Excess of Tau events at SND@LHC, FASERν\nu and FASERν\nu2

During the run III of the LHC, the forward experiments FASER$\nu$ and SND@LHC will be able to detect the Charged Current (CC) interactions of the high energy neutrinos of all three flavors produced at the ATLAS Interaction Point (IP). This opportunity may unravel mysteries of the third generation leptons. We build three models that can lead to a tau excess at these detectors through the following Lepton Flavor Violating (LFV) beyond Standard Model (SM) processes: (1) $\pi^+ \to \mu^+ \nu_\tau$; (2) $\pi^+ \to \mu^+ \bar{\nu}_\tau$ and (3) $\nu_e+{\rm nucleus}\to \tau +X$. We comment on the possibility of solving the $(g-2)_\mu$ anomaly and the $\tau$ decay anomalies within these models. We study the potential of the forward experiments to discover the $\tau$ excess or to constrain these models in case of no excess. We then compare the reach of the forward experiments with that of the previous as well as next generation experiments such as DUNE. We also discuss how the upgrade of FASER$\nu$ can distinguish between these models by studying the energy spectrum of the tau

Correlations of skin fold thickness and validation of prediction equations using DEXA as the gold standard for estimation of body fat composition in Pakistani children.

OBJECTIVE: To determine the correlation between dual energy X-ray absorptiometry (DEXA) and skin fold thickness (SKF) equations for estimation of body fat (BF) composition in secondary school children and validation of prediction equations by Slaughter, Goran and Dezenberg. DESIGN: Cross sectional analytical study. SETTING: Joint Commission for International Accredited (JCIA) tertiary care hospital of Karachi, Pakistan from January 2010 to May 2010. PARTICIPANTS: The study was approved by the Hospital\u27s ethical review committee. Written and verbal consents were obtained from principals of two schools and parents of 99 children (mean age of 14±1.89 years; min-max 9-19 years; 54 men and 45 women) accrued in study. DEXA scan was acquired and SKF was measured at angle of the scapula, iliac crest and mid-arm for bicep and tricep skin folds using Holtain Callipers. Correlations were established between estimated fat mass (FM) and per cent BF (%BF) calculated by DEXA and those predicted by prediction equations. On obtaining significant correlation of \u3e0.5, overall accuracy, precision and bias was calculated. RESULTS: There was an overall increased adiposity in females with FM of 3.57 kg and %BF 6.2% higher than male counterparts (p CONCLUSIONS: We conclude that Slaughter equation for estimating %BF showed reasonable validation with DEXA. Nevertheless further studies with consideration for maturity and ethnicity are warranted for better results. However, for estimation of FM, previously formulated equations by Goran and Dezenberg showed significant difference in our population. We do recommend further studies for developing and validation of skin fold equations specific to Pakistani paediatric populatio

Psychiatry as a career: A survey of factors affecting students’ interest in Psychiatry as a career

The objectives of this study were to determine the characteristics of medical students and graduates interested in choosing psychiatry as a career and the obstacles in choosing this field of medicine. Two private and two public medical institutes were surveyed from June 2007 to August 2007. A self-administered questionnaire was distributed to third, fourth and final year students and to medical graduates doing their internship in these four medical institutes. A total of 909 medical students and graduates participated in the study. Seventeen percent of participants responded positively regarding their interest in psychiatry as a career. Significantly higher proportion belonged to private medical institutes (14% vs. 24%, P-value =0.001). There was no significant difference in reporting interest for psychiatry in regard to age, sex, year in medical school and whether or not the participant had done a psychiatry ward rotation. However significantly higher proportion of participants (22%, n=43) were reporting their interest in the field of psychiatry who had done more than a month long psychiatry ward rotation as compared to those participants (14%, n=54) with less than a month or no psychiatry rotation (P-value=0.01). More students were reporting their interest in psychiatry with a family history of psychiatric illness as compared to without family history (24% vs 16%, P-value=0.03). In conclusion, students and graduates with more than a month long rotation in psychiatry, studying in private medical colleges and with a family history of psychiatric illness were more interested in choosing psychiatry as a career

Learning Nonlinear Loop Invariants with Gated Continuous Logic Networks (Extended Version)

Verifying real-world programs often requires inferring loop invariants with nonlinear constraints. This is especially true in programs that perform many numerical operations, such as control systems for avionics or industrial plants. Recently, data-driven methods for loop invariant inference have shown promise, especially on linear invariants. However, applying data-driven inference to nonlinear loop invariants is challenging due to the large numbers of and magnitudes of high-order terms, the potential for overfitting on a small number of samples, and the large space of possible inequality bounds. In this paper, we introduce a new neural architecture for general SMT learning, the Gated Continuous Logic Network (G-CLN), and apply it to nonlinear loop invariant learning. G-CLNs extend the Continuous Logic Network (CLN) architecture with gating units and dropout, which allow the model to robustly learn general invariants over large numbers of terms. To address overfitting that arises from finite program sampling, we introduce fractional sampling---a sound relaxation of loop semantics to continuous functions that facilitates unbounded sampling on real domain. We additionally design a new CLN activation function, the Piecewise Biased Quadratic Unit (PBQU), for naturally learning tight inequality bounds. We incorporate these methods into a nonlinear loop invariant inference system that can learn general nonlinear loop invariants. We evaluate our system on a benchmark of nonlinear loop invariants and show it solves 26 out of 27 problems, 3 more than prior work, with an average runtime of 53.3 seconds. We further demonstrate the generic learning ability of G-CLNs by solving all 124 problems in the linear Code2Inv benchmark. We also perform a quantitative stability evaluation and show G-CLNs have a convergence rate of $97.5\%$ on quadratic problems, a $39.2\%$ improvement over CLN models

