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To date, there is no standard treatment regimen for carbonic anhydrase inhibitors (CAIs) in X-linked retinoschisis (XLRS) patients. This retrospective study aims to evaluate the efficacy of CAIs on visual acuity and cystoid fluid collections (CFC) in XRLS patients in Dutch and Belgian tertiary referral centers.

This article presents a wideband blocker tolerant receiver (RX) for fifth-generation (5G) user equipment applications. Two programmable zeros around the channel bandwidth are introduced to sufficiently suppress the close-in blockers of 5G applications. Since the effect of zeros gradually diminishes at larger out-of-band offset frequencies, an auxiliary current-sinking path is also introduced to reduce the RX input impedance at far-out offset frequencies. Moreover, a simple second-order transimpedance amplifier (TIA) is adopted to enhance the proposed RX selectivity. The utilized TIA synthesizes two complex conjugate poles to achieve a flat gain response and −40 dB/dec roll-off. A 40-nm CMOS RX prototype occupies 1.15mm2 and consumes 84–140mW from a 1.3-V supply voltage over the 0.5–3-GHz operating frequency range. The RX achieves a 160-MHz RF bandwidth, 2.6–4.2-dB noise figure, a −0.3-dBm blocker 1-dB compression point (B1dB), and an out-of-band third-order intercept point (IIP3) of 22.5 dBm. As a test case, using the 3GPP standard, a −15-dBm continuous wave (CW) close-in out-of-band blocker located at 85-MHz offset from the passband edges is applied to the RX. Thanks to the receiver’s high selectivity, the RX achieves 100% throughput while detecting 100-MS/s quadrature phase shift keying (QPSK) signal with 16 dB higher power than the reference sensitivity.

The RF performance of current-scaling digital transmitters (DTX) with polar, unsigned Cartesian, signed Cartesian, and multiphase architectures have been compared regarding power utilization of their output-stage switch banks and drain efficiency. The analysis includes various switch bank operation modes, such as switch bank sharing, segment activation interleaving, and their activation times (RF duty cycle of the segments). Current-scaling DTXs can be made compatible with high-power operations while offering high system efficiency and RF bandwidth. The average efficiency using Doherty power back-off efficiency enhancement is analyzed, and a comparison of the different proposed DTX implementations is presented.

Emotional intelligence (EI) supports the clinical and social competencies of a practicing dentist. Reuven Bar‐On's EI model is an array of inter‐related emotional and social competencies, skills, and behaviors, which consist of five key domains: Self‐Perception, Self‐Expression, Interpersonal, Decision Making, and Stress Management, and associated with the domains are 15 emotional quotient (EQ) subskills. This study measured the impact of COVID‐19 on dental students' EI by comparing measures pre‐COVID‐19 and during COVID‐19 matriculation. This retrospective longitudinal study measured EI with the EQ‐i 2.0 for higher education. Dental students completed an EQ‐i 2.0 assessment (Attempt) at the beginning of matriculation, at the mid‐point, and prior to graduation. Ten groups were included, of which the first three completed matriculation prior to the pandemic and the remaining seven matriculated during timeframes intersecting at different times during the pandemic. A paired t‐test dependent sample of means (p≤ 0.05) compared EQ scores for each attempt for all groups. The study compared means for three EQ attempts with the t‐test independent sample of means (p≤ 0.05) for cohorts matriculating pre‐COVID‐19 and during COVID‐19. The pre‐COVID‐19 groups showed significant increases in EQ with each subsequent attempt. COVID‐19‐impacted groups demonstrated significant increase in Stress Tolerance and significant decreases, most notably in the domains of Interpersonal and Self‐Perception, and subscales of Optimism and Happiness. COVID‐19‐related stressors impacted dental students’ EI as multiple EI areas declined significantly. Dental educators should minimize organizational stressors and support EI during years 2 and 3 of matriculation.

