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Negative symptoms and cognitive deficits contribute strongly to disability in schizophrenia, and are resistant to existing medications. Recent drug development has targeted enhanced NMDA function by increasing mGluR2/3 signaling. However, the clinical utility of such agents remains uncertain, and markers of brain circuit function are critical for clarifying mechanisms and understanding individual differences in efficacy. We conducted a double-blind, placebo-controlled, randomized cross-over (14 day washout) pilot study evaluating adjunctive use of the mGluR2 positive allosteric modulator AZD8529 (80 mg daily for 3 days), in chronic stable patients with schizophrenia (n = 26 analyzed). We focused on 3 T fMRI response in frontostriatal regions during an n-back working memory task, testing the hypothesis that AZD8529 produces fMRI changes that correlate with improvement in negative symptoms and cognition. We found that AZD8529 did not produce significant group-average effects on symptoms or cognitive accuracy. However, AZD8529 did increase n-back fMRI activation in striatum (p < 0.0001) and anterior cingulate/paracingulate (p = 0.002). Greater drug-versus-placebo effects on caudate activation significantly correlated with greater reductions in PANSS negative symptom scores (r = -0.42, p = 0.031), and exploratory correlations suggested broader effects across multiple symptom domains and regions of interest. These findings demonstrate that fMRI responses to mGluR2 positive modulation relate to individual differences in symptom reduction, and could be pursued for future biomarker development. Negative clinical results at the group level should not lead to premature termination of investigation of this mechanism, which may benefit an important subset of individuals with schizophrenia. Imaging biomarkers may reveal therapeutic mechanisms, and help guide treatment toward specific populations.

Ever since the severe acute respiratory syndrome virus causing coronavirus disease 2019 (COVID-19) struck the world, global health strategies have changed significantly. According to the Centers for Disease Control and Prevention, kidney transplant recipients are stratified as being high risk of developing fatal illness from COVID-19 infection. Kidney transplant is the gold-standard treatment for end-stage kidney disease subjects. During the pandemic, significant concerns have emerged regarding continuation of kidney transplant surgeries and management of kidney transplant recipients post-transplant. The added risk of immunosuppression in this cohort was and remains a theoretical concern, posing a potential risk of transplantation rather than benefit. This comprehensive review aims to cover most of the faced challenges in kidney transplantation in different stages of the pandemic. In addition, it will elucidate the epidemiology, nature, course of the disease, surgical consideration in donors and recipients as well as role of immunosuppression and management of COVID-19 infected kidney transplant recipients during these extraordinary circumstances.

With the COVID-19 outbreak severely overwhelming healthcare systems worldwide, countries must decide on allocation criteria for scarce intensive care resources such as ventilators, leaving some without life-saving treatment. Groups such as the Italian College of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) have suggested using age as allocation criteria, prioritizing the young over the elderly. In judging the morality of such criteria, different ethical frameworks must be applied. From a utilitarian perspective, age-based allocation ensures “the greatest good” – that those with greater “therapeutic success” or “quality-of-life” get access to intensive treatment. However, age poorly predicts prognostic outcomes, and quality-of-life measures are inherently value-laden. From a contractarian view, a morally justifiable action is one made in ignorance of one’s own stake in the outcome. In this lens, age-based allocation is justified since it maximizes the most life-years for the most people. However, it relies on the same flawed assumptions as utilitarianism. From a prioritarian view, age-based allocation ensures that the rights of the young to live out a “normal life span” are respected. However, such judgements ignore the positive experiences of later life and cannot be made on a patient’s behalf. Through a deontological lens, age-based allocation is discriminatory as it views elderly people as means to an end rather than individual agents. Ultimately, the rationing criteria a society uses reflects its values, with age limitations implicitly devaluating the elderly. Therefore, allocation guidelines should deemphasize age in favor of more predictive and less discriminatory measures like multimorbidity or frailty.

