Cohort-based kernel principal component analysis with Multi-path Service Routing in Federated Learning

Federated Learning (FL) is a machine learning (ML) strategy that is performed in a decentralized environment. The training is performed locally by the client on the global model shared by the server. Federated learning has recently been used as a service (FLaaS) to provide a collaborative training environment to independent third-party applications. However, the widespread adoption in distributed settings of FL has opened venues for a number of security attacks. A number of studies have been performed to prevent multiple FL attacks. However, sophisticated attacks, such as label-flipping attacks, have received little or no attention. From the said perspective, this research is focused on providing a defense mechanism for the aforesaid attack. The proposed approach is based on Type-based Cohorts (TC) with Kernel Principal Component Analysis (KPCA) to detect and defend against label-flipping attacks. Moreover, to improve the performance of the network, we will deploy Multi-path Service Routing (MSR) for edge nodes to work effectively. The KPCA will be used to secure the network from attacks. The proposed mechanism will provide an effective and secure FL system. The proposed approach is evaluated with respect to the following measures: execution time, memory consumption, information loss, accuracy, service request violations, and the request’s waiting time

Influence of β-galacto-oligosaccharide on growth performance and components of intestinal barrier in broilers during heat stress

This study aimed to investigate the influence of β-galacto-oligosaccharides (β-GOS) on growth performance, organ development and intestinal microarchitecture of broilers during heat stress. Day-old chicks (n = 125) were divided into five groups. The control or thermoneutral zone group (TNZ) was raised under standard management until the 35th day. Four groups were exposed to cyclic heat stress (35 °C 8 h/d) from the 22nd to the 35th day. The TNZ and heat stress control (HSCT) groups were fed a corn-based diet and HS + 0.1% β-GOS; HS + 0.2% β-GOS; and HS + 0.5% β-GOS were fed a corn-based diet supplemented with β-GOS (0.1%, 0.2%, and 0.5%), respectively. Exposure to heat stress reduced feed consumption, feed efficiency and the relative weight of the liver, bursa of Fabricius, and small intestine, compared with the TNZ group. Morphometric evaluation of the small intestine revealed reduced villus surface area, villus height to crypt depth ratio (VH : CD) and intraepithelial lymphocytes (IELs) in all segments, and reduced acidic goblet cells (AGCs) in the ileum of the HSCT group compared with the TNZ group. Compared with the HSCT group, dietary β-GOS (0.2% and 0.5%) improved the feed efficiency and relative weight of the small intestine. Furthermore, dietary β-GOS (0.1%) increased villus surface area in the duodenum and IEL count in the small intestine compared with the HSCT group. Dietary β-GOS 0.5% increased villi surface area (VSA) in the jejunum and ileum, whereas the IEL count in the small intestine and acidic goblet cells (AGCs) in the jejunum and ileum were reduced compared with the HSCT group. In conclusion, dietary supplementation of β-GOS (0.2% and 0.5%) improved the growth performance and intestinal microarchitecture of broilers during heat exposure, along with partial immune stimulation. Keywords: Feed efficiency, goblet cell, intraepithelial lymphocytes, mucosal architecture, prebiotics, poultry, villus morphometr

Students' Feedback of Written Examination: A Public Sector Medical University Experience

Objective: To determine the students’ perceptions regarding the examination in a public sector medical university. Methodology: This cross-sectional study was conducted at Shaheed Zulfiqar Ali Bhutto Medical University Islamabad. An examination feedback proforma was developed to collect the feedback from students appearing for the written exam for MD/MS/MTA during 2015. Multiple variables were assessed and descriptive analysis was done. Results: The feedback proforma was distributed to 98 candidates with response rate was 68.36%. Overall feedback from students about the examination was positive. Majority of the students were satisfied with the process and arrangements of the examination. However a large number of students did not comment on some important issues. Conclusion: Collecting students’ feedback about examination was a good effort to identify our deficiencies and indication for areas of improvement. This study revealed a positive response from students regarding overall management of the examination process

Pregabalin Suppresses Spinal Neuronal Hyperexcitability and Visceral Hypersensitivity in the Absence of Peripheral Pathophysiology

ABSTRACT Background: Opioid-induced hyperalgesia is recognized in the laboratory and the clinic, generating central hyperexcitability in the absence of peripheral pathology. We investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that disrupts descending serotonergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid-induced hyperalgesia. Methods: Male Sprague-Dawley rats (180 -200 g) were implanted with osmotic mini-pumps filled with morphine (90 g ⅐ l Ϫ1 ⅐

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care

Time trends of delirium rates in the intensive care unit

Background: Effects of clinical practice changes on ICU delirium are not well understood. Objectives: Determine ICU delirium rates over time. Methods: Data from a previously described screening cohort of the Pharmacological Management of Delirium trial was analyzed. Richmond Agitation-Sedation Scale (RASS) and Confusion Assessment Method for the ICU (CAM-ICU) were assessed twice daily. We defined: Any delirium (positive CAM-ICU at any time during ICU stay) and ICU-acquired delirium (1st CAM-ICU negative with a subsequent positive CAM-ICU). Mixed-effects logistic regression models were used to test for differences. Results: 2742 patient admissions were included. Delirium occurred in 16.5%, any delirium decreased [22.7% to 10.2% (p < 0.01)], and ICU-acquired delirium decreased [8.4% to 4.4% (p = 0.01)]. Coma decreased from 24% to 17.4% (p = 0.04). Later ICU years and higher mean RASS scores were associated with lower odds of delirium. Conclusions: Delirium rates were not explained by the measured variables and further prospective research is needed

