Background
Current clinical practice guidelines (CPGs) for posttraumatic stress disorder (PTSD) offer contradictory recommendations regarding use of medications or psychotherapy as first‐line ...treatment. Direct head‐to‐head comparisons are lacking.
Methods
Systemic review of Medline, EMBASE, PILOTS, Cochrane Central Register of Controlled Trials, PsycINFO, and Global Health Library was conducted without language restrictions. Randomized clinical trials ≥8 weeks in duration using structured clinical interview‐based outcome measures, active‐control conditions (e.g. supportive psychotherapy), and intent‐to‐treat analysis were selected for analyses. Independent review, data ion, and bias assessment were performed using standardized processes. Study outcomes were grouped around conventional follow‐up time periods (3, 6, and 9 months). Combined effect sizes were computed using meta‐analyses for medication versus control, medication pre‐/posttreatment, psychotherapy versus control, and psychotherapy pre‐/posttreatment.
Results
Effect sizes for trauma‐focused psychotherapies (TFPs) versus active control conditions were greater than medications versus placebo and other psychotherapies versus active controls. TFPs resulted in greater sustained benefit over time than medications. Sertraline, venlafaxine, and nefazodone outperformed other medications, although potential for methodological biases were high. Improvement following paroxetine and fluoxetine treatment was small. Venlafaxine and stress inoculation training (SIT) demonstrated large initial effects that decreased over time. Bupropion, citalopram, divalproex, mirtazapine, tiagabine, and topiramate failed to differentiate from placebo. Aripiprazole, divalproex, guanfacine, and olanzapine failed to differentiate from placebo when combined with an antidepressant.
Conclusions
Study findings support use of TFPs over nontrauma‐focused psychotherapy or medication as first‐line interventions. Second‐line interventions include SIT, and potentially sertraline or venlafaxine, rather than entire classes of medication, such as SSRIs. Future revisions of CPGs should prioritize studies that utilize active controls over waitlist or treatment‐as‐usual conditions. Direct head‐to‐head trials of TFPs versus sertraline or venlafaxine are needed.
The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and ...effectiveness of these vaccines in a UK community setting.
In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/m2vs ≥30 kg/m2), and comorbidities (binary variable, with or without comorbidities).
Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49–68) for ChAdOx1 nCoV-19 and 69% (66–72) for BNT162b2 at 21–44 days and 72% (63–79) for BNT162b2 after 45–59 days.
Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days.
ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.
Upper mantle anisotropy has been mapped beneath continents at high spatial resolution. Beneath the oceans, however, shear wave splitting constraints on upper mantle anisotropy are sparse, due to the ...paucity of seismic receivers. A technique that does not require the availability of seismic stations close to the region under study is differential PS‐SKS splitting. Here, we use global wavefield simulations to investigate circumstances under which PS‐SKS splitting can be applied, and then use this technique to measure upper mantle anisotropy beneath the Pacific Ocean basin. Our results demonstrate that upper mantle anisotropy in our study region mostly reflects shearing due to the Pacific plate. North of Fiji, we observe a rotation of fast polarization directions, away from the direction of absolute plate motion of the Pacific plate. This may reflect far‐field mantle flow effects associated with the subduction of the Australian plate beneath the Pacific.
Plain Language Summary
Earthquakes cause seismic waves whose speeds sometimes depend on their polarization and propagation direction. This material property, called seismic anisotropy, can be used to infer the direction of flow in Earth's upper mantle. Seismic anisotropy is straightforward to measure directly beneath a seismic station, but harder to study if station coverage is sparse. We use a technique that allows us to infer upper mantle seismic anisotropy beneath the Pacific Ocean in places without nearby seismic stations. Our measurements show that while seismic anisotropy varies laterally beneath the Pacific Ocean, in most cases it can be explained by the movement of the Pacific tectonic plate, leading to horizontal shearing of the underlying mantle. North of Fiji, we can observe the effects that the subduction of the Australian beneath the Pacific tectonic plate has on upper mantle flow.
Key Points
We test the robustness of differential PS‐SKS shear‐wave splitting measurements to characterize anisotropy near the PS bounce point
We use this technique infer seismic anisotropy beneath the Pacific Ocean
A majority of our measurements can be explained by plate motion induced shearing beneath the Pacific plate
A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who ...reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.
COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to ...identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness.
This prospective, community-based, nested, case-control study used self-reported data (eg, on demographics, geographical location, health risk factors, and COVID-19 test results, symptoms, and vaccinations) from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile phone app. For the risk factor analysis, cases had received a first or second dose of a COVID-19 vaccine between Dec 8, 2020, and July 4, 2021; had either a positive COVID-19 test at least 14 days after their first vaccination (but before their second; cases 1) or a positive test at least 7 days after their second vaccination (cases 2); and had no positive test before vaccination. Two control groups were selected (who also had not tested positive for SARS-CoV-2 before vaccination): users reporting a negative test at least 14 days after their first vaccination but before their second (controls 1) and users reporting a negative test at least 7 days after their second vaccination (controls 2). Controls 1 and controls 2 were matched (1:1) with cases 1 and cases 2, respectively, by the date of the post-vaccination test, health-care worker status, and sex. In the disease profile analysis, we sub-selected participants from cases 1 and cases 2 who had used the app for at least 14 consecutive days after testing positive for SARS-CoV-2 (cases 3 and cases 4, respectively). Controls 3 and controls 4 were unvaccinated participants reporting a positive SARS-CoV-2 test who had used the app for at least 14 consecutive days after the test, and were matched (1:1) with cases 3 and 4, respectively, by the date of the positive test, health-care worker status, sex, body-mass index (BMI), and age. We used univariate logistic regression models (adjusted for age, BMI, and sex) to analyse the associations between risk factors and post-vaccination infection, and the associations of individual symptoms, overall disease duration, and disease severity with vaccination status.
Between Dec 8, 2020, and July 4, 2021, 1 240 009 COVID Symptom Study app users reported a first vaccine dose, of whom 6030 (0·5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971 504 reported a second dose, of whom 2370 (0·2%) subsequently tested positive for SARS-CoV-2 (cases 2). In the risk factor analysis, frailty was associated with post-vaccination infection in older adults (≥60 years) after their first vaccine dose (odds ratio OR 1·93, 95% CI 1·50–2·48; p<0·0001), and individuals living in highly deprived areas had increased odds of post-vaccination infection following their first vaccine dose (OR 1·11, 95% CI 1·01–1·23; p=0·039). Individuals without obesity (BMI <30 kg/m2) had lower odds of infection following their first vaccine dose (OR 0·84, 95% CI 0·75–0·94; p=0·0030). For the disease profile analysis, 3825 users from cases 1 were included in cases 3 and 906 users from cases 2 were included in cases 4. Vaccination (compared with no vaccination) was associated with reduced odds of hospitalisation or having more than five symptoms in the first week of illness following the first or second dose, and long-duration (≥28 days) symptoms following the second dose. Almost all symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals, and vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older.
To minimise SARS-CoV-2 infection, at-risk populations must be targeted in efforts to boost vaccine effectiveness and infection control measures. Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era, particularly around frail older adults and individuals living in more deprived areas, even if these individuals are vaccinated, and might have implications for strategies such as booster vaccinations.
ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, and the Alzheimer's Society.
Ultralow velocity zones (ULVZs) and seismic anisotropy are both commonly detected in the lowermost mantle at the edges of the two antipodal large low velocity provinces (LLVPs). The preferential ...occurrences of both ULVZs and anisotropy at LLVP edges are potentially connected to deep mantle dynamics; however, the two phenomena are typically investigated separately. Here we use waveforms from three deep earthquakes to jointly investigate ULVZ structure and lowermost mantle anisotropy near an edge of the Pacific LLVP to the southeast of Hawaii. We model global wave propagation through candidate lowermost mantle structures using AxiSEM3D. Two structures that cause ULVZ‐characteristic postcursors in our data are identified and are modeled as cylindrical ULVZs with radii of ∼1° and ∼3° and velocity reductions of ∼36% and ∼20%. One of these features has not been detected before. The ULVZs are located to the south of Hawaii and are part of the previously detected complex low velocity structure at the base of the mantle in our study region. The waveforms also reveal that, to first order, the base of the mantle in our study region is a broad and thin region of modestly low velocities. Measurements of Sdiff shear wave splitting reveal evidence for lowermost mantle anisotropy that is approximately co‐located with ULVZ material. Our measurements of co‐located anisotropy and ULVZ material suggest plausible geodynamic scenarios for flow in the deep mantle near the Pacific LLVP edge.
Plain Language Summary
Earthquakes cause different types of seismic waves that can be used to create an image of seismically fast and slow regions within Earth's interior. Two large‐scale features with relatively low seismic velocities have been identified at the base of the mantle, one beneath Africa and one beneath the Pacific Ocean, known as large low velocity provinces (LLVPs). Small‐scale, thin features with extremely low velocities, known as ultralow velocity zones (ULVZs), have previously been detected just above the core‐mantle boundary, often located at the edges of the LLVPs. In this study, we investigate a region of the deep mantle at the edge of the Pacific LLVP. We use recordings of earthquake waves that have sampled this region to map two distinct ULVZ regions at this boundary. We also investigate a property known as seismic anisotropy, the directional dependence of seismic wave speeds, which can be used to infer the direction of mantle flow. We outline several potential mantle flow scenarios that are consistent with our data, helping to understand flow processes at the edges of LLVP structures in the deep mantle.