Urbach-Wiethe Syndrome and the Ophthalmologist: Review of the Literature and Introduction of the First Instance of Bilateral Uveitis

Patients suffering from Urbach-Wiethe syndrome (UWS), also known as lipoid proteinosis or hyalinosis cutis et mucosae, may have an ophthalmologist involved in the diagnosis and management of their disease. Along with moniliform blepharosis as a pathognomonic feature of the disease, an ophthalmologist may encounter other manifestations of UWS in any part of the eye such as cornea; conjunctiva; sclera; trabecular meshwork; iris/pupil; lens and zonular fibers; retina; nasolacrimal duct. This paper provides a review on the pathogenesis and the diverse ocular manifestations seen in UWS patients. Uncommon complications are discussed in this paper (glaucoma; dry eye and epiphora; complications of lens, retina, cornea; iris/pupil and conjunctiva). Moreover, a 27-year-old male UWS patient is described with bilateral diffuse anterior stromal iris atrophy, diffuse keratic precipitates; posterior subcapsular cataract; 1 + vitreous cell in anterior vitreous examination. This case was thought to be the first instance of bilateral uveitis associated with UWS. Overall, ophthalmologists may encounter diverse ocular complications accompanying this syndrome. They should be familiar with well-established ophthalmologic manifestations leading them to cooperate with other specialists in diagnosis and management of the disease

Phosphoinositide-3 Kinase-Akt Pathway Controls Cellular Entry of Ebola Virus

The phosphoinositide-3 kinase (PI3K) pathway regulates diverse cellular activities related to cell growth, migration, survival, and vesicular trafficking. It is known that Ebola virus requires endocytosis to establish an infection. However, the cellular signals that mediate this uptake were unknown for Ebola virus as well as many other viruses. Here, the involvement of PI3K in Ebola virus entry was studied. A novel and critical role of the PI3K signaling pathway was demonstrated in cell entry of Zaire Ebola virus (ZEBOV). Inhibitors of PI3K and Akt significantly reduced infection by ZEBOV at an early step during the replication cycle. Furthermore, phosphorylation of Akt-1 was induced shortly after exposure of cells to radiation-inactivated ZEBOV, indicating that the virus actively induces the PI3K pathway and that replication was not required for this induction. Subsequent use of pseudotyped Ebola virus and/or Ebola virus-like particles, in a novel virus entry assay, provided evidence that activity of PI3K/Akt is required at the virus entry step. Class 1A PI3Ks appear to play a predominant role in regulating ZEBOV entry, and Rac1 is a key downstream effector in this regulatory cascade. Confocal imaging of fluorescently labeled ZEBOV indicated that inhibition of PI3K, Akt, or Rac1 disrupted normal uptake of virus particles into cells and resulted in aberrant accumulation of virus into a cytosolic compartment that was non-permissive for membrane fusion. We conclude that PI3K-mediated signaling plays an important role in regulating vesicular trafficking of ZEBOV necessary for cell entry. Disruption of this signaling leads to inappropriate trafficking within the cell and a block in steps leading to membrane fusion. These findings extend our current understanding of Ebola virus entry mechanism and may help in devising useful new strategies for treatment of Ebola virus infection

The HIV Envelope but Not VSV Glycoprotein Is Capable of Mediating HIV Latent Infection of Resting CD4 T Cells

HIV fusion and entry into CD4 T cells are mediated by two receptors, CD4 and CXCR4. This receptor requirement can be abrogated by pseudotyping the virion with the vesicular stomatitis virus glycoprotein (VSV-G) that mediates viral entry through endocytosis. The VSV-G-pseudotyped HIV is highly infectious for transformed cells, although the virus circumvents the viral receptors and the actin cortex. In HIV infection, gp120 binding to the receptors also transduces signals. Recently, we demonstrated a unique requirement for CXCR4 signaling in HIV latent infection of blood resting CD4 T cells. Thus, we performed parallel studies in which the VSV-G-pseudotyped HIV was used to infect both transformed and resting T cells in the absence of coreceptor signaling. Our results indicate that in transformed T cells, the VSV-G-pseudotyping results in lower viral DNA synthesis but a higher rate of nuclear migration. However, in resting CD4 T cells, only the HIV envelope-mediated entry, but not the VSV-G-mediated endocytosis, can lead to viral DNA synthesis and nuclear migration. The viral particles entering through the endocytotic pathway were destroyed within 1–2 days. These results indicate that the VSV-G-mediated endocytotic pathway, although active in transformed cells, is defective and is not a pathway that can establish HIV latent infection of primary resting T cells. Our results highlight the importance of the genuine HIV envelope and its signaling capacity in the latent infection of blood resting T cells. These results also call for caution on the endocytotic entry model of HIV-1, and on data interpretation where the VSV-G-pseudotyped HIV was used for identifying HIV restriction factors in resting T cells

Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe