Access to personalised dementia care planning in primary care: a mixed methods evaluation of the PriDem intervention.

OBJECTIVES: Provision of personalised care planning is a national priority for people with dementia. Research suggests a lack of quality and consistency of care plans and reviews. The PriDem model of care was developed to deliver feasible and acceptable primary care-based postdiagnostic dementia care. We aimed to increase the adoption of personalised care planning for people with dementia, exploring implementation facilitators and barriers. DESIGN: Mixed-method feasibility and implementation study. SETTING: Seven general practices from four primary care networks (PCNs) in the Northeast and Southeast of England. PARTICIPANTS: A medical records audit collected data on 179 community-dwelling people with dementia preintervention, and 215 during the intervention year. The qualitative study recruited 26 health and social care professionals, 14 people with dementia and 16 carers linked to participating practices. INTERVENTION: Clinical dementia leads (CDL) delivered a 12-month, systems-level intervention in participating PCNs, to develop care systems, build staff capacity and capability, and deliver tailored care and support to people with dementia and their carers. PRIMARY AND SECONDARY OUTCOME MEASURES: Adoption of personalised care planning was assessed through a preintervention and postintervention audit of medical records. Implementation barriers and facilitators were explored through semistructured qualitative interviews and non-participant observation, analysed using codebook thematic analysis informed by Normalisation Process Theory. RESULTS: The proportion of personalised care plans increased from 37.4% (95% CI 30.3% to 44.5%) preintervention to 64.7% (95% CI 58.3% to 71.0%) in the intervention year. Qualitative findings suggest that the flexible nature of the PriDem intervention enabled staff to overcome contextual barriers through harnessing the skills of the wider multidisciplinary team, delivering increasingly holistic care to patients. CONCLUSIONS: Meaningful personalised care planning can be achieved through a team-based approach. Although improved guidelines for care planning are required, commissioners should consider the benefits of a CDL-led approach. TRIAL REGISTRATION NUMBER: ISRCTN11677384.

Evaluating a model of best practice in primary care led post-diagnostic dementia care: feasibility and acceptability findings from the PriDem study.

OBJECTIVES: To evaluate the feasibility and acceptability of a primary care-based intervention for improving post-diagnostic dementia care and support (PriDem), and implementation study procedures. DESIGN: A non-randomised, mixed methods, feasibility study. SETTING: Seven general practices from four primary care networks (PCNs) in the Northeast and Southeast of England. PARTICIPANTS: We aimed to recruit 80 people with dementia (PWD) and 66 carers INTERVENTION: Clinical Dementia Leads delivered a 12-month intervention in participating PCNs, to develop care systems, build staff capacity and capability, and deliver tailored care and support to PWD and carers. OUTCOMES: Recruitment and retention rates were measured. A mixed methods process evaluation evaluated feasibility and acceptability of the intervention and study procedures. Using electronic care records, researchers extracted service use data and undertook a dementia care plan audit, preintervention and postintervention, assessing feasibility of measuring the primary implementation outcome: adoption of personalised care planning by participating general practices. Participants completed quality of life, and service use measures at baseline, 4 and 9 months. RESULTS: 60 PWD (75% of recruitment target) and 51 carers (77% of recruitment target) were recruited from seven general practices across four PCNs. Retention rate at 9 months was 70.0% of PWD and 76.5% of carers. The recruitment approach showed potential for including under-represented groups within dementia. Despite implementation challenges, the intervention was feasible and acceptable, and showed early signs of sustainability. Study procedures were feasible and accessible, although researcher capacity was crucial. Participants needed time and support to engage with the study. Care plan audit procedures were feasible and acceptable. CONCLUSIONS: The PriDem model is an acceptable and feasible intervention. A definitive study is warranted to fully inform dementia care policy and personalised dementia care planning guidance. Successful strategies to support inclusion of PWD and their carers in future research were developed. TRIAL REGISTRATION NUMBER: ISRCTN11677384.

Chronic use of Antihypertensive Medications and Peak Exercise Blood Pressure in Adult Men and Women from the BALL ST Cohort.

PURPOSE: To determine if individuals chronically (>1 year) prescribed antihypertensive medications have a normal BP response to peak exercise compared to unmedicated individuals. METHODS: Participants included 2,555 adults from the Ball State Adult Fitness Longitudinal Lifestyle STudy cohort who performed a peak treadmill exercise test. Participants were divided into groups by sex and antihypertensive medication status. Individuals prescribed antihypertensive medications for >1 year were included. Exaggerated and blunted SBP within each group was categorized using the Fitness Registry and the Importance of Exercise: A National Database (FRIEND) and absolute criteria as noted by the Amercian Heart Association. RESULTS: The unmedicated group had a greater prevalence (p < 0.05) of blunted SBP responses, whereas the medicated group had a higher prevalence (p < 0.05) of exaggerated SBP responses using both the FRIEND and absolute criteria. Peak SBP was higher (p < 0.01) in medicated compared to unmedicated participants in the overall cohort when controlling for age and sex, but not after controlling for resting SBP (p = 0.613), risk factors (p = 0.104), or cardiorespiratory fitness (p = 0.191). When men and women were assessed independently, peak SBP remained higher in the medicated women after controlling for age and resting SBP (p = 0.039), but not for men (p = 0.311). Individuals on beta-blockers had a higher peak SBP even after controlling for age, sex, risk factors and cardiorespiratory fitness (p = 0.022). CONCLUSIONS: Individuals on antihypertensive medications have a higher peak SBP response to exercise. Given the prognostic value of exaggerated peak SBP, control of exercise BP should be considered in routine BP assessment and in the treatment of hypertension.

Group B Streptococcus Brain Abscess in a Neonate with Bilateral Otorrhea.

Introduction Group B streptococcus (GBS) is the leading cause of bacterial sepsis and meningitis in neonates worldwide, but brain abscess secondary to GBS is extremely rare. While temporal brain abscesses have been described as a sequelae of otogenic infections in children and adults, such a presentation has not been described in neonates. Case Description An 8-day-old female infant presented with a fever and irritability along with bilateral purulent otorrhea. Maternal GBS screening was negative, but the delivery was complicated by chorioamnionitis. Workup revealed neutrophilic pleocytosis in the cerebrospinal fluid and culture of the ear drainage was positive for GBS. Magnetic resonance imaging showed a circular lesion with rim enhancement within the left temporal lobe concerning for an abscess. The infant was treated with 14 days of intravenous vancomycin, cefepime, and metronidazole followed by 10 weeks of intravenous ampicillin. The hospital course was complicated by seizures and obstructive hydrocephalus requiring multiple neurosurgical interventions. Conclusion Brain abscess can occur as a sequela of GBS meningitis in neonates, but they are rare. Otogenic infections require prompt evaluation and treatment as they can progress to serious central nervous infections in neonates.

Differential sex-dependent susceptibility to diastolic dysfunction and arrhythmia in cardiomyocytes from obese diabetic HFpEF model.

AIM: Sex-differences in heart failure with preserved ejection fraction (HFpEF) are important, but key mechanisms involved are incompletely understood. While animal models can inform about sex-dependent cellular and molecular changes, many previous preclinical HFpEF models have failed to recapitulate sex-dependent characteristics of human HFpEF. We tested for sex-differences in HFpEF using a two-hit mouse model (leptin receptor-deficient db/db mice plus aldosterone infusion for 4 weeks; db/db+Aldo). METHODS AND RESULTS: We performed echocardiography, electrophysiology, intracellular Ca2+ imaging, and protein analysis. Female HFpEF mice exhibited more severe diastolic dysfunction in line with increased titin N2B isoform expression and PEVK element phosphorylation, and reduced troponin-I phosphorylation. Female HFpEF mice had lower BNP levels than males despite similar comorbidity burden (obesity, diabetes) and cardiac hypertrophy in both sexes. Male HFpEF mice were more susceptible to cardiac alternans. Male HFpEF cardiomyocytes (versus female) exhibited higher diastolic [Ca2+], slower Ca2+ transient decay, reduced L-type Ca2+ current, more pronounced enhancement of the late Na+ current, and increased short-term variability of action potential duration (APD). However, male and female HFpEF myocytes showed similar downregulation of inward rectifier and transient outward K+ currents, APD prolongation, and frequency of delayed afterdepolarizations. Inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) reversed all pathological APD changes in HFpEF in both sexes, and empagliflozin pretreatment mimicked these effects of CaMKII inhibition. Vericiguat had only slight benefits, and these effects were larger in HFpEF females. CONCLUSION: We conclude that the db/db+Aldo preclinical HFpEF murine model recapitulates key sex-specific mechanisms in HFpEF and provides mechanistic insights into impaired excitation-contraction coupling and sex-dependent differential arrhythmia susceptibility in HFpEF with potential therapeutic implications. In male HFpEF myocytes, altered Ca2+ handling and electrophysiology aligned with diastolic dysfunction and arrhythmias, while worse diastolic dysfunction in females may depend more on altered myofilaments properties.

Using body-worn cameras in emergency departments: a pilot project.

Nurses and other emergency department (ED) staff often experience verbal and physical abuse as part of their everyday work. Body-worn cameras are one tool that ED staff can use to try to reduce workplace violence and abuse and have been shown to be effective in other healthcare environments, such as mental health units. This article describes a pilot service evaluation which used a survey to assess the effectiveness of using body-worn cameras for staff in the author's ED. Findings suggest that nurses believed the cameras provided support when they were confronted by abusive or aggressive patients or relatives and in some instances diffused potentially violent situations.

Protocol for the feasibility and implementation study of a model of best practice in primary care led postdiagnostic dementia care: PriDem.

INTRODUCTION: Care is often inadequate and poorly integrated after a dementia diagnosis. Research and policy highlight the unaffordability and unsustainability of specialist-led support, and instead suggest a task-shared model, led by primary care. This study is part of the PriDem primary care led postdiagnostic dementia care research programme and will assess delivery of an evidence-informed, primary care based, person-centred intervention. The intervention involves Clinical Dementia Leads (CDLs) working in primary care to develop effective dementia care systems that build workforce capacity and support teams to deliver tailored support to people living with dementia and their carers. METHODS AND ANALYSIS: This is a 15-month mixed-methods feasibility and implementation study, situated in four National Health Service (NHS) primary care networks in England. The primary outcome is adoption of personalised care planning by participating general practices, assessed through a patient records audit. Feasibility outcomes include recruitment and retention; appropriateness and acceptability of outcome measures; acceptability, feasibility and fidelity of intervention components. People living with dementia (n=80) and carers (n=66) will be recruited through participating general practices and will complete standardised measures of health and well-being. Participant service use data will be extracted from electronic medical records. A process evaluation will explore implementation barriers and facilitators through methods including semistructured interviews with people living with dementia, carers and professionals; observation of CDL engagement with practice staff; and a practice fidelity log. Process evaluation data will be analysed qualitatively using codebook thematic analysis, and quantitatively using descriptive statistics. Economic analysis will determine intervention cost-effectiveness. ETHICS AND DISSEMINATION: The study has received favourable ethical opinion from Wales REC4. NHS Confidentiality Advisory Group support allows researchers preconsent access to patient data. Results will inform intervention adaptations and a future large-scale evaluation. Dissemination through peer-review journals, engagement with policy-makers and conferences will inform recommendations for dementia services commissioning. TRIAL REGISTRATION NUMBER: ISRCTN11677384.

The Coronavirus Disease 2019 Rebound Study: A Prospective Cohort Study to Evaluate Viral and Symptom Rebound Differences in Participants Treated With Nirmatrelvir Plus Ritonavir Versus Untreated Controls.

BACKGROUND: The uptake of nirmatrelvir plus ritonavir (NPR) in patients with coronavirus disease 2019 (COVID-19) has been limited by concerns around the rebound phenomenon despite the scarcity of evidence around its epidemiology. The purpose of this study was to prospectively compare the epidemiology of rebound in NPR-treated and untreated participants with acute COVID-19 infection. METHODS: We designed a prospective, observational study in which participants who tested positive for COVID-19 and were clinically eligible for NPR were recruited to be evaluated for either viral or symptom clearance and rebound. Participants were assigned to the treatment or control group based on their decision to take NPR. Following initial diagnosis, both groups were provided 12 rapid antigen tests and asked to test on a regular schedule for 16 days and answer symptom surveys. Viral rebound based on test results and COVID-19 symptom rebound based on patient-reported symptoms were evaluated. RESULTS: Viral rebound incidence was 14.2% in the NPR treatment group (n = 127) and 9.3% in the control group (n = 43). Symptom rebound incidence was higher in the treatment group (18.9%) compared to controls (7.0%). There were no notable differences in viral rebound by age, gender, preexisting conditions, or major symptom groups during the acute phase or at the 1-month interval. CONCLUSIONS: This preliminary report suggests that rebound after clearance of test positivity or symptom resolution is higher than previously reported. However, notably we observed a similar rate of rebound in both the NPR treatment and control groups. Large studies with diverse participants and extended follow-up are needed to better understand the rebound phenomena.

Diabetes and Excess Aldosterone Promote Heart Failure With Preserved Ejection Fraction.

Background The pathobiology of heart failure with preserved ejection fraction (HFpEF) is still poorly understood, and effective therapies remain limited. Diabetes and mineralocorticoid excess are common and important pathophysiological factors that may synergistically promote HFpEF. The authors aimed to develop a novel animal model of HFpEF that recapitulates key aspects of the complex human phenotype with multiorgan impairments. Methods and Results The authors created a novel HFpEF model combining leptin receptor-deficient db/db mice with a 4-week period of aldosterone infusion. The HFpEF phenotype was assessed using morphometry, echocardiography, Ca2+ handling, and electrophysiology. The sodium-glucose cotransporter-2 inhibitor empagliflozin was then tested for reversing the arrhythmogenic cardiomyocyte phenotype. Continuous aldosterone infusion for 4 weeks in db/db mice induced marked diastolic dysfunction with preserved ejection fraction, cardiac hypertrophy, high levels of B-type natriuretic peptide, and significant extracardiac comorbidities (including severe obesity, diabetes with marked hyperglycemia, pulmonary edema, and vascular dysfunction). Aldosterone or db/db alone induced only a mild diastolic dysfunction without congestion. At the cellular level, cardiomyocyte hypertrophy, prolonged Ca2+ transient decay, and arrhythmogenic action potential remodeling (prolongation, increased short-term variability, delayed afterdepolarizations), and enhanced late Na+ current were observed in aldosterone-treated db/db mice. All of these arrhythmogenic changes were reversed by empagliflozin pretreatment of HFpEF cardiomyocytes. Conclusions The authors conclude that the db/db+aldosterone model may represent a distinct clinical subgroup of HFpEF that has marked hyperglycemia, obesity, and increased arrhythmia risk. This novel HFpEF model can be useful in future therapeutic testing and should provide unique opportunities to better understand disease pathobiology.

Regional connectivity drove bidirectional transmission of SARS-CoV-2 in the Middle East during travel restrictions.

Regional connectivity and land travel have been identified as important drivers of SARS-CoV-2 transmission. However, the generalizability of this finding is understudied outside of well-sampled, highly connected regions. In this study, we investigated the relative contributions of regional and intercontinental connectivity to the source-sink dynamics of SARS-CoV-2 for Jordan and the Middle East. By integrating genomic, epidemiological and travel data we show that the source of introductions into Jordan was dynamic across 2020, shifting from intercontinental seeding in the early pandemic to more regional seeding for the travel restrictions period. We show that land travel, particularly freight transport, drove introduction risk during the travel restrictions period. High regional connectivity and land travel also drove Jordan's export risk. Our findings emphasize regional connectedness and land travel as drivers of transmission in the Middle East.

Impact of polygenic risk communication: an observational mobile application-based coronary artery disease study.