Key Points
We identify and characterize a previously undetected ultralow velocity zone (ULVZ) beneath the central Pacific Ocean
We propose the existence of a thin and broad layer with low seismic velocities in our study region, just above the core‐mantle boundary
Measurements of potentially co‐located seismic anisotropy and ULVZ structure allow the inference of plausible dynamics in the deep mantle
Gut transit time is a key modulator of host-microbiome interactions, yet this is often overlooked, partly because reliable methods are typically expensive or burdensome. The aim of this single-arm, ...single-blinded intervention study is to assess (1) the relationship between gut transit time and the human gut microbiome, and (2) the utility of the 'blue dye' method as an inexpensive and scalable technique to measure transit time.
We assessed interactions between the taxonomic and functional potential profiles of the gut microbiome (profiled via shotgun metagenomic sequencing), gut transit time (measured via the blue dye method), cardiometabolic health and diet in 863 healthy individuals from the PREDICT 1 study.
We found that gut microbiome taxonomic composition can accurately discriminate between gut transit time classes (0.82 area under the receiver operating characteristic curve) and longer gut transit time is linked with specific microbial species such as
,
spp and
spp (false discovery rate-adjusted p values <0.01). The blue dye measure of gut transit time had the strongest association with the gut microbiome over typical transit time proxies such as stool consistency and frequency.
Gut transit time, measured via the blue dye method, is a more informative marker of gut microbiome function than traditional measures of stool consistency and frequency. The blue dye method can be applied in large-scale epidemiological studies to advance diet-microbiome-health research. Clinical trial registry website https://clinicaltrials.gov/ct2/show/NCT03479866 and trial number NCT03479866.
Worldwide, racial and ethnic minorities have been disproportionately impacted by COVID-19 with increased risk of infection, its related complications, and death. In the initial phase of ...population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy may result in differences in uptake. We performed a cohort study among U.S. and U.K. participants who volunteered to take part in the smartphone-based COVID Symptom Study (March 2020-February 2021) and used logistic regression to estimate odds ratios of vaccine hesitancy and uptake. In the U.S. (n = 87,388), compared to white participants, vaccine hesitancy was greater for Black and Hispanic participants and those reporting more than one or other race. In the U.K. (n = 1,254,294), racial and ethnic minority participants showed similar levels of vaccine hesitancy to the U.S. However, associations between participant race and ethnicity and levels of vaccine uptake were observed to be different in the U.S. and the U.K. studies. Among U.S. participants, vaccine uptake was significantly lower among Black participants, which persisted among participants that self-reported being vaccine-willing. In contrast, statistically significant racial and ethnic disparities in vaccine uptake were not observed in the U.K sample. In this study of self-reported vaccine hesitancy and uptake, lower levels of vaccine uptake in Black participants in the U.S. during the initial vaccine rollout may be attributable to both hesitancy and disparities in access.
Given the continued burden of COVID-19 worldwide, there is a high unmet need for data on the effect of social distancing and face mask use to mitigate the risk of COVID-19. We examined the ...association of community-level social distancing measures and individual face mask use with risk of predicted COVID-19 in a large prospective U.S. cohort study of 198,077 participants. Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported 'always' use of face mask was associated with a 62% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing. These findings provide support for the efficacy of mask-wearing even in settings of poor social distancing in reducing COVID-19 transmission. Despite mass vaccination campaigns in many parts of the world, continued efforts at social distancing and face mask use remain critically important in reducing the spread of COVID-19.
Many regions of the Earth's mantle are seismically anisotropic, including portions of the lowermost mantle, which may indicate deformation due to convective flow. The splitting of ScS phases, which ...reflect once off the core-mantle boundary (CMB), is commonly measured to identify lowermost mantle anisotropy, although some challenges exist. Here, we use global wavefield simulations to evaluate commonly used approaches to inferring a lowermost mantle contribution to ScS splitting. We show that due to effects of the CMB reflection, only the epicentral distance range between 60° and 70° is appropriate for ScS splitting measurements. For this distance range, splitting is diagnostic of deep mantle anisotropy if no upper mantle anisotropy is present; however, if ScS is also split due to upper mantle anisotropy, the reliable diagnosis of deep mantle anisotropy is challenging. Moreover, even in the case of a homogeneously anisotropic deep mantle region sampled from a single azimuth by multiple ScS waves with different source polarizations (in absence of upper mantle anisotropy), different apparent fast directions are produced. We suggest that ScS splitting should only be measured at "null" stations and conduct such an analysis worldwide. Our results indicate that seismic anisotropy is globally widespread in the deep mantle.
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