Comparison between endovascular and surgical treatment of spinal dural arteriovenous fistulas: a single-center cohort and systematic review.

OBJECTIVE: With recent advancements in minimally invasive techniques, endovascular embolization has gained popularity as a first-line treatment option for spinal dural arteriovenous fistulas (sDAVFs). The authors present their institution's case series of sDAVFs treated endovascularly and surgically, and they performed a systemic review to assess the outcomes of both modalities of treatment. METHODS: The authors conducted a retrospective observational study of 24 consecutive patients with sDAVFs treated between 2013 and 2023. The primary outcome was the rate of occlusion, which was compared between the surgically and endovascularly treated sDAVFs. They also conducted a systemic review of all the literature comparing outcomes of endovascular and surgical treatment of sDAVFs. RESULTS: A total of 24 patients with 24 sDAVFs were studied. The mean patient age was 63.8 ± 15.5 years, and the majority of patients were male (n = 19, 79.2%). Of the 24 patients, 8 (33.3%) received endovascular treatment, 15 (62.5%) received surgical treatment, and 1 (4.2%) patient received both. Complete occlusion at first follow-up was higher in the surgical cohort but did not achieve statistical significance (66.7% vs 25%, p = 0.52). Recurrence was higher in the endovascular cohort (37.5% vs 13.3%, p = 0.3), while the rate of postprocedural complications was higher in the surgical cohort (13.3% vs 0%, p = 0.52); however, neither of these differences was statistically significant. CONCLUSIONS: Endovascular embolization in the management of sDAVFs is an alternative treatment to surgery, whose long-term efficacy is still under investigation. These findings suggest overall comparable outcomes between endovascular and open surgical treatment of sDAVFs. Future studies are needed to determine the role of endovascular embolization in the overall management of sDAVFs.

The effects of selected sedatives on basal and stimulated serum cortisol concentrations in healthy dogs.

Background: Hormone assessment is typically recommended for awake, unsedated dogs. However, one of the most commonly asked questions from veterinary practitioners to the endocrinology laboratory is how sedation impacts cortisol concentrations and the adrenocorticotropic hormone (ACTH) stimulation test. Butorphanol, dexmedetomidine, and trazodone are common sedatives for dogs, but their impact on the hypothalamic-pituitary-adrenal axis (HPA) is unknown. The objective of this study was to evaluate the effects of butorphanol, dexmedetomidine, and trazodone on serum cortisol concentrations. Methods: Twelve healthy beagles were included in a prospective, randomized, four-period crossover design study with a 7-day washout. ACTH stimulation test results were determined after saline (0.5 mL IV), butorphanol (0.3 mg/kg IV), dexmedetomidine (4 µg/kg IV), and trazodone (3-5 mg/kg PO) administration. Results: Compared to saline, butorphanol increased basal (median 11.75 µg/dL (range 2.50-23.00) (324.13 nmol/L; range 68.97-634.48) vs 1.27 µg/dL (0.74-2.10) (35.03 nmol/L; 20.41-57.93); P < 0.0001) and post-ACTH cortisol concentrations (17.05 µg/dL (12.40-26.00) (470.34 nmol/L; 342.07-717.24) vs 13.75 µg/dL (10.00-18.90) (379.31 nmol/L; 275.96-521.38); P ≤ 0.0001). Dexmedetomidine and trazodone did not significantly affect basal (1.55 µg/dL (range 0.75-1.55) (42.76 nmol/L; 20.69-42.76); P = 0.33 and 0.79 µg/dL (range 0.69-1.89) (21.79 nmol/L; 19.03-52.14); P = 0.13, respectively, vs saline 1.27 (0.74-2.10) (35.03 nmol/L; 20.41-57.93)) or post-ACTH cortisol concentrations (14.35 µg/dL (range 10.70-18.00) (395.86 nmol/L; 295.17-496.55); (P = 0.98 and 12.90 µg/dL (range 8.94-17.40) (355.86 nmol/L; 246.62-480); P = 0.65), respectively, vs saline 13.75 µg/dL (10.00-18.60) (379.31 nmol/L; 275.86-513.10). Conclusion: Butorphanol administration should be avoided prior to ACTH stimulation testing in dogs. Further evaluation of dexmedetomidine and trazodone's effects on adrenocortical hormone testing in dogs suspected of HPA derangements is warranted to confirm they do not impact clinical diagnosis.

