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A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.
Methods
This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.
Results
ES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.
Conclusions
Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.
Due to shortages of N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic, it is necessary to estimate the number of N95s required for healthcare workers (HCWs) to inform manufacturing targets and resource allocation.
Methods:
We developed a model to determine the number of N95 respirators needed for HCWs both in a single acute-care hospital and the United States.
Results:
For an acute-care hospital with 400 all-cause monthly admissions, the number of N95 respirators needed to manage COVID-19 patients admitted during a month ranges from 113 (95% interpercentile range [IPR], 50–229) if 0.5% of admissions are COVID-19 patients to 22,101 (95% IPR, 5,904–25,881) if 100% of admissions are COVID-19 patients (assuming single use per respirator, and 10 encounters between HCWs and each COVID-19 patient per day). The number of N95s needed decreases to a range of 22 (95% IPR, 10–43) to 4,445 (95% IPR, 1,975–8,684) if each N95 is used for 5 patient encounters. Varying monthly all-cause admissions to 2,000 requires 6,645–13,404 respirators with a 60% COVID-19 admission prevalence, 10 HCW–patient encounters, and reusing N95s 5–10 times. Nationally, the number of N95 respirators needed over the course of the pandemic ranges from 86 million (95% IPR, 37.1–200.6 million) to 1.6 billion (95% IPR, 0.7–3.6 billion) as 5%–90% of the population is exposed (single-use). This number ranges from 17.4 million (95% IPR, 7.3–41 million) to 312.3 million (95% IPR, 131.5–737.3 million) using each respirator for 5 encounters.
Conclusions:
We quantified the number of N95 respirators needed for a given acute-care hospital and nationally during the COVID-19 pandemic under varying conditions.
Wide-ranging outcomes have been reported for surgical and non-surgical management of T3 laryngeal carcinomas. This study compared the outcomes of T3 tumours treated with laryngectomy or (chemo)radiotherapy in the northeast of England.
Methods
The outcomes of T3 laryngeal carcinoma treatment at three centres (2007–2016) were retrospectively analysed using descriptive statistics and survival curves.
Results
Of 179 T3 laryngeal carcinomas, 68 were treated with laryngectomies, 57 with chemoradiotherapy and 32 with radiotherapy. There was no significant five-year survival difference between treatment with laryngectomy (34.1 per cent) and chemoradiotherapy (48.6 per cent) (p = 0.184). The five-year overall survival rate for radiotherapy (12.5 per cent) was significantly inferior compared to laryngectomy and chemoradiotherapy (p = 0.003 and p < 0.001, respectively). The recurrence rates were 22.1 per cent for laryngectomy, 17.5 per cent for chemoradiotherapy and 50 per cent for radiotherapy. There were significant differences in recurrence rates when laryngectomy (p = 0.005) and chemoradiotherapy (p = 0.001) were compared to radiotherapy.
Conclusion
Laryngectomy and chemoradiotherapy had significantly higher five-year overall survival and lower recurrence rates compared with radiotherapy alone. Laryngectomy should be considered in patients unsuitable for chemotherapy, as it may convey a significant survival advantage over radiotherapy alone.
This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.
Methods
Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.
Results
JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.
Conclusions
These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.
The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.
SPARC is designed to be a high-field, medium-size tokamak aimed at achieving net energy gain with ion cyclotron range-of-frequencies (ICRF) as its primary auxiliary heating mechanism. Empirical predictions with conservative physics indicate that SPARC baseline plasmas would reach $Q\approx 11$, which is well above its mission objective of $Q>2$. To build confidence that SPARC will be successful, physics-based integrated modelling has also been performed. The TRANSP code coupled with the theory-based trapped gyro-Landau fluid (TGLF) turbulence model and EPED predictions for pedestal stability find that $Q\approx 9$ is attainable in standard H-mode operation and confirms $Q > 2$ operation is feasible even with adverse assumptions. In this analysis, ion cyclotron waves are simulated with the full wave TORIC code and alpha heating is modelled with the Monte–Carlo fast ion NUBEAM module. Detailed analysis of expected turbulence regimes with linear and nonlinear CGYRO simulations is also presented, demonstrating that profile predictions with the TGLF reduced model are in reasonable agreement.