Negative symptoms and cognitive deficits contribute strongly to disability in schizophrenia, and are resistant to existing medications. Recent drug development has targeted enhanced NMDA function by increasing mGluR2/3 signaling. However, the clinical utility of such agents remains uncertain, and markers of brain circuit function are critical for clarifying mechanisms and understanding individual differences in efficacy. We conducted a double-blind, placebo-controlled, randomized cross-over (14 day washout) pilot study evaluating adjunctive use of the mGluR2 positive allosteric modulator AZD8529 (80 mg daily for 3 days), in chronic stable patients with schizophrenia (n = 26 analyzed). We focused on 3 T fMRI response in frontostriatal regions during an n-back working memory task, testing the hypothesis that AZD8529 produces fMRI changes that correlate with improvement in negative symptoms and cognition. We found that AZD8529 did not produce significant group-average effects on symptoms or cognitive accuracy. However, AZD8529 did increase n-back fMRI activation in striatum (p 0.0001) and anterior cingulate/paracingulate (p = 0.002). Greater drug-versus-placebo effects on caudate activation significantly correlated with greater reductions in PANSS negative symptom scores (r = -0.42, p = 0.031), and exploratory correlations suggested broader effects across multiple symptom domains and regions of interest. These findings demonstrate that fMRI responses to mGluR2 positive modulation relate to individual differences in symptom reduction, and could be pursued for future biomarker development. Negative clinical results at the group level should not lead to premature termination of investigation of this mechanism, which may benefit an important subset of individuals with schizophrenia. Imaging biomarkers may reveal therapeutic mechanisms, and help guide treatment toward specific populations.

Hydrogen is a major industrial chemical whose manufacture is responsible for ∼3% of global carbon dioxide emissions. >95% of hydrogen is made via reforming fossil fuels which typically co-produces hydrogen and waste carbon dioxide. Nearly all other hydrogen is co-produced with other commodity chemicals. Unfortunately, many alternative, clean hydrogen production processes are small-scale because they require major reductions in capital cost or energy prices to be economical enough for industry. Because the climate problem is urgent, and the economics of future energy is uncertain, this paper seeks to expand the options for producing industrial-scale, clean hydrogen under common, present-day economic conditions. First, we build a model to understand the economic and carbon dioxide emissions constraints of sulfur electrolysis which is an emerging process that cogenerates hydrogen and co-salable sulfuric acid and has the potential to produce up to 36% of the world's current hydrogen demand under present-day, average US economic conditions. We also use our model to evaluate water electrolysis, which cogenerates hydrogen and waste oxygen, but is not economical under present-day average US economic conditions. We then propose criteria for identifying clean hydrogen production chemistries. Using these criteria, we find enough reactions to have the combined potential to make over 150% of the world's industrial hydrogen needs under present-day, average US economic conditions while reducing cost and reducing or eliminating CO2 emissions. Given the urgency of the climate problem, we believe that an economic analysis, such as this is crucial to near-term CO2 emissions reductions.

Background Coronavirus disease 2019 (COVID-19) has left a significant impact on the world's health, economic and political systems; as of November 20, 2020, more than 57 million people have been infected worldwide, with over 1.3 million deaths. While the global spotlight is currently focused on combating this pandemic through means ranging from finding a treatment among existing therapeutic agents to inventing a vaccine that can aid in halting the further loss of life. Aim To collect all systematic reviews and meta-analyses published related to COVID-19 to better identify available evidence, highlight gaps in knowledge, and elucidate further meta-analyses and umbrella reviews that are yet to be performed. Methods We explored studies based on systematic reviews and meta-analyses with the key-terms, including severe acute respiratory syndrome (SARS), SARS virus, coronavirus disease, COVID-19, and SARS coronavirus-2. The included studies were extracted from Embase, Medline, and Cochrane databases. The publication timeframe of included studies ranged between January 01, 2020, to October 30, 2020. Studies that were published in languages other than English were not considered for this systematic review. The finalized full-text articles are freely accessible in the public domain. Results Searching Embase, Medline, and Cochrane databases resulted in 1906, 669, and 19 results, respectively, that comprised 2594 studies. 515 duplicates were subsequently removed, leaving 2079 studies. The inclusion criteria were systematic reviews or meta-analyses. 860 results were excluded for being a review article, scope review, rapid review, panel review, or guideline that produced a total of 1219 studies. After screening articles were categorized, the included articles were put into main groups of clinical presentation, epidemiology, screening and diagnosis, severity assessment, special populations, and treatment. Subsequently, there was a second subclassification into the following groups: gastrointestinal, cardiovascular, neurological, stroke, thrombosis, anosmia and dysgeusia, ocular manifestations, nephrology, cutaneous manifestations, D-dimer, lymphocyte, anticoagulation, antivirals, convalescent plasma, immunosuppressants, corticosteroids, hydroxychloroquine, renin-angiotensin-aldosterone system, technology, diabetes mellitus, obesity, pregnancy, children, mental health, smoking, cancer, and transplant. Conclusion Among the included articles, it is clear that further research is needed regarding treatment options and vaccines. With more studies, data will be less heterogeneous, and statistical analysis can be better applied to provide more robust clinical evidence. This study was not designed to give recommendations regarding the management of COVID-19.

