Efficacy of adjuvant chemotherapy according to hormone receptor status in young patients with breast cancer: a pooled analysis

Introduction Breast cancer at a young age is associated with an unfavorable prognosis. Very young patients with breast cancer therefore are advised to undergo adjuvant chemotherapy irrespective of tumor stage or grade. However, chemotherapy alone may not be adequate in young patients with hormone receptor-positive breast cancer. Therefore, we studied the effect of adjuvant chemotherapy in young patients with breast cancer in relation to hormone receptor status. Methods Paraffin-embedded tumor material was collected from 480 early-stage breast cancer patients younger than 41 years who participated in one of four European Organization for Research and Treatment of Cancer trials. Using immunohistochemistry on the whole series of tumors, we assessed estrogen receptor (ER) status and progesterone receptor (PgR) status in a standardized way. Endpoints in this study were overall survival (OS) and distant metastasis-free survival (DMFS). The median follow-up period was 7.3 years. Results Overall, patients with ER-positive tumors had better OS rates (hazard ratio [HR] 0.63; P = 0.02) compared with those with ER-negative tumors. However, in the subgroup of patients who received chemotherapy, no significant difference in OS (HR 0.87; P = 0.63) and DMFS (HR 1.36; P = 0.23) was found between patients with ER-positive tumors or those with ER-negative tumors. These differences were similar for PgR status. Conclusion Young patients with hormone receptor-positive tumors benefit less from adjuvant systemic chemotherapy than patients with hormone receptor-negative tumors. These results confirm that chemotherapy alone cannot be considered optimal adjuvant systemic treatment in breast cancer patients 40 years old or younger with hormone receptor-positive tumors

Is visual estimation of passive range of motion in the pediatric lower limb valid and reliable

<p>Abstract</p> <p>Background</p> <p>Visual estimation (VE) is an essential tool for evaluation of range of motion. Few papers discussed its validity in children orthopedics' practice. The purpose of our study was to assess validity and reliability of VE for passive range of motions (PROMs) of children's lower limbs.</p> <p>Methods</p> <p>Fifty typically developing children (100 lower limbs) were examined. Visual estimations for PROMs of hip (flexion, adduction, abduction, internal and external rotations), knee (flexion and popliteal angle) and ankle (dorsiflexion and plantarflexion) were made by a pediatric orthopaedic surgeon (POS) and a 5^thyear resident in orthopaedics. A last year medical student did goniometric measurements. Three weeks later, same measurements were performed to assess reliability of visual estimation for each examiner.</p> <p>Results</p> <p>Visual estimations of the POS were highly reliable for hip flexion, hip rotations and popliteal angle (ρ_c≥ 0.8). Reliability was good for hip abduction, knee flexion, ankle dorsiflexion and plantarflexion (ρ_c≥ 0.7) but poor for hip adduction (ρ_c= 0.5). Reproducibility for all PROMs was verified. Resident's VE showed high reliability (ρ_c≥ 0.8) for hip flexion and popliteal angle. Good correlation was found for hip rotations and knee flexion (ρ_c≥ 0.7). Poor results were obtained for ankle PROMs (ρ_c< 0.6) as well as hip adduction and abduction, the results of which not being reproducible. Influence of experience was clearly demonstrated for PROMs of hip rotations, adduction and abduction as well as ankle plantarflexion.</p> <p>Conclusion</p> <p>Accuracy of VE of passive hip flexion and knee PROMs is high regardless of the examiner's experience. Same accuracy can be found for hip rotations and abduction whenever VE is performed by an experienced examiner. Goniometric evaluation is recommended for passive hip adduction and for ankle PROMs.</p

Longest sediment flows yet measured show how major rivers connect efficiently to deep sea

Here we show how major rivers can efficiently connect to the deep-sea, by analysing the longest runout sediment flows (of any type) yet measured in action on Earth. These seafloor turbidity currents originated from the Congo River-mouth, with one flow travelling >1,130 km whilst accelerating from 5.2 to 8.0 m/s. In one year, these turbidity currents eroded 1,338-2,675 [>535-1,070] Mt of sediment from one submarine canyon, equivalent to 19–37 [>7–15] % of annual suspended sediment flux from present-day rivers. It was known earthquakes trigger canyon-flushing flows. We show river-floods also generate canyon-flushing flows, primed by rapid sediment-accumulation at the river-mouth, and sometimes triggered by spring tides weeks to months post-flood. It is demonstrated that strongly erosional turbidity currents self-accelerate, thereby travelling much further, validating a long-proposed theory. These observations explain highly-efficient organic carbon transfer, and have important implications for hazards to seabed cables, or deep-sea impacts of terrestrial climate change

Relationship between childhood physical abuse and clinical severity of treatment-resistant depression in a geriatric population

Introduction: We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample. Methods: Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres. Results: Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0–60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0–27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0–30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly’s Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect. Conclusion: To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