A current-mode direct-digital RF modulator (DDRM)-based transmitter (TX) architecture is proposed in this article for energy-efficient wireless applications. To demonstrate its key principles, a 2×13 bit demonstrator is implemented in a 40-nm CMOS technology. This DDRM can operate standalone or as a driver for a common-gate (CG)/common-base (CB) power amplifier (PA). The proposed DDRM is based on current-steering radio frequency digital-to-analog converters (RFDACs) that feature an extra current division path to allow the generation of the optimum current-mode class-B drive profile for the final CG/CB PA, facilitating energy-efficient TX operation without compromising linearity. For this purpose, the DDRM uses signed-IQ mapping combined with a class-B harmonic rejection (HR) technique. In addition, an advanced dynamic biasing technique is introduced to further enhance the TX line-up efficiency in deep power back-off (PBO) region. The DDRM driver standalone can provide 19.6-dBm RF peak output power. It supports a “160-MHz 256-QAM” signal at 2.4 GHz with an adjacent channel leakage ratio (ACLR) of −40.3 dBc and an error vector magnitude (EVM) of −33 dB, without using any digital pre-distortion (DPD). When connected to a CB SiGe PA, the overall TX line-up achieves an output power of 27 dBm and an overall TX system efficiency of 20%. This DPD-free TX line-up achieves an ACLR of −37.7 dBc and an EVM of −30 dB, respectively, when operating with an “80-MHz 64-QAM” signal at 2.2 GHz.

Chronic pain after spine surgery (CPSS) is often characterized by intractable low back pain and/or radiating leg pain, and has been reported in 8–40% of patients that received lumbar spine surgery. We conducted a literature search of PubMed, MEDLINE/OVID with a focus on studies about the etiology and treatments of CPSS and low back pain. Our aim was to provide a narrative review that would help us better understand the pathogenesis and current treatment options for CPSS. This knowledge will aid in the development of optimal strategies for managing postoperative pain symptoms and potentially curing the underlying etiologies. Firstly, we reviewed recent advances in the mechanistic study of CPSS, illustrated both structural (e.g., fibrosis and scaring) and non-structural factors (e.g., inflammation, neuronal sensitization, glial activation, psychological factor) causing CPSS, and highlighted those having not been given sufficient attention as the etiology of CPSS. Secondly, we summarized clinical evidence and therapeutic perspectives of CPSS. We also presented new insights about the treatments and etiology of CPSS, in order to raise awareness of medical staff in the identification and management of this complex painful disease. Finally, we discussed potential new targets for clinical interventions of CPSS and future perspectives of mechanistic and translational research. CPSS patients often have a mixed etiology. By reviewing recent findings, the authors advocate that clinicians shall comprehensively evaluate each case to formulate a patient-specific and multi-modal pain treatment, and importantly, consider an early intraoperative intervention that may decrease the risk or even prevent the onset of CPSS.

By introducing three different techniques, this article, for the first time, presents a wideband highly linear receiver (RX) capable of handling blocking scenarios in fifth-generation (5G) microcell base station applications. First, a parallel preselect filter is introduced to satisfy the base station co-location blocking requirements. Next, a combination of third-order RF and baseband (BB) filters is adopted to attenuate close-in blockers by a −120 dB/dec roll-off. Finally, a translational feedback network is proposed to reduce the in-band gain ripple to below 0.5 dB and provide better than −19 dB input matching. Fabricated in the 40-nm CMOS technology, the proposed RX occupies a core area of 0.8 $\mathrm {\mathbf {mm^{2}}}$ and consumes 108–176 mW from a 1.3 V supply over the RX’s 0.5–3-GHz operating frequency. It achieves a 3-dB bandwidth of 150 MHz and a noise figure (NF) of 2.6–3.9 dB over the RX frequency range. Activating the parallel preselect filter degrades the NF by as little as 1.2 dB in the worst case. The RX shows a $\geq $ 97.5% throughput when receiving a 100-MS/s quadrature phase shift keying (QPSK) signal with 7.5-dB SNR and achieves a −9.7 dB error vector magnitude (EVM) while facing a −15 dBm continuous-wave (CW) blocker only 20 MHz away from the desired 100-MS/s QPSK signal with 12.3-dB SNR, thus satisfying the 3rd generation partnership project (3GPP) requirements with sufficient margin.

HIV-1 Gag metamorphoses inside each virion, from an immature lattice that forms during viral production to a mature capsid that drives infection. Here we show that the immature lattice is required to concentrate the cellular metabolite inositol hexakisphosphate (IP6) into virions to catalyze mature capsid assembly. Disabling the ability of HIV-1 to enrich IP6 does not prevent immature lattice formation or production of the virus. However, without sufficient IP6 molecules inside each virion, HIV-1 can no longer build a stable capsid and fails to become infectious. IP6 cannot be replaced by other inositol phosphate (IP) molecules, as substitution with other IPs profoundly slows mature assembly kinetics and results in virions with gross morphological defects. Our results demonstrate that while HIV-1 can become independent of IP6 for immature assembly, it remains dependent upon the metabolite for mature capsid formation.