We present the design and characterization of a 4-channel silicon photonics transmitter for 400Gbps DR4 data-center applications. A QSFP-DD transceiver module with this transmitter is demonstrated with reliable performance in real-time operation across 0~70 °C.

Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are common including cutaneous manifestations that either precede or follow manifestations of IBD. Cutaneous manifestations of IBD include erythema nodosum, pyoderma gangrenosum, oral lesions, and Sweet’s syndrome. Cutaneous manifestations of IBD tend to recur and extensive cases may require maintenance management with immunomodulators or biologics. However, the complications and adverse effects of long-term therapy with immunosuppressive agents are numerous and need to be considered before their initiation. We report a case of a Crohn’s disease patient with recurrent and debilitating cutaneous manifestation of lupus panniculitis that had sustained remission with hydroxychloroquine.

Speech-accompanying gestures constitute one information channel during communication. Some have argued that processing gestures engages the brain regions that support language comprehension. However, studies that have been used as evidence for shared mechanisms suffer from one or more of the following limitations: they (a) have not directly compared activations for gesture and language processing in the same study and relied on the fallacious reverse inference (Poldrack, 2006) for interpretation, (b) relied on traditional group analyses, which are bound to overestimate overlap (e.g., Nieto-Castanon and Fedorenko, 2012), (c) failed to directly compare the magnitudes of response (e.g., Chen et al., 2017), and (d) focused on gestures that may have activated the corresponding linguistic representations (e.g., "emblems"). To circumvent these limitations, we used fMRI to examine responses to gesture processing in language regions defined functionally in individual participants (e.g., Fedorenko et al., 2010), including directly comparing effect sizes, and covering a broad range of spontaneously generated co-speech gestures. Whenever speech was present, language regions responded robustly (and to a similar degree regardless of whether the video contained gestures or grooming movements). In contrast, and critically, responses in the language regions were low - at or slightly above the fixation baseline - when silent videos were processed (again, regardless of whether they contained gestures or grooming movements). Brain regions outside of the language network, including some in close proximity to its regions, differentiated between gestures and grooming movements, ruling out the possibility that the gesture/grooming manipulation was too subtle. Behavioral studies on the critical video materials further showed robust differentiation between the gesture and grooming conditions. In summary, contra prior claims, language-processing regions do not respond to co-speech gestures in the absence of speech, suggesting that these regions are selectively driven by linguistic input (e.g., Fedorenko et al., 2011). Although co-speech gestures are uncontroversially important in communication, they appear to be processed in brain regions distinct from those that support language comprehension, similar to other extra-linguistic communicative signals, like facial expressions and prosody.

The durability of concrete structures has long been a concern of many countries, especially in the island country of Singapore, where many structures are constructed along coastal areas. Currently, the durability of concrete under marine conditions can be enhanced by the addition of admixtures, and using high grade concrete. The FRP system has been proven to be one of the effective method to strengthen the concrete structure. The FRP system, which composed of the epoxy and glass fiber was evaluated according to various standard testing methods to get the basic technical information of the FRP system. Concrete columns of high aspect ratio with the size of 420mm x 115mm x 1500mm, 200mm x 200mm x 700mm and 200mm x 300mm x 700mm were wrapped with the FRP system with 3 horizontal wrapping and tested to verify the effectiveness of FPR wrapping. The theoretical calculation by computer model were also performed to estimate the strength gain for comparison with testing results. The results showed that the FRP wrapping for this type of columns can increase the ultimate strength by an average of 31.8%, with a minimum of 24.4% and a maximum of 37.5%.

