinical studies.
Distal pancreatectomy (DP) is increasingly done by laparoscopy but data from routine practise are scarce. We describe practise in a national cohort.
Data from the Norwegian Patient Register of all ...patients undergoing DP from 2012 to 2016. National resection rates were analysed. Short-term outcomes include length of stay, reoperation, readmissions and 90-day mortality. Risk is reported as odds ratio (OR) with 95% confidence interval (c.i.).
Of 554 procedures, 327 (59%) were laparoscopic. Median age was 66 years (iqr 55–72) and 52% were women. Resection rates increased during the period for all DP (from 1.76 to 2.39 per 100.000/yr), and significantly for laparoscopic DP (adjusted R-square 0.858; P = 0.015). Elderly patients had more resection (r2 = 0.11; P = 0.019). Splenectomy (n = 427; 77%) was less likely with laparoscopy (laparoscopy 72% vs open 84%, respectively; OR 0.64, 95% c.i. 0.42–0.97; P = 0.035). Multivisceral resections occurred more often in open DP (5.3% vs 1.2% for laparoscopy, OR 4.51, 1.44–14.2; P = 0.008). Reoperation occurred in 34 (6%), readmission in 109 (20%), and mortality in 8 (1.4%). Hospital stay was shorter for laparoscopic DP.
Use of DP increases in the population, particularly in the elderly, with use of laparoscopic access and an association with a reduced hospital stay.
The 70‐gene signature (MammaPrint™) has been developed on retrospective series of breast cancer patients to predict the risk of breast cancer distant metastases. The ...microarRAy‐prognoSTics‐in‐breast‐cancER (RASTER) study was the first study designed to prospectively evaluate the performance of the 70‐gene signature, which result was available for 427 patients (cT1–3N0M0). Adjuvant systemic treatment decisions were based on the Dutch CBO 2004 guidelines, the 70‐gene signature and doctors' and patients' preferences. Five‐year distant‐recurrence‐free‐interval (DRFI) probabilities were compared between subgroups based on the 70‐gene signature and Adjuvant! Online (AOL) (10‐year survival probability <90% was defined as high‐risk). Median follow‐up was 61.6 months. Fifteen percent (33/219) of the 70‐gene signature low‐risk patients received adjuvant chemotherapy (ACT) versus 81% (169/208) of the 70‐gene signature high‐risk patients. The 5‐year DRFI probabilities for 70‐gene signature low‐risk (n = 219) and high‐risk (n = 208) patients were 97.0% and 91.7%. The 5‐year DRFI probabilities for AOL low‐risk (n = 132) and high‐risk (n = 295) patients were 96.7% and 93.4%. For 70‐gene signature low‐risk–AOL high‐risk patients (n = 124), of whom 76% (n = 94) had not received ACT, 5‐year DRFI was 98.4%. In the AOL high‐risk group, 32% (94/295) less patients would be eligible to receive ACT if the 70‐gene signature was used. In this prospective community‐based observational study, the 5‐year DRFI probabilities confirmed the additional prognostic value of the 70‐gene signature to clinicopathological risk estimations such as AOL. Omission of adjuvant chemotherapy as judged appropriate by doctors and patients and instigated by a low‐risk 70‐gene signature result, appeared not to compromise outcome.
What's new?
The “MammaPrint” is a 70‐gene signature developed to predict the risk of breast cancer metastases. This study, the RASTER study, provides the first prospective data looking at this 70‐gene signature to evaluate it's performance. For 427 patients, treatment decisions were based on standard guidelines, the 70‐gene signature, and doctors' and patients' preferences. Here, 124 patients were categorized as “low‐risk” by the 70‐gene signature, but high‐risk by other measures, such as age, tumor size, nodal status, and other clinicopathological factors. Of these, 76% did not receive adjuvant chemotherapy, and 98% survived 5 years with no recurrence of disease. Thus, withholding chemotherapy based on the low‐risk gene signature result, and in accordance with doctors' and patients' preferences, did not negatively impact recurrence rate, confirming the prognostic value of this new tool.
Greater understanding of the biology of triple-negative breast cancer (TNBC) is needed to discern the roughly 60% of node-negative patients who are already cured with locoregional therapy from the ...40% who need adjuvant systemic therapy to be cured. Recent evidence suggests that patients with TNBC whose tumours have an activated immune response gene signature have a more favourable outcome than TNBC patients without this signature. For the group who needs additional systemic therapy, the challenge remains to choose the right systemic drug combination for the right TNBC sub-type. Significant heterogeneity exists within the TNBC class that is exemplified by differing chemotherapeutic sensitivity observed for some sub-types. This heterogeneity establishes the need for identifying differentiating molecular markers within the overall class of TNBC disease, which may help refine therapeutic management. In this review, we discuss some of these promising predictive molecular markers for tailoring therapy. In addition, several gene expression profiling and functional studies employing genetic screens that help to establish TNBC sub-groups with varying sensitivities to a variety of targeted therapies currently under clinical investigation are conferred. It is anticipated that a greater understanding of the biology of TNBC and its complex heterogeneity will reveal novel targets or identify markers around which clinical trials in molecularly well-defined sub-groups can be designed.
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