Evolutionary perspectives on substance and behavioural addictions: Distinct and shared pathways to understanding, prediction and prevention.

Addiction poses significant social, health, and criminal issues. Its moderate heritability and early-life impact, affecting reproductive success, poses an evolutionary paradox: why are humans predisposed to addictive behaviours? This paper reviews biological and psychological mechanisms of substance and behavioural addictions, exploring evolutionary explanations for the origin and function of relevant systems. Ancestrally, addiction-related systems promoted fitness through reward-seeking, and possibly self-medication. Today, psychoactive substances disrupt these systems, leading individuals to neglect essential life goals for immediate satisfaction. Behavioural addictions (e.g. video games, social media) often emulate ancestrally beneficial behaviours, making them appealing yet often irrelevant to contemporary success. Evolutionary insights have implications for how addiction is criminalised and stigmatised, propose novel avenues for interventions, anticipate new sources of addiction from emerging technologies such as AI. The emerging potential of glucagon-like peptide 1 (GLP-1) agonists targeting obesity suggest the satiation system may be a natural counter to overactivation of the reward system.

Changing perspectives on autism: Overlapping contributions of evolutionary psychiatry and the neurodiversity movement.

Perspectives on autism and psychiatric conditions are affected by a mix of scientific and social influences. Evolutionary psychiatry (EP) and the neurodiversity movement are emerging paradigms that reflect these distinct influences, with the former grounded in scientific theory and the latter driven by political and social principles. Despite their separate foundations, there is a significant overlap between EP and neurodiversity that has not been explored. Specifically, both paradigms reframe disorders as natural cognitive differences rather than disease; expand the concept of "normal" beyond that implied in modern psychiatry; focus on relative strengths; recognize that modern environments disadvantage certain individuals to cause functional impairment; emphasize cognitive variation being socially accommodated and integrated rather than treated or cured; and can help reduce stigmatization. However, in other ways, they are distinct and sometimes in conflict. EP emphasizes scientific explanation, defines "dysfunction" in objective terms, and differentiates heterogenous cases based on underlying causes (e.g. autism due to de novo genetic mutations). The neurodiversity movement emphasizes social action, removes barriers to inclusion, promotes inclusive language, and allows unrestricted identification as neurodivergent. By comparing and contrasting these two approaches, we find that EP can, to some extent, support the goals of neurodiversity. In particular, EP perspectives could be convincing to groups more responsive to scientific evidence and help achieve a middle ground between neurodiversity advocates and critics of the movement.

Causes and Predictors of 30-Day Readmission in Patients With Stroke Undergoing Mechanical Thrombectomy: A Large Single-Center Experience.

BACKGROUND AND OBJECTIVES: The 30-day readmission rate has emerged as a metric of quality care and is associated with increased health care expenditure. We aim to identify the rate and causes of 30-day readmission after mechanical thrombectomy and provide the risk factors of readmission to highlight high-risk patients who may require closer care. METHODS: This is a retrospective study from a prospectively maintained database of 703 patients presenting for mechanical thrombectomy between 2017 and 2023. All patients who presented with a stroke and underwent a mechanical thrombectomy were included in this study. Patients who were deceased on discharge were excluded from this study. RESULTS: Our study comprised 703 patients, mostly female (n = 402, 57.2%) with a mean age of 70.2 years ±15.4. The most common causes of readmission were cerebrovascular events (stroke [n = 21, 36.2%], intracranial hemorrhage [n = 9, 15.5%], and transient ischemic attack [n = 1, 1.7%]).Other causes of readmission included cardiovascular events (cardiac arrest [n = 4, 6.9%] and bradycardia [n = 1, 1.7%]), infection (wound infection postcraniectomy [n = 3, 5.2%], and pneumonia [n = 1, 1.7%]). On multivariate analysis, independent predictors of 30-day readmission were history of smoking (odds ratio [OR]: 2.2, 95% CI: 1.1-4.2) P = .01), distal embolization (OR: 3.2, 95% CI: 1.1-8.7, P = .03), decompressive hemicraniectomy (OR: 9.3, 95% CI: 3.2-27.6, P < .01), and intracranial stent placement (OR: 4.6, 95% CI: 2.4-8.7) P < .01). CONCLUSION: In our study, the rate of 30-day readmission was 8.3%, and the most common cause of readmission was recurrent strokes. We identified a history of smoking, distal embolization, decompressive hemicraniectomy, and intracranial stenting as independent predictors of 30-day readmission in patients with stroke undergoing mechanical thrombectomy.