Ion cyclotron range of frequencies (ICRF) heating will be the sole auxiliary heating method on SPARC for both full-field (Bt0 ~ 12 T) D–T operation and reduced field (Bt0 ~ 8 T) D–D operation. Using the fast wave at ~120 MHz, good wave penetration and strong single-pass absorption is expected for D–T(3He), D(3He), D(H) and 4He(H) heating scenarios. The dependences of wave absorption on ${k_\parallel }$, 3He concentration, resonance location, antenna poloidal location and losses on alpha particles and ash have been studied. The antenna loading has been assessed by comparison with the Alcator C-Mod antennae. An antenna spectrum of ${k_\parallel }\sim 15\text{--}18\,{\textrm{m}^{ - 1}}$ is shown to be good for both core absorption and edge coupling. For the control of impurity sources, the antenna straps are rotated ~10° to be perpendicular to the B field and the straps can run with different power levels in order to optimize the antenna spectrum and to minimize the image current on the antenna frame. Combining the physics constraints with the SPARC port design, maintenance requirement and contingency against antenna failure during D–T operation, we plan to mount on the inner wall of the vacuum vessel a total of 12 4-strap antennae in 6 ports while keeping 3-strap antennae that are insertable and removable on port plugs as the backup option.
The main aim of the present studies is to determine whether, or to some extent, specific cognitive domains could differentiate the main subtypes of mood disorder in the depressed and clinically remitted status respectively.
Method
Three groups of bipolar I (n = 92), bipolar II (n = 131) and unipolar depression patients (n = 293) were tested with a battery of neuropsychological tests at baseline and after 6 weeks of treatment, contrasting with 202 healthy controls on cognitive performance.
Results
At the acute depressive state, the three patients groups (bipolar I, bipolar II and unipolar depression) showed cognitive dysfunction in processing speed, memory, verbal fluency and executive function but not attention compared with controls. And post comparisons revealed that bipolar I patients performed significantly worse in these impaired cognitive domain than bipolar II and unipolar depression patients in verbal fluency and executive function. After treatment, clinically remitted bipolar I and bipolar II patients only displayed cognitive impairment in processing speed and visual memory in relative to controls, while remitted unipolar depression patients showed cognitive impairment in executive function in addition to processing speed and visual memory.
Conclusion
Bipolar I, bipolar II and unipolar depression patients have a similar pattern of cognitive impairment during the state of acute depressive episodes. At the clinically remission, still both bipolar disorder and unipolar depression patients showed cognitive deficits in processing speed and visual memory, and executive dysfunction might be a status-maker for bipolar disorder, but a trait-marker for unipolar depression
Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene–environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum.
Methods
The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components).
Results
Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene–environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions.
Conclusions
The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.
Seasonal influenza virus epidemics have a major impact on healthcare systems. Data on population susceptibility to emerging influenza virus strains during the interepidemic period can guide planning for resource allocation of an upcoming influenza season. This study sought to assess the population susceptibility to representative emerging influenza virus strains collected during the interepidemic period. The microneutralisation antibody titers (MN titers) of a human serum panel against representative emerging influenza strains collected during the interepidemic period before the 2018/2019 winter influenza season (H1N1-inter and H3N2-inter) were compared with those against influenza strains representative of previous epidemics (H1N1-pre and H3N2-pre). A multifaceted approach, incorporating both genetic and antigenic data, was used in selecting these representative influenza virus strains for the MN assay. A significantly higher proportion of individuals had a ⩾four-fold reduction in MN titers between H1N1-inter and H1N1-pre than that between H3N2-inter and H3N2-pre (28.5% (127/445) vs. 4.9% (22/445), P < 0.001). The geometric mean titer (GMT) of H1N1-inter was significantly lower than that of H1N1-pre (381 (95% CI 339–428) vs. 713 (95% CI 641–792), P < 0.001), while there was no significant difference in the GMT between H3N2-inter and H3N2-pre. Since A(H1N1) predominated the 2018–2019 winter influenza epidemic, our results corroborated the epidemic subtype.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.
Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) have been considered prevalent pathogens in foot infections. However, whether empiric therapy directed against these organisms is necessary, and in whom to consider treatment, is rather unclear. The aim of this study was to develop predictive algorithms for forecasting the probability of isolating these organisms in the infected wounds of patients in a population where the prevalence of resistant pathogens is low. This was a retrospective study of regression model-based risk factor analysis that included 140 patients who presented with infected, culture positive foot ulcers to two urban hospitals. A total of 307 bacteria were identified, most frequently MRSA (11.1%). P. aeruginosa prevalence was 6.5%. In the multivariable analysis, amputation (odds ratio (OR) 5.75, 95% confidence interval (CI) 1.48–27.63), renal disease (OR 5.46, 95% CI 1.43–25.16) and gangrene (OR 2.78, 95% CI 0.82–9.59) were identified as risk factors associated with higher while diabetes (OR 0.07, 95% CI 0.01–0.34) and Infectious Diseases Society of America infection severity >3 (OR 0.18, 95% CI 0.03–0.65) were associated with lower odds of P. aeruginosa isolation (C statistic 0.81). Similar analysis for MRSA showed that amputation was associated with significantly lower (OR 0.29, 95% CI 0.09–0.79) risk, while history of MRSA infection (OR 5.63, 95% CI 1.56–20.63) and osteomyelitis (OR 2.523, 95% CI 1.00–6.79) was associated with higher odds of isolation (C statistic 0.69). We developed two predictive nomograms with reasonable to strong ability to discriminate between patients who were likely of being infected with P. aeruginosa or MRSA and those who were not. These analyses confirm the association of some, but also question the significance of other frequently described risk factors in predicting the isolation of these organisms.
The capture of volatile radioactive iodine-129 is an important process for nuclear fission. Biphenyl-bridged wrinkled mesoporous silica shows similar performance for iodine sequestration to commercial Ag-mordenite and avoids the use of expensive silver. The biphenyl-wrinkled mesoporous silica nanoparticles function as a scaffold for biphenyl groups and also as a fluorescent indicator for the loading of iodine. The nanoparticles have a surface area of 973 m2/g and the biphenyl molecules form an electron charge-transfer complex with iodine. Iodine was loaded into the biphenyl-bridged wrinkled mesoporous silica (BWMS) at 19 ± 0.2 % loading by mass.
Seismograms acquired on the McMurdo Ice Shelf, Antarctica, during an Austral summer melt season (November 2016–January 2017) reveal a diurnal cycle of seismicity, consisting of hundreds of thousands of small ice quakes limited to a 6–12 hour period during the evening, in an area where there is substantial subsurface melting. This cycle is explained by thermally induced bending and fracture of a frozen surface superimposed on a subsurface slush/water layer that is supported by solar radiation penetration and absorption. A simple, one-dimensional model of heat transfer driven by observed surface air temperature and shortwave absorption reproduces the presence and absence (as daily weather dictated) of the observed diurnal seismicity cycle. Seismic event statistics comparing event occurrence with amplitude suggest that the events are generated in a fractured medium featuring relatively low stresses, as is consistent with a frozen surface superimposed on subsurface slush. Waveforms of the icequakes are consistent with hydroacoustic phases at frequency
$ {\bf \gt} \bf 75\,{\bf Hz}$
and flexural-gravity waves at frequency
$ \bf {\bf \lt}25\,{\bf Hz}$
. Our results suggest that seismic observation may prove useful in monitoring subsurface melting in a manner that complements other ground-based methods as well as remote sensing.
Middle-third helical rim defects may arise from trauma or oncological resection, and pose a challenging reconstructive problem. Reconstructing defects larger than 2 cm using traditional methods commits patients to the inconvenience of staged procedures.
Method
This paper describes a single-stage helical rim reconstruction technique using a post-auricular bipedicled flap and ipsilateral conchal cartilage graft for delayed middle-third helical rim reconstruction.
Results
Two examples of this technique used in post-trauma and oncological reconstruction cases are presented, with pre- and post-operative photographs provided for demonstration.
Conclusion
Contralateral graft harvest and staged operations for helical rim reconstruction are associated with donor site morbidity and the inconvenience of multiple operations to achieve the desired reconstructive outcome. Our single-stage helical rim reconstruction technique was well tolerated by patients, and showed satisfactory aesthetic results in terms of size and symmetry.
During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.