Pancreas Cancer-Associated Weight Loss.

Unintentional weight loss in patients with pancreatic cancer is highly prevalent and contributes to low therapeutic tolerance, reduced quality of life, and overall mortality. Weight loss in pancreatic cancer can be due to anorexia, malabsorption, and/or cachexia. Proper supportive care can stabilize or reverse weight loss in patients and improve outcomes. We review the literature on supportive care relevant to pancreatic cancer patients, and offer evidence-based recommendations that include expert nutritional assessment, counseling, supportive measures to ensure adequate caloric intake, pancreatic enzyme supplementation, nutritional supplement replacement, orexigenic agents, and exercise. Pancreatic Cancer Action Network-supported initiatives will spearhead the dissemination and adoption of these best supportive care practices. IMPLICATIONS FOR PRACTICE: Weight loss in pancreatic cancer patients is endemic, as 85% of pancreatic cancer patients meet the classic definition of cancer cachexia. Despite its significant prevalence and associated morbidity, there is no established approach to this disease entity. It is believed that this is due to an important knowledge gap in understanding the underlying biology and lack of optimal treatment approaches. This article reviews the literature regarding pancreas cancer-associated weight loss and establishes a new framework from which to view this complex clinical problem. An improved approach and understanding will help educate clinicians, improve clinical care, and provide more clarity for future clinical investigation

Graduate employability skills

This report examines how universities currently develop and teach undergraduate students employability skills, and how graduate employability skills might be assessed and reported on in the future. The report presents recommendations based on an integrated approach that emphasises improved processes for identifying, developing, assessing and reporting on graduate employability skills. Examples and descriptions of similar work already being carried out across the higher education sector are provided in the main body of the report

Prostate Imaging Quality (PI-QUAL): A New Quality Control Scoring System for Multiparametric Magnetic Resonance Imaging of the Prostate from the PRECISION trial

The PRECISION trial was a multicentre randomised study that demonstrated that multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy is superior to standard transrectal ultrasound-guided biopsy for the detection of prostate cancer. The outcomes of studies reporting mpMRI-targeted biopsies are dependent on the quality of the mpMRI but there are currently no scoring systems available for evaluating this. We introduced a novel scoring system, the Prostate Imaging Quality (PI-QUAL) score, to assess the quality of scans in the PRECISION trial. PI-QUAL is a score on a Likert scale from 1 to 5, where 1 means that no mpMRI sequences are of diagnostic quality and 5 implies that each sequence is independently of optimal diagnostic quality. Fifty-eight out of 252 (23%) mpMRI scans chosen at random from each of the 22 centres in this trial were evaluated by two experienced radiologists from the coordinating trial centre, in consensus, blinded to pathology results. Overall, the mpMRI quality in the centres participating in PRECISION was good. MpMRI quality was of sufficient diagnostic quality (PI-QUAL ≥3) for 55 scans (95%) and of good or optimal diagnostic quality (PI-QUAL ≥4) for 35 scans (60%). Fifty-five out of 58 (95%) scans were of diagnostic quality for T2WI, followed by DWI (46/58 scans; 79%), and DCE (38/58 scans; 66%). Further validation of this scoring system is warranted. PATIENT SUMMARY: In this study we developed a scoring system (PI-QUAL) to assess the quality of multiparametric magnetic resonance imaging (mpMRI) in prostate cancer detection. We used scans from 22 centres that participated in the PRECISION trial. Although there was room for improvement in images that used intravenous contrast, we found that mpMRI in the PRECISION trial was of sufficient diagnostic quality (PI-QUAL score ≥3) for 95% of the scans

Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study.

BACKGROUND:Current methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimer's disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic estimates and can be used to stage an individual's amyloid burden in vivo. Here, we evaluated the validity of this in vivo amyloid staging model in an independent cohort of older people with subjective memory complaints (SMC). We further examined its potential association with subtle cognitive impairments in this population at elevated risk for Alzheimer's disease (AD). METHODS:The monocentric INSIGHT-preAD cohort includes 318 cognitively intact older individuals with SMC. All individuals underwent 18F-florbetapir PET scanning and extensive neuropsychological testing. We projected the regional amyloid uptake signal into the previously proposed hierarchical staging model of in vivo amyloid progression. We determined the adherence to this model across all cases and tested the association between increasing in vivo amyloid stage and cognitive performance using ANCOVA models. RESULTS:In total, 156 participants (49%) showed evidence of regional amyloid deposition, and all but 2 of these (99%) adhered to the hierarchical regional pattern implied by the in vivo amyloid progression model. According to a conventional binary classification based on global signal (SUVRCereb = 1.10), individuals in stages III and IV were classified as amyloid-positive (except one in stage III), but 99% of individuals in stage I and even 28% of individuals in stage II were classified as amyloid-negative. Neither in vivo amyloid stage nor conventional binary amyloid status was significantly associated with cognitive performance in this preclinical cohort. CONCLUSIONS:The proposed hierarchical staging scheme of PET-evidenced amyloid deposition generalizes well to data from an independent cohort of older people at elevated risk for AD. Future studies will determine the prognostic value of the staging approach for predicting longitudinal cognitive decline in older individuals at increased risk for AD

Urinary Proteomics Identifies Cathepsin D as a Biomarker of Rapid eGFR Decline in Type 1 Diabetes