A novel human pain insensitivity disorder caused by a point mutation in ZFHX2

Chronic pain is a major global public health issue causing a severe impact on both the quality of life for sufferers and the wider economy. Despite the significant clinical burden, little progress has been made in terms of therapeutic development. A unique approach to identifying new human-validated analgesic drug targets is to study rare families with inherited pain insensitivity. Here we have analysed an otherwise normal family where six affected individuals display a pain insensitive phenotype that is characterized by hyposensitivity to noxious heat and painless bone fractures. This autosomal dominant disorder is found in three generations and is not associated with a peripheral neuropathy. A novel point mutation in ZFHX2, encoding a putative transcription factor expressed in small diameter sensory neurons, was identified by whole exome sequencing that segregates with the pain insensitivity. The mutation is predicted to change an evolutionarily highly conserved arginine residue 1913 to a lysine within a homeodomain. Bacterial artificial chromosome (BAC) transgenic mice bearing the orthologous murine p.R1907K mutation, as well as Zfhx2 null mutant mice, have significant deficits in pain sensitivity. Gene expression analyses in dorsal root ganglia from mutant and wild-Type mice show altered expression of genes implicated in peripheral pain mechanisms. The ZFHX2 variant and downstream regulated genes associated with a human pain-insensitive phenotype are therefore potential novel targets for the development of new analgesic drugs. awx326media1 5680039660001 The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.We thank the Medical Research Council (J.J.C., Career Development Award, G1100340), Wellcome Trust (200183/ Z/15/Z and 101054/Z/13/Z) and Arthritis Research UK (20200) for generous support and Shionogi for an academic research grant (165302). Thanks to the University of Siena for partially funding this research. J.T.B. is supported by a Research Fellowship from the Alzheimer�s Society. J.D.R. received funding from the Wellcome Trust through the London Pain Consortium and from Colciencias through a Francisco Jose de Caldas Scholarship (LASPAU, Harvard University). D.L.H.B. is a Wellcome senior clinical scientist (ref. no. 095698z/11/z and 202747/Z/16/Z) and member of the Wellcome Pain Consortium.Scopu

γ-Secretase inhibitor enhances antitumour effect of radiation in Notch-expressing lung cancer

BACKGROUND: Notch receptor has an important role in both development and cancer. We previously reported that inhibition of the Notch3 by γ-secretase inhibitor (GSI) induces apoptosis and suppresses tumour proliferation in non-small-cell lung cancer. Although radiation is reported to induce Notch activation, little is known about the relationship between radiation and Notch pathway. METHODS: We examined the effect of combining GSI and radiation at different dosing in three Notch expressing lung cancer cell lines. The cytotoxic effect of GSI and radiation was evaluated using MTT assay and clonogenic assay in vitro and xenograft models. Expressions of Notch pathway, mitogen-activated protein kinase (MAPK) pathway and Bcl-2 family proteins were investigated using western blot analysis. RESULTS: We discovered that the antitumour effect of combining GSI and radiation was dependent on treatment schedule. γ-Secretase inhibitor administration after radiation had the greatest growth inhibition of lung cancer in vitro and in vivo. We showed that the combination induced apoptosis of lung cancer cell lines through the regulation of MAPK and Bcl-2 family proteins. Furthermore, activation of Notch after radiation was ameliorated by GSI administration, suggesting that treatment with GSI prevents Notch-induced radiation resistance. CONCLUSION: Notch has an important role in lung cancer. Treatment with GSI after radiation can significantly enhance radiation-mediated tumour cytotoxicity

A novel human pain insensitivity disorder caused by a point mutation in ZFHX2

Chronic pain is a major global public health issue causing a severe impact on both the quality of life for sufferers and the wider economy. Despite the significant clinical burden, little progress has been made in terms of therapeutic development. A uniquepowerful approach to identifying new human-validated analgesic drug targets is to study rare families with inherited pain insensitivity. Here we have analysed an otherwise normal family where six affected individuals display a pain insensitive phenotype that is characterized by hyposensitivity to noxious heat and painless bone fractures. This autosomal dominant disorder is found in three generations and is not associated with a peripheral neuropathy. A novel point mutation in ZFHX2, encoding a putative transcription factor expressed in small diameter sensory neurons, was identified by whole exome sequencing that segregates with the pain insensitivity. The mutation is predicted to change an evolutionarily highly conserved arginine residue 1913 to a lysine within a homeodomain. BAC transgenic mice bearing the orthologous murine p.R1907K mutation, as well as Zfhx2 null mutant mice, have significant deficits in pain sensitivity. Gene expression analyses in dorsal root ganglia from mutant and wild-type mice show altered expression of genes implicated in peripheral pain mechanisms. The ZFHX2 variant and downstream regulated genes associated with a human paininsensitive phenotype are therefore potential novel targets for the development of new analgesic drugs