We developed a smartphone application, MyGeneRank, to conduct a prospective observational cohort study (NCT03277365) involving the automated generation, communication, and electronic capture of response to a polygenic risk score (PRS) for coronary artery disease (CAD). Adults with a smartphone and an existing 23andMe genetic profiling self-referred to the study. We evaluated self-reported actions taken in response to personal CAD PRS information, with special interest in the initiation of lipid-lowering therapy. 19% (721/3,800) of participants provided complete responses for baseline and follow-up use of lipid-lowering therapy. 20% (n = 19/95) of high CAD PRS vs 7.9% (n = 8/101) of low CAD PRS participants initiated lipid-lowering therapy at follow-up (p-value = 0.002). Both the initiation of statin and non-statin lipid-lowering therapy was associated with degree of CAD PRS: 15.2% (n = 14/92) vs 6.0% (n = 6/100) for statins (p-value = 0.018) and 6.8% (n = 8/118) vs 1.6% (n = 2/123) for non-statins (p-value = 0.022) in high vs low CAD PRS, respectively. High CAD PRS was also associated with earlier initiation of lipid lowering therapy (average age of 52 vs 65 years in high vs low CAD PRS respectively, p-value = 0.007). Overall, degree of CAD PRS was associated with use of any lipid-lowering therapy at follow-up: 42.4% (n = 56/132) vs 28.5% (n = 37/130) (p-value = 0.009). We find that digital communication of personal CAD PRS information is associated with increased and earlier lipid-lowering initiation in individuals of high CAD PRS. Loss to follow-up is the primary limitation of this study. Alternative communication routes, and long-term studies with EHR-based outcomes are needed to understand the generalizability and durability of this finding.

Wintertime haze and ozone at Dinosaur National Monument.

Dinosaur National Monument (DINO) is located near the northeastern edge of the Uinta Basin and often experiences elevated levels of wintertime ground-level ozone. Previous studies have shown that high ozone mixing ratios in the Uinta Basin are driven by elevated levels of volatile organic compounds (VOCs) and nitrogen oxides (NOx) from regional oil and gas development coupled with temperature inversions and enhanced photochemistry from persistent snow cover. Here, we show that persistent snow cover and temperature inversions, along with abundant ammonia, also lead to wintertime haze in this region. A study was conducted at DINO from November 2018 through May 2020 where ozone, speciated fine and coarse aerosols, inorganic gases, and VOCs were measured. Three National Ambient Air Quality Standards (NAAQS) ozone exceedances were observed in the first winter, and no exceedances were observed in the second winter. In contrast, elevated levels of particulate matter were observed both winters, with 24-h averaged particle light extinction exceeding 100 Mm-1. These haze events were dominated by ammonium nitrate, and particulate organics were highly correlated with ammonium nitrate. Ammonium nitrate formation was limited by nitric acid in winter. As such, reductions in regional NOx emissions should reduce haze levels and improve visibility at DINO in winter. Long-term measurements of particulate matter from nearby Vernal, Utah, suggest that visibility impairment is a persistent issue in the Uinta Basin in winter. From April through October 2019, relatively clean conditions occurred, with average particle extinction of ~10 Mm-1. During this period, ammonium nitrate concentrations were lower by more than an order of magnitude, and contributions from coarse mass and soil to haze levels increased. VOC markers indicated that the high levels of observed pollutants in winter were likely from local sources related to oil and gas extraction activities.Implications: Elevated ground-level ozone and haze levels were observed at Dinosaur National Monument in winter. Haze episodes were dominated by ammonium nitrate, with 24-h averaged particle light extinction exceeding 100 Mm-1, reducing visual range near the surface to ~35 km. Despite elevated ammonium nitrate concentrations, additional gas-phase ammonia was available, such that any increase in NOx emissions in the region is likely to lead to even greater haze levels.

Emergence of an early SARS-CoV-2 epidemic in the United States.

The emergence of the COVID-19 epidemic in the United States (U.S.) went largely undetected due to inadequate testing. New Orleans experienced one of the earliest and fastest accelerating outbreaks, coinciding with Mardi Gras. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana had limited diversity compared to other U.S. states and that one introduction of SARS-CoV-2 led to almost all of the early transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras, and the festival dramatically accelerated transmission. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate epidemics.

Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Emergence of an early SARS-CoV-2 epidemic in the United States.

The emergence of the early COVID-19 epidemic in the United States (U.S.) went largely undetected, due to a lack of adequate testing and mitigation efforts. The city of New Orleans, Louisiana experienced one of the earliest and fastest accelerating outbreaks, coinciding with the annual Mardi Gras festival, which went ahead without precautions. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large, crowded events may have accelerated early transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana initially had limited sequence diversity compared to other U.S. states, and that one successful introduction of SARS-CoV-2 led to almost all of the early SARS-CoV-2 transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras and that the festival dramatically accelerated transmission, eventually leading to secondary localized COVID-19 epidemics throughout the Southern U.S.. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate COVID-19 epidemics on a local and regional scale.

A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage.

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.

Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, with >365,000 cases in California as of 17 July 2020. We investigated the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning nine counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least seven different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington state, with lack of a predominant lineage and limited transmission among communities. Lineages associated with outbreak clusters in two counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain the spread of SARS-CoV-2 in California and other states.

Selectively reduced contrast sensitivity in high schizotypy.

Deficits in the ability to encode small differences in contrast between adjacent parts of an image (contrast sensitivity) are well documented in schizophrenic patients. In the present study, we sought to determine whether contrast sensitivity deficits reported in schizophrenic patients are also evident in those who exhibit high schizotypy scores in a typical (i.e., non-schizophrenic) population. Using the O-Life Questionnaire, we determined the effects of schizotypy on spatial (0.5, 2 and 8 c/deg) and spatiotemporal (0.5 and 8 c/deg at 0.5 and 8 Hz) contrast sensitivity in 73 young (18-26 years), majority female (n = 68) participants. We found differences in contrast sensitivity that were spatial, spatiotemporal and O-Life subscale specific. Spatial contrast sensitivity was significantly lower in high, compared to low schizotypes at low spatial frequencies (0.5 c/deg) in those who scored highly on the Unusual Experiences and Cognitive Disorganisation O-Life subscales. For moving stimuli, individuals with high scores on the Unusual Experiences subscale exhibited lower spatiotemporal contrast sensitivity for 0.5 and 8 c/deg patterns drifting at 8 Hz. Although the effects reported here were relatively small, this is the first report of reduced contrast sensitivity in schizotypy.

Re-analysis of whole-exome sequencing data uncovers novel diagnostic variants and improves molecular diagnostic yields for sudden death and idiopathic diseases.

BACKGROUND: Whole-exome sequencing (WES) has become an efficient diagnostic test for patients with likely monogenic conditions such as rare idiopathic diseases or sudden unexplained death. Yet, many cases remain undiagnosed. Here, we report the added diagnostic yield achieved for 101 WES cases re-analyzed 1 to 7 years after initial analysis. METHODS: Of the 101 WES cases, 51 were rare idiopathic disease cases and 50 were postmortem "molecular autopsy" cases of early sudden unexplained death. Variants considered for reporting were prioritized and classified into three groups: (1) diagnostic variants, pathogenic and likely pathogenic variants in genes known to cause the phenotype of interest; (2) possibly diagnostic variants, possibly pathogenic variants in genes known to cause the phenotype of interest or pathogenic variants in genes possibly causing the phenotype of interest; and (3) variants of uncertain diagnostic significance, potentially deleterious variants in genes possibly causing the phenotype of interest. RESULTS: Initial analysis revealed diagnostic variants in 13 rare disease cases (25.4%) and 5 sudden death cases (10%). Re-analysis resulted in the identification of additional diagnostic variants in 3 rare disease cases (5.9%) and 1 sudden unexplained death case (2%), which increased our molecular diagnostic yield to 31.4% and 12%, respectively. CONCLUSIONS: The basis of new findings ranged from improvement in variant classification tools, updated genetic databases, and updated clinical phenotypes. Our findings highlight the potential for re-analysis to reveal diagnostic variants in cases that remain undiagnosed after initial WES.