Publisher Copyright: © 2022 by the American Diabetes Association.OBJECTIVE Understanding mechanisms underlying rapid estimated glomerular filtration rate (eGFR) decline is important to predict and treat kidney disease in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS We performed a case-control study nested within four T1D cohorts to identify urinary proteins associated with rapid eGFR decline. Case and control subjects were categorized based on eGFR decline ≥3 and <1 mL/min/1.73 m2 /year, respectively. We used targeted liquid chromatography–tandem mass spectrome-try to measure 38 peptides from 20 proteins implicated in diabetic kidney dis-ease. Significant proteins were investigated in complementary human cohorts and in mouse proximal tubular epithelial cell cultures. RESULTS The cohort study included 1,270 participants followed a median 8 years. In the discovery set, only cathepsin D peptide and protein were significant on full adjustment for clinical and laboratory variables. In the validation set, associations of cathepsin D with eGFR decline were replicated in minimally adjusted models but lost significance with adjustment for albuminuria. In a meta-analysis with combination of discovery and validation sets, the odds ratio for the association of cathepsin D with rapid eGFR decline was 1.29 per SD (95% CI 1.07–1.55). In complementary human cohorts, urine cathepsin D was associated with tubulointerstitial injury and tubulointerstitial cathepsin D expression was associated with increased cortical interstitial fractional volume. In mouse proximal tubular epithelial cell cultures, advanced glycation end product–BSA increased cathepsin D activity and inflammatory and tubular injury markers, which were further increased with cathepsin D siRNA. CONCLUSIONS Urine cathepsin D is associated with rapid eGFR decline in T1D and reflects kidney tubulointerstitial injury.Peer reviewe

Genetic Algorithm for the Weight Maximization Problem on Weighted Automata

The weight maximization problem (WMP) is the problem of finding the word of highest weight on a weighted finite state automaton (WFA). It is an essential question that emerges in many optimization problems in automata theory. Unfortunately, the general problem can be shown to be undecidable, whereas its bounded decisional version is NP-complete. Designing efficient algorithms that produce approximate solutions to the WMP in reasonable time is an appealing research direction that can lead to several new applications including formal verification of systems abstracted as WFAs. In particular, in combination with a recent procedure that translates a recurrent neural network into a weighted automaton, an algorithm for the WMP can be used to analyze and verify the network by exploiting the simpler and more compact automata model. In this work, we propose, implement and evaluate a metaheuristic based on genetic algorithms to approximate solutions to the WMP. We experimentally evaluate its performance on examples from the literature and show its potential on different applications.Comment: Accepted at GECCO 202

Menopause hormone therapy significantly alters pathophysiological biomarkers of Alzheimer's disease

INTRODUCTION: This increasing body of literature indicates that menopause hormonal replacement therapy (MHT) may substantially mitigate the risk of developing late-life cognitive decline due to progressive Alzheimer's disease (AD) pathophysiology. For the first time, we investigated the question whether MHT impacts AD biomarker-informed pathophysiological dynamics in de-novo diagnosed menopausal women. METHODS: We analyzed baseline and longitudinal differences between MHT-taking and -not women in terms of concentrations of core pathophysiological AD plasma biomarkers, validated in symptomatic and cognitively healthy individuals, including biomarkers of (1) the amyloid-β (Aβ) pathway, (2) tau pathophysiology, (3) neuronal loss, and (4) axonal damage and neurodegeneration. RESULTS: We report a prominent and significant treatment response at the Aβ pathway biomarker level. Women at genetic risk for AD (APOE e4 allele carriers) have particularly shown favorable results from treatment. DISCUSSION: To our knowledge, we present first prospective clinical evidence on effects of MHT on AD pathophysiology during menopause

Higgs production in association with top quark pair at e+e- colliders in theories of higher dimensional gravity

The models of large extra compact dimensions, as suggested by Arkani-Hamed, Dimopoulos and Dvali, predict exciting phenomenological consequences with gravitational interactions becoming strong at the TeV scale. Such theories can be tested at the existing and future colliders. In this paper, we study the contribution of virtual Kaluza-Klein excitations in the process $e^+e^- \to t \bar t H$ at future linear collider (NLC). We find that the virtual exchange KK gravitons can modify the cross-section $\sigma(e^+e^- \to t \bar t H)$ significantly from its Standard Model value and will allow the effective string scale to be probed up to 7.9 TeV.Comment: 10 pages, Latex, 4 postscript figure

β-Secretase1 biological markers for Alzheimer's disease: state-of-art of validation and qualification

β-Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibitors to halt or delay the dysregulation of the amyloid-β pathway in Alzheimer’s disease (AD). A robust body of evidence demonstrates an association between cerebrospinal fluid/blood BACE1 biomarkers and core pathophysiological mechanisms of AD, such as brain protein misfolding and aggregration, neurodegeneration, and synaptic dysfunction. In pharmacological trials, BACE1 candidate biomarkers may be applied to a wide set of contexts of use (CoU), including proof of mechanism, dose-finding, response and toxicity dose estimation. For clinical CoU, BACE1 biomarkers show good performance for prognosis and disease prediction. The roadmap toward validation and qualification of BACE1 biomarkers requires standardized pre-analytical and analytical protocols to reduce inter-site variance that may have contributed to inconsistent results. BACE1 biomarker-drug co-development programs, including biomarker-guided outcomes and endpoints, may support the identification of sub-populations with a higher probability to benefit from BACE1 inhibitors with a reduced risk of adverse effects, in line with the evolving precision medicine paradigm

Recent Advances in Printed Capacitive Sensors

In this review paper, we summarize the latest advances in the field of capacitive sensors fabricated by printing techniques. We first explain the main technologies used in printed electronics, pointing out their features and uses, and discuss their advantages and drawbacks. Then, we review the main types of capacitive sensors manufactured with different materials and techniques from physical to chemical detection, detailing the main substrates and additives utilized, as well as the measured ranges. The paper concludes with a short notice on status and perspectives in the field.H2020-MSCA-IF-2017-794885-SELFSEN