The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. Although first-generation vaccines remain effective against severe disease and death, robust evidence on vaccine effectiveness (VE) against all Omicron infections, irrespective of symptoms, remains sparse. We used a community-wide serosurvey with 5,310 subjects to estimate how vaccination histories modulated risk of infection in infection-naive Hong Kong during a large wave of Omicron BA.2 epidemic in January–July 2022. We estimated that Omicron infected 45% (41–48%) of the local population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection 7 days after vaccination (VE of 48% (95% credible interval 34–64%) and 69% (46–98%) for three and four doses of BNT162b2, respectively; VE of 30% (1–66%) and 56% (6–97%) for three and four doses of CoronaVac, respectively). At 100 days after immunization, VE waned to 26% (7–41%) and 35% (10–71%) for three and four doses of BNT162b2, and to 6% (0–29%) and 11% (0–54%) for three and four doses of CoronaVac. The rapid waning of VE against infection conferred by first-generation vaccines and an increasingly complex viral evolutionary landscape highlight the necessity for rapidly deploying updated vaccines followed by vigilant monitoring of VE.

While finite-difference time-domain methods have long been the foundational basis for particle-in-cell (PIC) codes, there has been increasing momentum in developing a suite of finite element-based PIC methods. The beauty of finite difference-based methods is that it is easily cast within the correct mathematical framework to represent fields, fluxes, currents, and charges. However, more importantly, these methods are cost-effective. In the intervening years, since finite difference methods were developed, the state of the art of field modeling has shifted rather dramatically. Indeed, the most popular and trusted field simulators are based on the finite element method (FEM), thanks, in large part, to the discovery of the correct function spaces for quantities of interest for Maxwell’s equations, but also the flexibility that it brings to modeling geometry with the ability to refine in space and numerical order to better capture the underlying physics. Together with time-stepping schemes that are unconditionally stable, these methods provide the framework necessary to correctly capture the nuance of the physical evolution with high fidelity. The intent of this article is to review advances in electromagnetic finite element PIC (EM-FEMPIC). We will address the progress made in fundamental challenges in such a method for charge conservation to more programmatic ones, such as computational complexity.

The state of art of charge conserving electromagnetic finite element particle-in-cell (EM-FEMPIC) has grown by leaps and bounds in the past few years. These advances have primarily been achieved for leap-frog time stepping schemes for Maxwell solvers, in large part, due to the method strictly following the proper space for representing fields, charges, and measuring currents. Unfortunately, leap-frog-based solvers (and their other incarnations) are only conditionally stable. Recent advances have made it possible to construct EM-FEMPIC methods built around unconditionally stable time-stepping methods while conserving charge. Together with the use of a quasi-Helmholtz decomposition, these methods were both unconditionally stable and satisfied Gauss’ laws to machine precision. However, this architecture was developed for systems with explicit particle integrators where fields and velocities were off by a time step. While completely self-consistent methods exist in the literature, they follow the classic rubric: collect a system of first-order differential equations (Maxwell and Newton equations) and use an integrator to solve the combined system. These methods suffer from the same side effect as earlier—they are conditionally stable. Here, we propose a different approach; we pair an unconditionally stable Maxwell solver to an exponential predictor corrector (PC) method for Newton’s equations. As we will show via numerical experiments, the proposed method conserves energy within a particle-in-cell (PIC) scheme, has an unconditionally stable electromagnetic (EM) solve, solves Newton’s equations to much higher accuracy than a traditional Boris solver, and conserves charge to machine precision. We further demonstrate benefits compared with other polynomial methods to solve Newton’s equations, like the well-known Boris push.

