Return to the workforce following first hospitalization for heart failure: a Danish nationwide cohort study

Background: Return to work is important financially, as a marker of functional status and for self-esteem in patients developing chronic illness. We examined return to work after first heart failure (HF) hospitalization. Methods: By individual-level linkage of nationwide Danish registries, we identified 21455 patients of working age (18-60 years) with a first HF hospitalization in the period of 1997-2012. Of these 11880 (55%) were in the workforce prior to HF hospitalization and comprised the study population. We applied logistic regression to estimate odds ratios (OR) for associations between age, sex, length of hospital stay, level of education, income, comorbidity and return to work. Results: One year after first HF hospitalization, 8040 (67.7%) returned to the workforce, 2981 (25.1%) did not, 805 (6.7%) died and 54 (0.5%) emigrated. Predictors of return to work included younger age (18-30 vs. 51-60 years, OR 3.12; 95% CI 2.42-4.03), male sex (OR 1.22 [1.18-1.34]) and level of education (long-higher vs. basic school OR 2.06 [1.63-2.60]). Conversely, hospital stay >7 days (OR 0.56 [0.51-0.62]) and comorbidity including history of stroke (OR 0.55 [0.45-0.69]), chronic kidney disease (OR 0.46 [0.36-0.59]), chronic obstructive pulmonary disease (OR 0.62 [0.52-0.75]), diabetes (OR 0.76 [0.68-0.85]) and cancer (OR 0.49 [0.40-0.61]) were all significantly associated with lower chance of return to work. Conclusions: Patients in the workforce prior to HF hospitalization had low mortality but high risk of detachment from the workforce one year later. Young age, male sex, and higher level of education were predictors of return to work

Privacy Risks of Securing Machine Learning Models against Adversarial Examples

The arms race between attacks and defenses for machine learning models has come to a forefront in recent years, in both the security community and the privacy community. However, one big limitation of previous research is that the security domain and the privacy domain have typically been considered separately. It is thus unclear whether the defense methods in one domain will have any unexpected impact on the other domain. In this paper, we take a step towards resolving this limitation by combining the two domains. In particular, we measure the success of membership inference attacks against six state-of-the-art defense methods that mitigate the risk of adversarial examples (i.e., evasion attacks). Membership inference attacks determine whether or not an individual data record has been part of a model's training set. The accuracy of such attacks reflects the information leakage of training algorithms about individual members of the training set. Adversarial defense methods against adversarial examples influence the model's decision boundaries such that model predictions remain unchanged for a small area around each input. However, this objective is optimized on training data. Thus, individual data records in the training set have a significant influence on robust models. This makes the models more vulnerable to inference attacks. To perform the membership inference attacks, we leverage the existing inference methods that exploit model predictions. We also propose two new inference methods that exploit structural properties of robust models on adversarially perturbed data. Our experimental evaluation demonstrates that compared with the natural training (undefended) approach, adversarial defense methods can indeed increase the target model's risk against membership inference attacks.Comment: ACM CCS 2019, code is available at https://github.com/inspire-group/privacy-vs-robustnes

Heart failure in young adults is associated with high mortality: a contemporary population-level analysis

Background: Data on young patients with heart failure (HF) are sparse. We examined the characteristics, healthcare utilization and survival of younger versus older patients with HF. Methods: Analysis of linked administrative databases in Alberta, Canada. 34,548 patients with first hospitalization for HF as principal diagnosis were identified from 2002 to 2014. Patients were stratified into four age groups: 20-44, 45-54, 55-64, and ≥65 years. Results: Of the 34548 patients, 496 (1.4%), 1319 (3.8%), 3359 (9.7%) and 29374 (85%) patients were aged 20-44, 45-54, 55-64 and ≥65 years, respectively. Incidence of HF hospitalization decreased over time among patients ≥65 years, and increased among men aged 20 – 64 years. In the year following the index HF hospitalization, younger compared to older patients were less likely to present to the emergency department (ED) (e.g. 67.2% of those aged 20-44 years vs. 74.8% of those aged ≥65 years) or be hospitalized: for any reason (48.5% vs. 61.2%), cardiovascular causes (28.6% vs. 34.4%), or HF (14.8% vs. 23.6%). Mortality rates were lower in younger patients aged 20-44 years, but still substantial: 3.9%, 12.4%, and 27.7% at 30 days, 1 year, and 5 years respectively. Conclusions: Although young patients, especially those <45 years of age, accounted for a small proportion of the total population, adverse events were frequent, with half of the younger patients being readmitted, two thirds presenting to an ED, and over 10% dying within a year