ESTUDO DE CASO: AVALIAÇÃO DA QUALIDADE DA ÁGUA DO LAGO DA PEDRA BRANCA, PALHOÇA, SC

Located 15 kilometers from the center of Florianópolis, the municipality of Palhoça has the white stone neighborhood, which stands out from other neighborhoods because it was planned in the late 90s and designed with sustainability and balance between urban occupation, quality of life and respect to the environment. It started with the transformation of a family farm and currently attracts people from diferente regions by presenting options for socializing and leisure for all ages who come to enjoy the parks, squares, lakes and open-air rest áreas. In May 2019, the neighborhood association detected the death of ducks that liver around the lake and trhough analysis by a veterinarian, the presence of the bactéria responsible for Botulism in the lake water was detected. The students of the Master in Environmental Sciences at UNISUL, accompanied by the teachers, went to the site and collected water samples to analyze in the laboratory. Measurements of pH, turbity, Dissolved Oxygen, BOD, Phosphorus, Ammoniacal Nitrogen, Nitrite, Nitrate and Thermotolerant Coliforms were made in two water samples collected on May 27 and June 10, 2019. The samples were collected following the Collection and Preservation of CETESB Samples and analyzed following themethodology described by the Standard Methods of Examination of Water and Wastewater. The pH, turbity, dissolved oxygen, nitrite and nitrate values were within the range recommended by CONAMA Resolution 357/2005. As for the parameters BOD, Phosphorus, Ammoniacal Nitrogen and Thermotolerant Coliforms, the values determined were well above the ideal range for Waters whose use is dedicated to primary contact recration, suggesting possible contamination by domestic effluents. In order to offer the Community a way oftreating and preventing the emergence of new diseases, resulting in the death of animals residente there, as well as preventing the lake from being used as a leisure source, forced aeration tests were performed on the collected water samples, and the results obtained were consistente with class 1 fresh water, suitable for primary contact recreation.Localizado a 15 quilômetros do centro de Florianópolis, o município de Palhoça, o bairro Pedra Branca, se destaca dos demais bairros por ter sido planejado no final da década de 90, buscando o equilíbrio entre a ocupação urbana, qualidade de vida e respeito ao meio ambiente. Iniciou pela transformação de uma fazenda familiar, e atualmente atrai pessoas de diversas regiões por apresentar opções de convivência e lazer para as pessoas de todas as idades que podem desfrutar dos parques, praças, lagos e áreas de descanso a céu aberto. Em maio de 2019, a associação de moradores do bairro, detectou a mortandade de patos que viviam no entorno do lago Pedra Branca e através de análises, foi detectada a presença na água da bactéria responsável pela mortandade dos patos, Clostridium spp (botulismo). Amostras de água foram coletadas no Lago Pedra Branca e realizadas análise de pH, turbidez, oxigênio dissolvido (OD), demanda bioquímica de oxigênio (DBO), fósforo, nitrogênio amoniacal, nitrito, nitrato e coliformes termotolerantes. As amostras foram coletadas seguindo o guia de coleta e preservação de amostras da CETESB e analisadas de acordo com a metodologia descrita pelo Standard Methods of Examination of Water and Wastewater (ALPHA, 2012). Os valores de pH, turbidez, oxigênio dissolvido, nitrito e nitrato seapresentaram dentro da faixa recomendada pela Resolução CONAMA 357/2005. Entretanto, para os parâmetros DBO, fósforo, nitrogênio amoniacal e coliformes termotolerantes, os valores se apresentaram acima dos limites máximos permitidos, onde o uso se aplica a recreação de contato primário, sugerindo uma possível contaminação por matéria orgânica e/ou efluentes domésticos. Com objetivo de fornecer à comunidade uma forma de tratamento e prevenir o surgimento de novas doenças, acarretando na mortandade de novos animais ali residentes, bem como o impedimento de utilização do lago como fonte de lazer, foram realizados testes de aeração forçada nas amostras de água coletadas, e os resultados obtidos ficaram condizentes com uma água doce Classe 1, própria para recreação de contato primário

Turbidity currents can dictate organic carbon fluxes across river-fed fjords: an example from Bute Inlet (BC, Canada)

The delivery and burial of terrestrial particulate organic carbon (OC) in marine sediments is important to quantify, because this OC is a food resource for benthic communities, and if buried it may lower the concentrations of atmospheric CO2 over geologic timescales. Analysis of sediment cores has previously shown that fjords are hotspots for OC burial. Fjords can contain complex networks of submarine channels formed by seafloor sediment flows, called turbidity currents. However, the burial efficiency and distribution of OC by turbidity currents in river-fed fjords had not been investigated previously. Here, we determine OC distribution and burial efficiency across a turbidity current system within Bute Inlet, a fjord in western Canada. We show that 62% ± 10% of the OC supplied by the two river sources is buried across the fjord surficial (30–200 cm) sediment. The sandy subenvironments (channel and lobe) contain 63% ± 14% of the annual terrestrial OC burial in the fjord. In contrast, the muddy subenvironments (overbank and distal basin) contain the remaining 37% ± 14%. OC in the channel, lobe, and overbank exclusively comprises terrestrial OC sourced from rivers. When normalized by the fjord’s surface area, at least 3 times more terrestrial OC is buried in Bute Inlet, compared to the muddy parts of other fjords previously studied. Although the long-term (>100 years) preservation of this OC is still to be fully understood, turbidity currents in fjords appear to be efficient at storing OC supplied by rivers in their near-surface deposits