Making the Most out of Direct-Access Network Attached Storage

The performance of high-speed network-attached storage applications is often limited by end-system overhead, caused primarily by memory copying and network protocol processing. In this paper, we examine alternative strategies for reducing overhead in such systems. We consider optimizations to remote procedure call (RPC)-based data transfer using either remote direct memory access (RDMA) or network interface support for pre-posting of application receive buffers. We demonstrate that both mechanisms enable file access throughput that saturates a 2Gb/s network link when performing large I/Os on relatively slow, commodity PCs. However, for multi-client workloads dominated by small I/Os, throughput is limited by the per-I/O overhead of processing RPCs in the server. For such workloads, we propose the use of a new network I/O mechanism, Optimistic RDMA (ORDMA). ORDMA is an alternative to RPC that aims to improve server throughput and response time for small I/Os. We measured performance improvements of up to 32% in server throughput and 36% in response time with use of ORDMA in our prototype.Engineering and Applied Science

Neutralization, effector function and immune imprinting of Omicron variants

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domai

Assessment of pulmonary artery pressure by echocardiography—A comprehensive review

Pulmonary hypertension is a pathological haemodynamic condition defined as an increase in mean pulmonary arterial pressure ≥ 25mmHg at rest, assessed using gold standard investigation by right heart catheterisation. Pulmonary hypertension could be a complication of cardiac or pulmonary disease or a primary disorder of small pulmonary arteries. Elevated pulmonary pressure (PAP) is associated with increased mortality, irrespective of the aetiology. The gold standard for diagnosis is invasive right heart catheterisation, but this has its own inherent risks. In the past 30 years, immense technological improvements in echocardiography have increased its sensitivity for quantifying pulmonary artery pressure (PAP) and it is now recognised as a safe and readily available alternative to right heart catheterisation. In future, scores combining various echo techniques can approach the gold standard in terms of sensitivity and accuracy, thereby reducing the need for repeated invasive assessments in these patients

Neutralization, effector function and immune imprinting of Omicron variants

Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain$^{1}$ (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 and XBB.1.5 variants bind host ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1, XBB.1 and BN.1 RBDs bound to the fragment antigen-binding region of the S309 antibody (the parent antibody for sotrovimab) and human ACE2 explain the preservation of antibody binding through conformational selection, altered ACE2 recognition and immune evasion. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1 and hamsters challenged with XBB.1.5. Vaccine-elicited human plasma antibodies cross-react with and trigger effector functions against current Omicron variants, despite a reduced neutralizing activity, suggesting a mechanism of protection against disease, exemplified by S309. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring the role of persistent immune imprinting

3D echocardiographic reference ranges for normal left ventricular volumes and strain: Results fromthe EACVI NORRE study

Aim To obtain the normal ranges for 3D echocardiography (3DE) measurement of left ventricular (LV) volumes, function, and strain from a large group of healthy volunteers. Methods and results A total of 440 (mean age: 45613 years) out of the 734 healthy subjects enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study had good-quality 3DE data sets that have been analysed with a vendor-independent software package allowing homogeneous measurements regardless of the echocardiographic machine used to acquire the data sets. Upper limits of LV end-diastolic and end-systolic volumes were larger in men (97 and 42 mL/m2) than in women (82 and 35 mL/m2; P<0.0001). Conversely, lower limits of LV ejection fraction were higher in women than in men (51% vs. 50%; P<0.01). Similarly, all strain components were higher in women than in men. Lower range was -18.6% in men and -19.5% in women for 3D longitudinal strain, -27.0% and -27.6% for 3D circumferential strain, -33.2% and -34.4% for 3D tangential strain and 38.8% and 40.7% for 3D radial strain, respectively. LV volumes decreased with age in both genders (P<0.0001), whereas LV ejection fraction increased with age only in men. Among 3DE LV strain components, the only one, which did not change with age was longitudinal strain. Conclusion The NORRE study provides applicable 3D echocardiographic reference ranges for LV function assessment. Our data highlight the importance of age- and gender-specific reference values for both LV volumes and strain. All rights reserved

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant–neutralizing antibody that is a strong candidate for clinical development

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development