Development of a thermostable, multivalent filovirus vaccine based on recombinant subunit proteins

Ebola Virus Disease (EVD) is the most prominent example of filovirus disease but despite being characterized as a Category A Priority Pathogen by NIH/NIAID over a decade ago, it lacked public and private research resources due to the absence of a commercial market. Transmission from wild animals into the human population typically causes outbreaks of limited scale in endemic areas located in the forested regions of Central Africa and the Philippines (for Reston ebolavirus). In the past decade, a Zaire Ebolavirus (EBOV) outbreak causing more than 11,000 deaths in several West African countries started to reveal the true epidemic potential that filovirus infections can have when entering an urban setting in a highly mobile society. In addition a persistent outbreak in the Democratic Republic of the Congo has continued since August 2018 despite significant progress with the clinical development of several EBOV vaccine candidates (one of which recently gained regulatory approvals in Europe, the U.S. and several African countries) and the advanced testing of promising EBOV specific therapeutics. Despite this significant progress, additional research is needed in particular on understanding the mechanism of protection and defining immune correlates of protection for Ebola and other filoviruses do develop fast and efficacious strategies for outbreak control as the incidence of outbreaks and total case numbers has significantly increased over the last decadesPlease click Download on the upper right corner to see the full abstract

RONIN Is an Essential Transcriptional Regulator of Genes Required for Mitochondrial Function in the Developing Retina

SummaryA fundamental principle governing organ size and function is the fine balance between cell proliferation and cell differentiation. Here, we identify RONIN (THAP11) as a key transcriptional regulator of retinal progenitor cell (RPC) proliferation. RPC-specific loss of Ronin results in a phenotype strikingly similar to that resulting from the G1- to S-phase arrest and photoreceptor degeneration observed in the Cyclin D1 null mutants. However, we determined that, rather than regulating canonical cell-cycle genes, RONIN regulates a cohort of mitochondrial genes including components of the electron transport chain (ETC), which have been recently implicated as direct regulators of the cell cycle. Coincidentally, with premature cell-cycle exit, Ronin mutants exhibited deficient ETC activity, reduced ATP levels, and increased oxidative stress that we ascribe to specific loss of subunits within complexes I, III, and IV. These data implicate RONIN as a positive regulator of mitochondrial gene expression that coordinates mitochondrial activity and cell-cycle progression

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

Breast cancer derived GM-CSF regulates arginase 1 in myeloid cells to promote an immunosuppressive microenvironment

Tumor-infiltrating myeloid cells contribute to the development of the immunosuppressive tumor microenvironment. Myeloid cell expression of arginase 1 (Arg-1) promotes a protumor phenotype by inhibiting T cell function and depleting extracellular L-arginine, but the mechanism underlying this expression, especially in breast cancer, is poorly understood. In breast cancer clinical samples and in our mouse models, we identified tumor derived GM-CSF as the primary regulator of myeloid cell Arg-1 expression and local immune suppression through a gene knockout screen of breast tumor cell-produced factors. The induction of myeloid cell Arg-1 required GM-CSF and a low pH environment. GM-CSF signaling through STAT3, p38 MAPK, and acid signaling through cAMP were required to activate myeloid cell Arg-1 expression in a STAT6 independent manner. Importantly, breast tumor cell-derived GM-CSF promoted tumor progression by inhibiting host anti-tumor immunity, driving a significant accumulation of Arg-1 expressing myeloid cells compared to lung and melanoma tumors with minimal GM-CSF expression. Blockade of tumoral GM-CSF enhanced the efficacy of tumor-specific adoptive T-cell therapy and immune checkpoint blockade. Taken together, breast tumor cell-derived GM-CSF contributes to the development of the immunosuppressive breast cancer microenvironment by regulating myeloid cell Arg-1 expression and can be targeted to enhance breast cancer immunotherapy