This article presents a wideband, energy-efficient digital transmitter (DTX) suitable for multi-mode/multi-band wireless communication applications. It features various operation modes comprising Cartesian (Modes-1/-2) and multi-phase (Modes-3/-4) configurations utilizing LO clocks with different duty cycle in the interleaving/non-interleaving configurations. The multi-phase operation compromises polar and Cartesian features by mapping the $I/Q$ signals into two non-orthogonal basis vectors with a 45° relative phase difference and a 3-bit phase selector scheme. The different operation modes are extensively analyzed and compared. Fabricated in a 40-nm CMOS process with an off-chip matching network, the proposed DTX occupies a core area of 0.72 mm2 and delivers 23.18-dBm RF peak power at 2.1 GHz from a 0.95-V supply voltage with drain/system efficiencies of 66.26%/52.59%, respectively. Utilizing a simple memory-less digital pre-distortion (DPD) for a 160-MHz four-channel 64-quadrature amplitude modulation (QAM) orthogonal frequency-division multiplexing (OFDM) signal, the DTX delivers an average $P _{\text {Out}}$ of 13.5/11.4/7.7/9.4 dBm, achieving an adjacent channel (power) ratio (ACL(P)R) of better than −42/−40/−40/−38 dBc and an average error vector magnitude (EVM) of −36/−34/−34/−32 dB, operating in Modes-1/-2/-3/-4, respectively. While transmitting a 200-MHz single-channel 256 (1024)-QAM OFDM signal at 2.4 GHz in Modes-1/-4, the average delivered output power is 14.11/9.29 (12.23/7.32) dBm with average drain and system efficiencies of 33.17%/26.3% (23.82%/22.83%) and 24.81%/22.85% (19.34%/18.81%), while the ACLR and EVM are better than −42/−41 (−43/−43) dBc and −34.6/−33.1 (−33.5/−33.9) dB, respectively.

The analysis of electromagnetic (EM) scattering in the isogeometric analysis (IGA) framework based on the Loop subdivision has long been restricted to simply connected geometries. The inability to analyze multiply connected objects is a glaring omission. In this article, we address this challenge. IGA provides seamless integration between the geometry and analysis using the same basis set to represent both. In particular, IGA methods using subdivision basis sets exploit the fact that the basis functions used for surface description are smooth (with continuous second derivatives) almost everywhere. On simply connected surfaces, this permits the definition of basis sets that are divergence-free and curl-free. What is missing from this suite is a basis set that is both divergence-free and curl-free, a necessary ingredient for a complete Helmholtz decomposition of currents on multiply connected structures. In this article, we achieve this missing ingredient numerically using random polynomial vector fields. We show that this basis set is analytically divergence-free and curl-free. Furthermore, we show that these bases recover curl-free, divergence-free, and both curl-free and divergence-free fields. Finally, we use this basis set to discretize a well-conditioned integral equation for analyzing perfectly conducting objects and demonstrate excellent agreement with other methods.

Located just outside of Naval Weapons Station (WPNSTA) Yorktown, along Old Williamsburg Road, Route 238, near Lebanon Church and Endview Plantation, stands a Virginia highway historical marker -- a constant [...]

Covalent inhibitors are viable therapeutics. However, off-target reactivity challenges the field. Chemists have attempted to solve this issue by varying the reactivity attributes of electrophilic warheads. Here, we report the development of an approach to increase the selectivity of covalent molecules that is independent of warhead reactivity features and can be used in concert with existing methods. Using the scaffold of the Bruton’s tyrosine kinase (BTK) inhibitor Ibrutinib for our proof-of-concept, we reasoned that increasing the steric bulk of fumarate-based electrophiles on Ibrutinib should improve selectivity via the steric exclusion of off-targets but retain rates of cysteine reactivity comparable to that of an acrylamide. Using chemical proteomic techniques, we demonstrate that elaboration of the electrophile to a tert-butyl (t-Bu) fumarate ester decreases time-dependent off-target reactivity and abolishes time-independent off-target reactivity. While an alkyne-bearing probe analogue of Ibrutinib has 247 protein targets, our t-Bu fumarate probe analogue has only 7. Of these 7 targets, BTK is the only time-independent target. The t-Bu inhibitor itself is also more selective for BTK, reducing off-targets by 70%. We investigated the consequences of treatment with Ibrutinib and our t-Bu analogue and discovered that only 8 proteins are downregulated in response to treatment with the t-Bu analogue compared to 107 with Ibrutinib. Of these 8 proteins, 7 are also downregulated by Ibrutinib and a majority of these targets are associated with BTK biology. Taken together, these findings reveal an opportunity to increase cysteine-reactive covalent inhibitor selectivity through electrophilic structure optimization.