Transradial versus transfemoral access routes for diagnostic cerebral angiography: a large single-center comparative cost-analysis study.

OBJECTIVE: Recently, the transradial (TR) approach has become a common alternative because of its safety profile and increased patient satisfaction compared with the transfemoral (TF) route. Both routes are associated with their respective associated costs, and differences typically emerge on the basis of patient anatomy, operator expertise, and occurrence of complications. The authors' objective was to compare the overall costs of diagnostic cerebral angiography via both routes and to shed light on the individual equipment costs of each route. METHODS: This retrospective single-center study of 926 elective diagnostic angiograms was performed between December 2019 and March 2022. RESULTS: The study comprised of 314 and 612 angiograms performed through the TF and TR routes, respectively. A significantly greater proportion of female patients were included in the TF cohort (79.3% vs 67.8%, p < 0.001), and most other demographic characteristics and baseline modified Rankin Scale scores were comparable between cohorts. The overall cost of patients utilizing the TR route was comparable to that of the TF route (mean ± SD $12,591.80 ± $19,128.00 vs $12,789.50 ± 18,424.00, p = 0.88). However, the median cost of catheters was significantly higher in TR group ($55.20 vs $12.40, p = 0.03), while the median costs of closure devices ($87.00 vs $20.20 p < 0.001) and sheaths ($44.60 ± 11.3 vs $41.10 ± 3.10, p < 0.001) were significantly higher in the TF group. CONCLUSIONS: Overall, the authors' study showed that the TR approach can be a less expensive option for patients undergoing diagnostic cerebral angiography, especially if complications occur. Future studies may corroborate these findings and potentially lead to the adoption of TR as a low-cost, efficient, gold-standard technique for cerebral angiography.

The Rate and Predictors of 30-Day Readmission in Patients Treated for Unruptured Cerebral Aneurysms: A Large Single-Center Study.

BACKGROUND AND OBJECTIVES: Numerous studies of various populations and diseases have shown that unplanned 30-day readmission rates are positively correlated with increased morbidity and all-cause mortality. In this study, we aim to provide the rate and predictors of 30-day readmission in patients undergoing treatment for unruptured intracranial aneurysms. METHODS: This is a retrospective study of 525 patients presenting for aneurysm treatment between 2017 and 2022. All patients who were admitted and underwent a successful treatment of their unruptured intracerebral aneurysms were included in the study. The primary outcome was the rate and predictors of 30-day readmission. RESULTS: The rate of 30-day readmission was 6.3%, and the mean duration to readmission was 7.8 days ± 6.9. On univariate analysis, factors associated with 30-day readmission were antiplatelet use on admission (odds ratio [OR]: 0.4, P = .009), peri-procedural rupture (OR: 15.8, P = .007), surgical treatment of aneurysms (OR: 2.2, P = .035), disposition to rehabilitation (OR: 9.5, P < .001), and increasing length of stay (OR: 1.1, P = .0008). On multivariate analysis, antiplatelet use on admission was inversely correlated with readmission (OR: 0.4, P = .045), whereas peri-procedural rupture (OR: 9.5, P = .04) and discharge to rehabilitation (OR: 4.5, P = .029) were independent predictors of 30-day readmission. CONCLUSION: In our study, risk factors for 30-day readmission were aneurysm rupture during the hospital stay and disposition to rehabilitation, whereas the use of antiplatelet on admission was inversely correlated with 30-day readmission. Although aneurysm rupture is a nonmodifiable risk factor, more studies are encouraged to focus on the correlation of antiplatelet use and rehabilitation disposition with 30-day readmission rates.

Predictors of Transfemoral Access Site Complications in Neuroendovascular Procedures: A large Single-Center Cohort Study.