Background and Purpose— The ASTRAL score was recently introduced as a prognostic tool for acute ischemic stroke. It predicts 3-month outcome reliably in both the derivation and the validation European cohorts. We aimed to validate the ASTRAL score in a Chinese stroke population and moreover to explore its prognostic value to predict 12-month outcome. Methods— We applied the ASTRAL score to acute ischemic stroke patients admitted to 132 study sites of the China National Stroke Registry. Unfavorable outcome was assessed as a modified Rankin Scale score >2 at 3 and 12 months. Areas under the curve were calculated to quantify the prognostic value. Calibration was assessed by comparing predicted and observed probability of unfavorable outcome using Pearson correlation coefficient. Results— Among 3755 patients, 1473 (39.7%) had 3-month unfavorable outcome. Areas under the curve for 3 and 12 months were 0.82 and 0.81, respectively. There was high correlation between observed and expected probability of unfavorable 3- and 12-month outcome (Pearson correlation coefficient: 0.964 and 0.963, respectively). Conclusions— ASTRAL score is a reliable tool to predict unfavorable outcome at 3 and 12 months after acute ischemic stroke in the Chinese population. It is a useful tool that can be readily applied in clinical practice to risk-stratify acute stroke patients.

A process-based model was used to simulate biomass production of Norway spruce under both current climate and climate change scenarios. The model was parameterized for Nordmoen in south-east Norway using real climate data for the period 1987-1989. The model was applied to predict the biomass production responses to three climate change scenarios. The results showed that net primary production (NPP) increased by 7% under an elevated annual mean air temperature of 4°C from the current 10.1 t dry mass ha -1 yr -1 . A doubled current ambient CO 2 concentration significantly increased NPP by 36%. The scenario of both elevated temperature and elevated CO 2 concentration led to an increase in the NPP of 49%, higher than the sum of the two effects acting singly. The results also showed that forest production responses to climate change depend on the conditions of climate used for reference.

Pts with hematologic malignancies (HM) are at high risk of developing SS and sepsis-related mortality. The diagnosis of sepsis requires suspicion of infection accompanied by at least two signs of systemic inflammation. The SIRS criteria were devised to improve the early bedside detection of sepsis and provide objective inclusion criteria for clinical research. Cut-point values based on consensus opinion are: HR >90, Temp > 100.4 or 20, and WBC >12k or Methods: The association between the SIRS and SS was evaluated in hospitalized adult pts (age 18–83) with HM in a prospective single-center, nested case-control study. The primary outcome was SS, defined as an infection resulting in cardiovascular or respiratory failure. Vital signs were performed every eight hours. Of the 547 pts who consented for the study, 54 developed SS (9.9% CI 7.7–12.7%). Using incidence density sampling, 211 controls were selected by matching on length of stay at time of SS. Evidence-based cut-points were then derived for the individual SIRS variables by examining risk estimates based on variable percentiles. Results: At hospital admission, HR, RR, BP, WBC, ANC, age, diagnosis, and transplant status were similar between the groups. In univariable analysis (24° prior to SS), significance of the four individual SIRS variables were: HR (p=.001), RR (p 20, OR 8.3, CI 2.8–24.4 p Conclusions: This study is the first to evaluate and define the test characteristics of the SIRS criteria in hospitalized pts with HM. The rationale for excluding HM patients from SS clinical trials based on diagnostic concerns should be revisited when planning future SS studies. Fever, tachycardia and tachypnea seem most predictive in this population. These results suggest that cut-points for significant SIRS variables can be redefined to improve the specificity of the SIRS score. Additional markers for the early detection of SS may further improve upon SIRS in HM pts. SIRS Score Sensitivity % (95 CI) Specificity LR(+) 1 98 (97–99) 12 (8–18) 1.1 2 76 (71–81) 60 (54–66) 1.9 3 39 (33–45) 91 (88–94) 4.3 4 7 (4–11) 99 (99–100) 15.6