Half-dose photodynamic therapy leads to a significantly larger decrease in the height of the highest macular pigment epithelial detachment compared with high-density subthreshold micropulse laser treatment in chronic central serous chorioretinopathy.

Modeling is a central skill in scientific reasoning. Learning to formulate, analyze, test, and revise models is a crucial aspect of understanding science and is critical to helping students become […], Learning how to create, test, and revise models is a central skill in scientific reasoning. We argue that qualitative modeling provides an appropriate level of representation for helping middle-school students learn to become modelers. We describe Vmodel, a system we have created that uses visual representations and that enables middle-school students to create qualitative models. Software coaches use simple analyses of model structure plus qualitative simulation to provide feedback and explanations. This system has been used in several studies in Chicago public school classrooms, using curricula developed in collaboration with teachers. We discuss the design of the visual representation language, how Vmodel works, and evidence from school studies that indicate it is successful in helping students.

Study objectives: Multiple risk factors for mortality in patients with COPD have been described, but most studies have involved older, primarily male subjects. The purpose of this study was to [...]

AbstractMantids are influential generalist predators in terrestrial systems. Therefore, large mantid species like the European mantid, Mantis religiosa(Linnaeus, 1758), are often used by humans and purposefully introduced as a form of biocontrol, greatly expanding their geographic ranges. However, mantids are rarely recorded in marine systems. In this study, we present an observation of European mantids living in a salt marsh and actively moulting in the vegetation in Elkhorn Slough, in Monterey Bay, California, United States of America. Not only are these European mantids a nonnative species, but every observed individual was a flightless juvenile, meaning they hatched nearby. Although mantids are not usually associated with intertidal ecosystems, there are multiple potential reasons that mantids would be drawn to salt marshes, including food, potential for camouflage, and lower predation pressure. The addition of a generalist predator could produce a complex mix of positive and negative impacts on the marsh itself and, given the importance of marsh systems, these possible effects warrant further study.

We report here our experience in achieving remission in a 20-year-old man with pulmonary capillary hemangiomatosis (PCH) with atypical endotheliomatosis following therapy with doxycycline. PCH is a rare disorder characterized [...]

Objectives: To assess left ventricular systolic and diastolic function in adult patients with cystic fibrosis using radionuclide ventriculography. Background: Although myocardial fibrosis has been described in autopsy specimens of patients [...]

AbstractIn this case study, we demonstrate the use of multilevel process monitoring in quality control. Using high school data, we answer three research questions related to high school student progress during an academic year. The questions are (1) What determines student performance? (2) How can statistical process monitoring be used in monitoring student progress? (3) What method can be used for predictive monitoring of student results? To answer these questions, we worked together with a Dutch high school and combined hierarchical Bayesian modeling with statistical and predictive monitoring procedures. The results give a clear blueprint for student progress monitoring.

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.

The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT50) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3–5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT50titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed.

ABSTRACTLocal farmers’ engagement and contributions are increasingly underscored in resources restoration policy. Yet, empirical context-situated understanding of the environmental impacts of farmer-led restoration remains scant. Using six Agent-based Modeling (ABM) simulations that integrate multi-type data, we explore the potential spatial-temporal aggregate patterns and outcomes of local restoration actions in Central Malawi. Findings uncover a 10-year positive trend and spatially explicit potential restoration extent and intensity, greenness, and land productivity, all varying by farmer’s participation level. Landscape regreening is modestly promising with fluctuating greenness levels and low, slightly incremental, then steady land-productivity levels. Findings also show appropriate incentives, restoration knowledge, and inspiring local leadership as propitious management options for boosting local restoration. Bundling these enabling management and policy options would maximize local restoration. Findings suggest empowering bottom-up restoration efforts for enhanced environmental impacts. We also demonstrate the potential of using ABM to offer insights for spatially targeted, evidence-based restoration policy implementation and monitoring.

Study objectives: We tested the hypothesis that breathing 100% oxygen could result in selective pulmonary vasodilatation in patients with pulmonary hypertension, including those patients who would not meet current Health [...]

ABSTRACTGuanylyl cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of the luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Previous studies revealed that linaclotide, an oral GUCY2C agonist formulated for gastric release, did not persist to activate guanylyl cyclase signaling in the distal rectum. Dolcanatide is an investigational oral uroguanylin analog, substituted with select D amino acids, for enhanced stability and extended persistence to activate GUCY2C in small and large intestine. However, the ability of oral dolcanatide to induce a pharmacodynamic (PD) response by activating GUCY2C in epithelial cells of the colorectum in humans remains undefined. Here, we demonstrate that administration of oral dolcanatide 27 mg daily for 7 d to healthy volunteers did not activate GUCY2C, quantified as accumulation of its product cyclic GMP, in epithelial cells of the distal rectum. These data reveal that the enhanced stability of dolcanatide, with persistence along the rostral-caudal axis of the small and large intestine, is inadequate to regulate GUCY2C across the colorectum to prevent tumorigenesis. These results highlight the importance of developing a GUCY2C agonist for cancer prevention formulated for release and activity targeted to the colorectum.

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

In chronic central serous chorioretinopathy, half-dose photodynamic therapy may lead to significant changes of the choroid, including a reduction in the area of hyperfluorescence on indocyanine green angiography and decrease in choroidal thickness. High-density subthreshold micropulse laser does not significantly affect these parameters.

Bilateral volume reduction surgery (VRS) improves lung function for selected patients with emphysema. However, predictors of outcome are not well defined. We reviewed the preoperative characteristics of the first 47 consecutive patients who underwent bilateral VRS at the Massachusetts General Hospital in order to define potential predictors of unacceptable outcome. Preoperative data included spirometry, plethysmography, diffusion of carbon monoxide (Dco), maximum inspiratory pressure (MIP), maximum expiratory pressure, resting arterial blood gases (ABG), cardiopulmonary exercise testing with ABG and lactate sampling, and radionuclide ventriculography. Prepulmonary and postpulmonary rehabilitation 6-min walk tests (6MWT), and preoperative chest CT scans were also obtained. Twenty-two subjects were male and 17 of the subjects were on the lung transplant list. Patient characteristics included age of 60.5 ± 7.5 years, [FEV.sub.]1 of 0.67 ± 0.20 L, total lung capacity of 7.56 ± 1.7 L, Dco of 7.40 ± 4.1 mL/min/mm Hg, and Pa[CO.sub.2] of 41.6 ± 6.4 mm Hg (mean ± SD). The [FEV.sub.1], vital capacity, MIP, resting room air [PaCO.sub.2], prepulmonary and postpulmonary rehabilitation 6MWT, and [PaCO.sub.2] at maximum oxygen consumption correlated with length of hospitalization (p [is less than] 0.05). Based on analysis of 41 of 47 patients for whom there were complete data, the inability to walk more than 200 m on the 6MWT before or after preoperative pulmonary rehabilitation, and resting [PaCO.sub.2] [is greater than or equal to] 45 mm Hg were the best predictors of an unacceptable outcome. If either of these characteristics was present, six of 16 vs zero of 25 died (Fisher's Exact Test, p=0.0025, one-tailed) and 11 of 16 vs four of 25 had hospital courses [is greater than] 21 days (p [is less than] 0.002). Both the 6MWT [is less than] 200 m and resting [PaCO.sub.2] [is greater than or equal to] 45 mm Hg alone correlated with death (p=0.004 and p=0.012, respectively) and the resting [PaCO.sub.2] [is greater than or equal to] 45 mm Hg correlated with hospital days [is greater than] 21 (p=0.0002). In conclusion, the data suggest that the inability to walk at least 200 m in 6 min before or after pulmonary rehabilitation and a resting room air [PaCO.sub.2] [is greater than or equal to] 45 mm Hg are excellent preoperative predictors of unacceptable postoperative outcomes. (CHEST 1997, 111:550-58) Key words: bilateral pneumoplasty; COPD; emphysema; pneumoplasty; preoperative; volume reduction surgery Abbreviations: ABG=arterial blood gas; CPEx=cardiopulmonary exercise test; Dco=diffusion of carbon monoxide; HR=heart rate; MEP=maximum expiratory pressure; MIP=maximum inspiratory pressure; MVV=maximum voluntary ventilation; PFT=pulmonary function test; VC=vital capacity; VE=minute ventilation; [Vo.sub.2]=oxygen consumption; [Vo.sub.2]max=maximum oxygen consumption; VRS=volume reduction surgery; 6MWT=6-min walk test, It has been estimated that more than 15 million patients in the United States are afflicted with COPD.[1] Therapeutic options have included Β-adrenergic and anticholinergic agents, oxygen, steroids, rehabilitation, bullectomy, [...]