OBJECTIVE: The transfemoral (TF) route has historically been the preferred access site for endovascular procedures. However, despite its widespread use, TF procedures may confer morbidity as a result of access site complications. The aim of this study is to provide the rate and predictors of TF access site complications for neuroendovascular procedures. METHODS: This is a single center retrospective study of TF neuroendovascular procedures performed between 2017 and 2022. The incidence of complications and associated risk factors were analyzed across a large cohort of patients. RESULTS: The study comprised of 2043 patients undergoing transfemoral neuroendovascular procedures. The composite rate of access site complications was 8.6 % (n = 176). These complications were divided into groin hematoma formation (n = 118, 5.78 %), retroperitoneal hematoma (n = 14, 0.69 %), pseudoaneurysm formation (n = 40, 1.96 %), and femoral artery occlusion (n = 4, 0.19 %). The cross-over to trans radial access rate was 1.1 % (n = 22). On univariate analysis, increasing age (OR=1.0, p = 0.06) coronary artery disease (OR=1.7, p = 0.05) peripheral vascular disease (OR=1.9, p = 0.07), emergent mechanical thrombectomy procedures (OR=2.1, p < 0.001) and increasing sheath size (OR=1.3, p < 0.001) were associated with higher TF access site complications. On multivariate analysis, larger sheath size was an independent risk factor for TF access site complications (OR=1.8, p = 0.02). CONCLUSION: Several pertinent factors contribute towards the incidence of TF access site complications. Factors associated with TF access site complications include patient demographics (older age) and clinical risk factors (vascular disease), as well as periprocedural factors (sheath size).

Intra- and interindividual reliability of muscle pain induced by an intramuscular injection of hypertonic saline injection into the quadriceps.

BACKGROUND: Intramuscular injections of hypertonic saline are commonly used to induce experimental muscle pain, but reliability data on this technique are lacking. This study investigated the intra- and interindividual reliability of pain measures from a hypertonic saline injection into the vastus lateralis. METHODS: Fourteen healthy participants (6 female) attended three laboratory visits where they received an intramuscular injection of 1 mL hypertonic saline into the vastus lateralis. Changes in pain intensity were recorded on an electronic visual analogue scale, and pain quality was assessed after pain had resolved. Reliability was assessed with the coefficient of variation (CV), minimum detectable change (MDC) and intraclass correlation coefficient (ICC) with 95% CIs. RESULTS: Mean pain intensity displayed high levels of intraindividual variability (CV = 16.3 [10.5-22.0]%) and 'poor' to 'very good' relative reliability (ICC = 0.71 [0.45-0.88]) but had a MDC of 11 [8-16] au (out of 100). Peak pain intensity exhibited high levels of intraindividual variability (CV = 14.8 [8.8-20.8]%) with 'moderate' to 'excellent' levels of relative reliability (ICC = 0.81 [0.62-0.92]), whereas the MDC was 18 [14-26] au. Measures of pain quality exhibited good reliability. Interindividual variability in pain measures was high (CV > 37%). CONCLUSIONS: Intramuscular injections of 1 mL of hypertonic saline into the vastus lateralis display substantial levels of interindividual variability, but MDC is below the clinically important changes in pain. This model of experimental pain is suitable for studies involving repeated exposures. SIGNIFICANCE: Many pain research studies have performed intramuscular injections of hypertonic saline to investigate responses to muscle pain. However, the reliability of this technique is not well established. We examined the pain response over three repeated sessions of a hypertonic saline injection. The pain induced by hypertonic saline has considerable interindividual variability but has largely acceptable intraindividual reliability. Therefore, the injections of hypertonic saline to induce muscle pain are a reliable model of experimental muscle pain.

Safety of Mechanical Thrombectomy in Patients on Antiplatelet/Anticoagulation.

BACKGROUND: Mechanical thrombectomy (MT) is performed in patients who are already on anticoagulation (AC)/antiplatelet therapy (AP). However, data are insufficient regarding MT's safety and efficacy profiles in these patients. OBJECTIVE: Investigate the outcome of stroke patients already on anticoagulation/antiplatelet receiving MT. METHODS: We included consecutive acute ischemic stroke patients treated with MT for 10 years (2012-2022) in a comprehensive stroke center. Baseline variables, efficacy (recanalization [Thrombolysis in Cerebral Infraction] ≥ 2b), good functional outcome (modified Ranking Scale ≤ 2 at 3 months), and safety (symptomatic intracranial hemorrhage [sICH], mortality rates) were evaluated. Additionally, we conducted a subgroup analysis of patients with prior single-AP versus DAPT. RESULTS: Six hundred forty-six patients were included (54.5% women, median age 71 years), 84 (13%) were on AC, 196 (30.3%) on AP, and 366 (56.7%) in the control group. The AC and AP groups were older and had more comorbidities. sICH occurred in 7.3% of cases. There was no significant difference in sICH incidence across the groups. The AC group had a lower rate of intravenous thrombolysis (15.9%; P < 0.001), a higher rate of sICH (11.9% vs. AP 7.7% and control 6%; P = 0.172), and higher mortality at discharge (17.9% vs. AP 8.7% and control 10.4%; P = 0.07). However, the groups had similar functional outcomes and mortality rates at 3 months. Successful recanalization was achieved in 92.7% and was similar across groups. Multivariable logistic regression and the subgroup analysis (single-AP vs. dual AP) did not reveal statistically significant associations. CONCLUSIONS: MT in patients with prior anticoagulation and AP presenting with acute ischemic strokeis feasible, effective, and safe.

A Comparison of Outcomes Between Transfemoral Versus Transradial Access for Carotid Stenting.

BACKGROUND: The transradial (TR) approach has emerged as an alternative to the transfemoral (TF) approach in carotid artery stenting (CAS) because of its perceived benefits in access site complications and overall patient experience. OBJECTIVE: To assess outcomes of TF vs TR approach for CAS. METHODS: This is a retrospective single-center review of patients receiving CAS through the TR or TF route between 2017 and 2022. All patients with symptomatic and asymptomatic carotid disease who underwent attempted CAS were included in our study. RESULTS: A total of 342 patients were included in this study: 232 underwent CAS through TF approach vs 110 through the TR route. On univariate analysis, the rate of overall complications was more than double for the TF vs TR cohort; however, this did not achieve statistical significance (6.5% vs 2.7%, odds ratio [OR] = 0.59 P = .36). The rate of cross-over from TR to TF was significantly higher on univariate analysis (14.6 % vs 2.6%, OR = 4.77, P = .005) and on inverse probability treatment weighting analysis (OR = 6.11, P < .001). The rate of in-stent stenosis (TR: 3.6% vs TF: 2.2%, OR = 1.71, P = .43) and strokes at follow-up (TF: 2.2% vs TR: 1.8%, OR = 0.84, P = .84) was not significantly different. Finally, median length of stay was comparable between both cohorts. CONCLUSION: The TR approach is safe, feasible, and provides similar rates of complications and high rates of successful stent deployment compared with the TF route. Neurointerventionalists adopting the radial first approach should carefully assess the preprocedural computed tomography angiography to identify patients amenable to TR approach for carotid stenting.

Evobiopsychosocial medicine.

The biopsychosocial model remains the de facto framework of current healthcare, but lacks causational depth, scientific rigour, or any recognition of the importance of evolutionary theory for understanding health and disease. In this article it is updated to integrate Tinbergen's four questions with the three biopsychosocial levels. This 'evobiopsychosocial' schema provides a more complete framework for understanding causation of medical conditions. Its application is exemplified by tabulating depression, rheumatoid arthritis and COVID-19 within its format, which highlights the direct research and practical applications uniquely offered by evolutionary medicine. An evobiopsychosocial framework can serve as a useful tool to introduce evolutionary concepts into mainstream medicine by highlighting the broad and specific contributions of evolutionary analysis to researching, treating and preventing health conditions, providing a suitable next step for the mainstream model of medicine.

The Effect of COVID-19 Vaccines on Stroke Outcomes: A Single-Center Study.

