Random Walks and Concurrent Zero-Knowledge

The established bounds on the round-complexity of (black-box) concurrent zero-knowledge (cZK) consider adversarial verifiers with complete control over the scheduling of messages of different sessions. Consequently, such bounds only represent a $\textit{worst}$ case study of concurrent schedules, forcing $\widetilde{\Omega}(\log n)$ rounds for $\textit{all}$ protocol sessions. What happens in average cases against random schedules? Must all sessions still suffer large number of rounds? Rosen and Shelat first considered such possibility, and constructed a cZK protocol that adjusts its round-complexity based on existing network conditions. While they provide experimental evidence for its average-case performance, no provable guarantees are known. In general, a proper framework for studying and understanding the average-case schedules for cZK is missing. We present the first theoretical framework for performing such average-case studies. Our framework models the network as a stochastic process where a new session is opened with probability $p$ or an existing session receives the next message with probability $1-p$; the existing session can be chosen either in a first-in-first-out (FIFO) or last-in-first-out (LIFO) order. These two orders are fundamental and serve as good upper and lower bounds for other simple variations. We also develop methods for establishing provable average-case bounds for cZK in these models. The bounds in these models turn out to be intimately connected to various properties of one-dimensional random walks that reflect at the origin. Consequently, we establish new and tight asymptotic bounds for such random walks, including: expected rate of return-to-origin, changes of direction, and concentration of positive movements. These results may be of independent interest. Our analysis shows that the Rosen-Shelat protocol is highly sensitive to even moderate network conditions, resulting in a large fraction of non-optimal sessions. We construct a more robust protocol by generalizing the footer-free condition of Rosen-Shelat which leads to significant improvements for both FIFO and LIFO models

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Unusual Presentation of Pyogenic Granuloma of Buccal Mucosa

Exophytic growth of the oral cavity often presents a diagnostic challenge because a diverse group of pathologic processes can produce such lesions. Among the exophytic growth of oral cavity inflammatory hyperplasia stands the most common etiology. The pyogenic granuloma is the most common type of inflammatory hyperplasia found in the oral cavity especially in gingiva. Extragingival occurrence of pyogenic granuloma is usually rare. Hence, we report such a rare presentation of pyogenic granuloma on buccal mucosa in a 35-years-old male

Pattern of Oral Lesions in Tuberculosis Patients: A Cross-sectional Study

Introduction: The oral manifestations of tuberculosis forma unique clinical picture. Tuberculosis can occur in the mouth particularly involving the tongue with bizarre and unusual forms. The various manifestations of the oral tubercular lesions produce a distinct pattern of clinical picture and they show a predilection for certain areas of the mouth. Material and methods: This was a cross-sectional study primarily relying on the comparative assessment of the clinical appearance of the lesions found with that of the previously documented and well-described lesions in authoritative books and journals. A thorough case history specific to tuberculosis was gathered by the aid of a specifically structured proforma and a complete oral examination was done with systematic photography. Results: A total of 78 patients were examined, ranging from 13 to 80 years comprising of 69 male and nine female patients. Out of the 78 patients examined, only 57 had oral lesions. Twenty-one patients did not show any mucosal abnormality- Forty-six (60%) patients had pulmonary tuberculosis and 32 (40%) patients had extrapulmonary tuberculosis. Comorbidities present were predominantly diabetes mellitus in 12 patients, HIV infection in four patients, coronary artery disease in two patients, erosive gastric and liver disease in one patient and hypertension in one patient. Conclusion: Apart from the oral lesions that occur in a normal nontuberculosis patient group (the regular lesions) lesions peculiar to the tuberculosis group of patients were recorded. They comprised primarily of lip crusting lesions, ulcerations of buccal mucosa and palate. A soft tissue enlargement was found involving the tongue and the floor of the mouth and was diagnosed as ′primary oral tuberculosis.′ Drug eruptions on the lips due to rifampicin were noted

Strengthening research capacity in LMICs to address the global NCD burden

The burden of noncommunicable diseases (NCDs) continues to rise across the globe, and the risk of dying prematurely from an NCD in a low- and middle-income country (LMIC) is almost double that in a high-income country. Confronting this crisis requires a critical mass of scientists who are well versed in regional health problems and understand the cultural, social, economic, and political contexts that influence the effectiveness of interventions to address NCDs. Investing in research capacity strengthening in LMICs is critical to effectively combating disease, and local researchers are best poised to address the health challenges in their home countries given their understanding of the unique culture and context in which they are working. The Fogarty International Center of the U.S. National Institutes of Health has a set of programs focused on building individual and institutional NCD research capacity in LMICs. The Programs provide models for sustainable scientific research capacity strengthening, innovative funding mechanisms and partnership-building approaches. Investing in the training and scientific capacity of LMIC individuals and institutions not only helps foster a research culture and solidify local ownership of research, but it also ensures that the most appropriate solutions are developed, increasing the likelihood that those solutions will sustain over time. In addition, the Programs’ investigators have advanced the science across a range of NCDs and associated risk factors. This article describes key lessons and compelling cases from the Programs that can be harnessed by other health researchers and funders to further the global response to the NCD burden

Rai1 Haploinsufficiency Is Associated with Social Abnormalities in Mice

Background: Autism is characterized by difficulties in social interaction, communication, and repetitive behaviors; with different degrees of severity in each of the core areas. Haploinsufficiency and point mutations of RAI1 are associated with Smith-Magenis syndrome (SMS), a genetic condition that scores within the autism spectrum range for social responsiveness and communication, and is characterized by neurobehavioral abnormalities, intellectual disability, developmental delay, sleep disturbance, and self-injurious behaviors. Methods: To investigate the relationship between Rai1 and social impairment, we evaluated the Rai1+/− mice with a battery of tests to address social behavior in mice. Results: We found that the mutant mice showed diminished interest in social odors, abnormal submissive tendencies, and increased repetitive behaviors when compared to wild type littermates. Conclusions: These findings suggest that Rai1 contributes to social behavior in mice, and prompt it as a candidate gene for the social behaviors observed in Smith-Magenis Syndrome patients