Introduction: In early 2020, at first surge of the coronavirus disease 2019 (COVID-19) pandemic, many health care workers (HCW) were re-deployed to critical care environments to support intensive care teams looking after patients with severe COVID-19. There was considerable anxiety of increased risk of COVID-19 for these staff. To determine whether critical care HCW were at increased risk of hospital acquired infection, we explored the relationship between workplace, patient facing role and evidence of immune exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a quaternary hospital providing a regional critical care response. Routine viral surveillance was not available at this time.

To be effective in making your case to people who have a different thinking style, you must learn to recognize their style and adjust your presentation accordingly. In the last [...]

Background. Hepatitis B virus (HBV) infections are a serious health problem in the United States, where approximately 18,000 cases are reported each year to the Centers for Disease Control. Even among health care providers, reported vaccination rates have ranged from 17% to 68%. The purpose of this study was to determine the important factors influencing physicians in an academic medical center to receive the HBV vaccination since the introduction of recombinant yeast-derived vaccines. Methods. The 1282 house staff and attending physicians in a university medical center were surveyed regarding their HBV vaccination history. The characteristics of vaccinated and nonvaccinated physicians and their attitudes and concerns regarding vaccination were compared. Results. Of the 813 physicians who responded, 54.0% had been vaccinated. Vaccination rates varied with level of training, from 91.9% among first- and second-year residents to 32.2% among attending physicians. Although physicians in specialties at higher risk for infection were more likely to have been vaccinated, only 40.0% of pathologists and 51.9% of obstetrician-gynecologists reported having been vaccinated. Using multi-variate analysis, we found important demographic predictors of HBV vaccination included physician sex and years since graduation, as well as level of training and specialty. Physicians who had been offered the vaccine were more likely to have been vaccinated. Conclusions. These results show that many physicians in an academic medical center, particularly those at an early stage of their training, have received HBV vaccination. Our results suggest that programs offering hepatitis B vaccinations to physicians can be effective in reducing this group&apos;s risk of hepatitis B infections. Special efforts may be necessary to reach physicians who have completed their training., Hepatitis B virus (HBV) infections remain an important health problem in the United States, where approximately 18,000 cases are reported each year to the Centers for Disease Control. The actual [...]

As pressure on the medical community to provide cost-effective medically appropriate care in an era of constrained resources has mounted in recent years, examining variations in medical practice has received [...]

To describe phenotypic, genotypic, and histopathological features of inherited retinal dystrophies associated with the CRXgene (CRX-RDs).

Interleukin-2 (IL-2) is a growth factor that is released by immune T cells when these cells are activated by lectin, a plant protein that can provoke an immune response. The activation of T cells involves the expression of IL-2 receptors (IL-2R), or protein sites on the cell membrane that specifically bind IL-2. The attachment of IL-2 to its receptors activates a series of events leading to the growth and differentiation of the T cell. Studies show that various immune cells, including T cells, express the IL-2R and release the soluble form of IL-2R (sIL-2R). The blood levels of sIL-2R are increased in patients with various disorders, including leukemia; infection with the human immunodeficiency virus; various lung disorders; rheumatoid arthritis, an inflammatory joint disease; systemic lupus erythematosus, a chronic inflammatory disease of connective tissue; and heart, liver, or kidney transplant rejection. The levels of sIL-2R have not been measured in patients with lung cancer or in smokers, although patients with lung cancer have been shown to have activated T cells. To learn more about interleukin-2 in smokers, the levels of sIL-2R were measured in smokers and patients with lung cancer. The results show that smokers and lung cancer patients have elevated levels of sIL-2R as compared with nonsmokers and healthy persons. Among patients with the squamous cell carcinoma (SCC) type of lung cancer, sIL-2R levels were highest in those without symptoms but with well-differentiated tumors. Patients with SCC and tumors less than three centimeters in diameter had higher sIL-2R levels than SCC patients with tumors greater than three centimeters in diameter. The sIL-2R level correlated with the stage of tumor development, with the highest levels evident among patients with stage 1 cancer. Hence in patients with SCC, the sIL-2R level served as an indicator of the degree of malignancy. These findings suggest that sIL-2R may be involved in the immune abnormalities associated with smoking and lung cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)