BACKGROUND: One of the defining narratives of the COVID-19 pandemic has been the acceptance and distribution of vaccine. To compare the outcomes of COVID-19 positive vaccinated and unvaccinated stroke patients. METHODS: This is a single-center retrospective study of COVID-19-vaccinated and unvaccinated stroke patients between April 2020 and March 2022. All patients presenting with stroke regardless of treatment modalities were included. National Institutes of Health Stroke Scale was used to assess stroke severity. The primary outcome was functional capacity of the patients at discharge. RESULTS: The study cohort comprised 203 COVID-19 positive stroke patients divided into 139 unvaccinated and 64 fully vaccinated patients. At discharge, the modified Rankin scale score was significantly lower in the vaccinated cohort (3[1-4] vs. 4[2-5], odds ratio = 0.508, P = 0.011). At 3 months of follow-up, the median modified Rankin scale score was comparable between both cohorts. CONCLUSIONS: Although vaccination did not show any significant difference in stroke patient outcomes on follow-up, vaccines were associated with lower rates of morbidity and mortality at discharge among stroke patients during the pandemic.

Comparison of Flow-Redirection Endoluminal Device and Pipeline Embolization Device in the Treatment of Intracerebral Aneurysms.

BACKGROUND: The use of flow diverters for treating intracranial aneurysms has been widely used in the past decade; however, data comparing pipeline embolization device (PED; Medtronic Inc) and flow-redirection endoluminal device (FRED; MicroVention) in the treatment of intracranial aneurysms remain scarce. OBJECTIVE: To compare the outcomes of PED and FRED in the treatment of intracranial aneurysms. METHODS: This is a single-center retrospective review of aneurysms treated with PED and FRED devices. Patients treated with PED or FRED were included. Cases requiring multiple or adjunctive devices were excluded. Primary outcome was complete aneurysm occlusion at 6 months. Secondary outcomes included good functional outcome, need for retreatment, and any complication. RESULTS: The study cohort comprised 150 patients, including 35 aneurysms treated with FRED and 115 treated with PED. Aneurysm characteristics including location and size were comparable between the 2 cohorts. 6-month complete occlusion rate was significantly higher in the PED cohort (74.7% vs 51.5%; P = .017) but lost significance after inverse probability weights. Patients in the PED cohort were associated with higher rates of periprocedural complications (3.5% vs 0%; P = .573), and the rate of in-stent stenosis was approximately double in the FRED cohort (15.2% vs 6.9%; P = .172). CONCLUSION: Compared with PED, FRED offers modest 6-month occlusion rates, which may be due to aneurysmal and baseline patient characteristics differences between both cohorts. Although not significant, FRED was associated with a higher complication rate mostly because of in-stent stenosis. Additional studies with longer follow-up durations should be conducted to further evaluate FRED thrombogenicity.

Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa.

Background: More than half the global population has been exposed to SARS-CoV-2. Naturally induced immunity influences the outcome of subsequent exposure to variants and vaccine responses. We measured anti-spike IgG responses to explore the basis for this enhanced immunity. Methods: A prospective cohort study of mothers in a South African community through ancestral/beta/delta/omicron SARS-CoV-2 waves (March 2020-February 2022). Health seeking behaviour/illness were recorded and post-wave serum samples probed for IgG to Spike (CoV2-S-IgG) by ECLISA. To estimate protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter for unvaccinated and vaccinated adults. Findings: Despite little disease, 176/339 (51·9%) participants were seropositive following wave 1, rising to 74%, 89·8% and 97·3% after waves 2, 3 and 4 respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection with the greatest protection for beta and least for omicron. Vaccination induced higher CoV2-S-IgG in seropositive compared to naïve vaccinees. Amongst seropositive participants, proportions above the 50% protection against infection threshold were 69% (95% CrI: 62, 72) following 1 vaccine dose, 63% (95% CrI: 63, 75) following 2 doses and only 11% (95% CrI: 7, 14) in unvaccinated during the omicron wave. Interpretation: Naturally induced CoV2-S-IgG do not achieve high enough levels to prevent omicron infection in most exposed individuals but are substantially boosted by vaccination leading to significant protection. A single vaccination in those with prior immunity is more immunogenic than 2 doses in a naïve vaccinee and may provide adequate protection. Funding: UK NIH GECO award (GEC111), Wellcome Trust Centre for Infectious Disease Research in Africa (CIDRI), Bill & Melinda Gates Foundation, USA (OPP1017641, OPP1017579) and NIH H3 Africa (U54HG009824, U01AI110466]. HZ is supported by the SA-MRC. MPN is supported by an Australian National Health and Medical Research Council Investigator Grant (APP1174455). BJQ is supported by a grant from the Bill and Melinda Gates Foundation (OPP1139859). Stefan Flasche is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant number 208812/Z/17/Z).

High Neutralizing Antibody Levels Against Severe Acute Respiratory Syndrome Coronavirus 2 Omicron BA.1 and BA.2 After UB-612 Vaccine Booster.

The highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has caused high rates of breakthrough infections in those previously vaccinated with ancestral strain coronavirus disease 2019 (COVID-19) vaccines. Here, we demonstrate that a booster dose of UB-612 vaccine candidate delivered 7-9 months after primary vaccination increased neutralizing antibody levels by 131-, 61-, and 49-fold against ancestral SARS-CoV-2 and the Omicron BA.1 and BA.2 variants, respectively. Based on the receptor-binding domain protein binding antibody responses, the UB-612 third-dose booster may lead to an estimated approximately 95% efficacy against symptomatic COVID-19 caused by the ancestral strain. Our results support UB-612 as a potential potent booster against current and emerging SARS-CoV-2 variants.

Transmission dynamics of SARS-CoV-2 in a strictly-Orthodox Jewish community in the UK.

Some social settings such as households and workplaces, have been identified as high risk for SARS-CoV-2 transmission. Identifying and quantifying the importance of these settings is critical for designing interventions. A tightly-knit religious community in the UK experienced a very large COVID-19 epidemic in 2020, reaching 64.3% seroprevalence within 10 months, and we surveyed this community both for serological status and individual-level attendance at particular settings. Using these data, and a network model of people and places represented as a stochastic graph rewriting system, we estimated the relative contribution of transmission in households, schools and religious institutions to the epidemic, and the relative risk of infection in each of these settings. All congregate settings were important for transmission, with some such as primary schools and places of worship having a higher share of transmission than others. We found that the model needed a higher general-community transmission rate for women (3.3-fold), and lower susceptibility to infection in children to recreate the observed serological data. The precise share of transmission in each place was related to assumptions about the internal structure of those places. Identification of key settings of transmission can allow public health interventions to be targeted at these locations.

Specialised minds: extending adaptive explanations of personality to the evolution of psychopathology.

Traditional evolutionary theory invoked natural and sexual selection to explain species- and sex-typical traits. However, some heritable inter-individual variability in behaviour and psychology - personality - is probably adaptive. Here we extend this insight to common psychopathological traits. Reviewing key findings from three background areas of importance - theoretical models, non-human personality and evolved human social dynamics - we propose that a combination of social niche specialisation, negative frequency-dependency, balancing selection and adaptive developmental plasticity should explain adaptation for individual differences in psychology - 'specialised minds' - explaining some variance in personality and psychopathology trait dimensions, which share various characteristics. We suggest that anthropological research of behavioural differences should be extended past broad demographic factors (age and sex) to include individual specialisations. As a first step towards grounding psychopathology in ancestral social structure, we propose a minimum plausible prevalence, given likely ancestral group sizes, for negatively frequency-dependent phenotypes to be maintained as specialised tails of adaptive distributions - below the calculated prevalence, specialisation is highly unlikely. For instance, chronic highly debilitating forms of autism or schizophrenia are too rare for such explanations, whereas attention-deficit-hyperactivity disorder and broad autism phenotypes are common enough to have existed in most hunter-gatherer bands, making adaptive explanations more plausible.

Towards a population-based threshold of protection for COVID-19 vaccines.

Correlates of protection for COVID-19 vaccines are urgently needed to license additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological platform. IgG anti-Spike antibodies were highly correlated with ID50 neutralization in a validated pseudoviral assay and correlated significantly with efficacies for protection against infection with wild-type, alpha and delta variant SARS-CoV-2 virus. The protective threshold for each vaccine was calculated for IgG anti-Spike antibody. The mean protective threshold for all vaccine studies for WT virus was 154 BAU/ml (95 %CI 42-559), and for studies with antibody distributions that enabled precise estimation of thresholds (i.e. leaving out 2-dose mRNA regimens) was 60 BAU/ml (95 %CI 35-102). We propose that the proportion of individuals with responses above the appropriate protective threshold together with the geometric mean concentration can be used in comparative non-inferiority studies with licensed vaccines to ensure that new vaccines will be efficacious.