Automatic segmentation of meningioma from non-contrasted brain MRI integrating fuzzy clustering and region growing

<p>Abstract</p> <p>Background</p> <p>In recent years, magnetic resonance imaging (MRI) has become important in brain tumor diagnosis. Using this modality, physicians can locate specific pathologies by analyzing differences in tissue character presented in different types of MR images.</p> <p>This paper uses an algorithm integrating fuzzy-c-mean (FCM) and region growing techniques for automated tumor image segmentation from patients with menigioma. Only non-contrasted T1 and T2 -weighted MR images are included in the analysis. The study's aims are to correctly locate tumors in the images, and to detect those situated in the midline position of the brain.</p> <p>Methods</p> <p>The study used non-contrasted T1- and T2-weighted MR images from 29 patients with menigioma. After FCM clustering, 32 groups of images from each patient group were put through the region-growing procedure for pixels aggregation. Later, using knowledge-based information, the system selected tumor-containing images from these groups and merged them into one tumor image. An alternative semi-supervised method was added at this stage for comparison with the automatic method. Finally, the tumor image was optimized by a morphology operator. Results from automatic segmentation were compared to the "ground truth" (GT) on a pixel level. Overall data were then evaluated using a quantified system.</p> <p>Results</p> <p>The quantified parameters, including the "percent match" (PM) and "correlation ratio" (CR), suggested a high match between GT and the present study's system, as well as a fair level of correspondence. The results were compatible with those from other related studies. The system successfully detected all of the tumors situated at the midline of brain.</p> <p>Six cases failed in the automatic group. One also failed in the semi-supervised alternative. The remaining five cases presented noticeable edema inside the brain. In the 23 successful cases, the PM and CR values in the two groups were highly related.</p> <p>Conclusions</p> <p>Results indicated that, even when using only two sets of non-contrasted MR images, the system is a reliable and efficient method of brain-tumor detection. With further development the system demonstrates high potential for practical clinical use.</p

Age- and gender-specific population attributable risks of metabolic disorders on all-cause and cardiovascular mortality in Taiwan

[[abstract]]ABSTRACT: BACKGROUND: The extent of attributable risks of metabolic syndrome (MetS) and its components on mortality remains unclear, especially with respect to age and gender. We aimed to assess the age- and gender-specific population attributable risks (PARs) for cardiovascular disease (CVD)-related mortality and all-cause mortality for public health planning. METHODS: A total of 2,092 men and 2,197 women 30 years of age and older, who were included in the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), were linked to national death certificates acquired through December 31, 2009. Cox proportional hazard models were used to calculate adjusted hazard ratios and PARs for mortality, with a median follow-up of 7.7 years. RESULTS: The respective PAR percentages of MetS for all-cause and CVD-related mortality were 11.6 and 39.2 in men, respectively, and 18.6 and 44.4 in women, respectively. Central obesity had the highest PAR for CVD mortality in women (57.5%), whereas arterial hypertension had the highest PAR in men (57.5%). For all-cause mortality, younger men and post-menopausal women had higher PARs related to Mets and its components; for CVD mortality, post-menopausal women had higher overall PARs than their pre-menopausal counterparts. CONCLUSIONS: MetS has a limited application to the PAR for all-cause mortality, especially in men; its PAR for CVD mortality is more evident. For CVD mortality, MetS components have higher PARs than MetS itself, especially hypertension in men and waist circumference in post-menopausal women. In addition, PARs for diabetes mellitus and low HDL-cholesterol may exceed 20%. We suggest differential control of risk factors in different subpopulation as a strategy to prevent CVD-related mortality

The clathrin heavy chain isoform CHC22 functions in a novel endosomal sorting step

CHC22 is needed for retrograde trafficking from endosomes to the trans-Golgi, unlike its clathrin sibling CHC17, and in a manner distinct from retromer