Nevin Manimala

JAMA Psychiatry. 2021 May 26. doi: 10.1001/jamapsychiatry.2021.0959. Online ahead of print.

ABSTRACT

IMPORTANCE: Morning diurnal preference is associated with reduced risk of major depressive disorder (MDD); however, causality in this association is uncertain.

OBJECTIVE: To examine the association of genetically proxied morning diurnal preference with depression risk using mendelian randomization.

DESIGN, SETTING, AND PARTICIPANTS: This 2-sample mendelian randomization study used summary-level genetic associations with diurnal preference and MDD. Up to 340 genetic loci associated with diurnal preference in a meta-analysis of the UK Biobank and 23andMe cohorts were considered as genetic proxies for diurnal preference. The effect size of these variants was scaled using genetic associations with accelerometer-based measurement of sleep midpoint. Genetic associations with MDD were obtained from a meta-analysis of genome-wide association studies data from the Psychiatric Genomics Consortium and UK Biobank. The inverse-variance weighted method was used to estimate the association of genetically proxied morning diurnal preference, corresponding to a 1-hour earlier sleep midpoint, with MDD risk.

EXPOSURES: Morning diurnal preference scaled to a 1-hour earlier, objectively measured sleep midpoint.

MAIN OUTCOMES AND MEASURES: Risk of MDD, including self-reported and clinically diagnosed cases, as ascertained in meta-analyses of genome-wide association studies.

RESULTS: A total of 697 828 individuals (all of European ancestry) were in the UK Biobank and 23andMe cohorts; 85 502 in the UK Biobank had measurements of the sleep midpoint. A further 170 756 individuals with MDD and 329 443 control participants (all of European ancestry) were in the Psychiatric Genomics Consortium and UK Biobank data. Genetically proxied earlier diurnal preference was associated with a 23% lower risk of depression (odds ratio [OR] per 1-hour earlier sleep midpoint, 0.77 [95% CI, 0.63-0.94]; P = .01). This association was similar when restricting analysis to individuals with MDD as stringently defined by the Psychiatric Genomics Consortium (OR, 0.73 [95% CI, 0.54-1.00]; P = .05) but not statistically significant when defined by hospital-based billing codes in the UK Biobank (OR, 0.64 [95% CI, 0.39-1.06]; P = .08). Sensitivity analyses examining potential bias due to pleiotropy or reverse causality showed similar findings (eg, intercept [SE], 0.00 [0.001]; P = .66 by Egger intercept test).

CONCLUSIONS AND RELEVANCE: The results of this mendelian randomization study support a protective association of earlier diurnal preference with risk of MDD and provide estimates contextualized to an objective sleep timing measure. Further investigation in the form of randomized clinical trials may be warranted.

PMID:34037671 | DOI:10.1001/jamapsychiatry.2021.0959

JAMA. 2021 May 26. doi: 10.1001/jama.2021.8565. Online ahead of print.

ABSTRACT

IMPORTANCE: Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed.

OBJECTIVE: To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines.

DESIGN, SETTING, AND PARTICIPANTS: Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively.

INTERVENTIONS: Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)-only control (n = 13 458); they received 2 intramuscular injections 21 days apart.

MAIN OUTCOMES AND MEASURES: The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose.

RESULTS: Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase-polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P < .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]).

CONCLUSIONS AND RELEVANCE: In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04510207; Chinese Clinical Trial Registry: ChiCTR2000034780.

PMID:34037666 | DOI:10.1001/jama.2021.8565

Environ Sci Process Impacts. 2021 May 26;23(5):699-713. doi: 10.1039/d0em00504e.

ABSTRACT

Volatile organic compounds (VOCs) are a key class of atmospheric emission released from highly complex petrochemical, transport and solvent sources both outdoors and indoors. This study established the concentrations and speciation of VOCs in 60 homes (204 individuals, 360 × 72 h samples, 40 species) in summer and winter, along with outdoor controls. Self-reported daily statistics were collected in each home on the use of cleaning, household and personal care products, all of which are known to release VOCs. Frequency of product use varied widely: deodorants: 2.9 uses home per day; sealant-mastics 0.02 uses home per day. The total concentration of VOCs indoors (range C2-C10) was highly variable between homes e.g. range 16.6-8150 μg m-3 in winter. Indoor concentrations of VOCs exceeded outdoor for 84% of households studied in summer and 100% of homes in winter. The most abundant VOCs found indoors in this study were n-butane (wintertime range: 1.5-4630 μg m-3), likely released as aerosol propellant, ethanol, acetone and propane. The cumulative use VOC-containing products over multiday timescales by occupants provided little predictive power to infer 72 hour averaged indoor concentrations. However, there was weak covariance between the cumulative usage of certain products and individual VOCs. From a domestic emissions perspective, reducing the use of hydrocarbon-based aerosol propellants indoors would likely have the largest impact.

PMID:34037627 | DOI:10.1039/d0em00504e

Nat Commun. 2021 May 25;12(1):3152. doi: 10.1038/s41467-021-22889-4.

ABSTRACT

The analysis of whole-genome sequencing studies is challenging due to the large number of rare variants in noncoding regions and the lack of natural units for testing. We propose a statistical method to detect and localize rare and common risk variants in whole-genome sequencing studies based on a recently developed knockoff framework. It can (1) prioritize causal variants over associations due to linkage disequilibrium thereby improving interpretability; (2) help distinguish the signal due to rare variants from shadow effects of significant common variants nearby; (3) integrate multiple knockoffs for improved power, stability, and reproducibility; and (4) flexibly incorporate state-of-the-art and future association tests to achieve the benefits proposed here. In applications to whole-genome sequencing data from the Alzheimer’s Disease Sequencing Project (ADSP) and COPDGene samples from NHLBI Trans-Omics for Precision Medicine (TOPMed) Program we show that our method compared with conventional association tests can lead to substantially more discoveries.

PMID:34035245 | DOI:10.1038/s41467-021-22889-4

Light Sci Appl. 2021 May 25;10(1):106. doi: 10.1038/s41377-021-00539-0.

ABSTRACT

Is it possible that a measurement of a spin component of a spin-1/2 particle yields the value 100? In 1988 Aharonov, Albert and Vaidman argued that upon pre- and postselection of particular spin states, weakening the coupling of a standard measurement procedure ensures this paradoxical result¹. This theoretical prediction, called weak value, was realised in numerous experiments^2-9, but its meaning remains very controversial^10-19, since its “anomalous” nature, i.e., the possibility to exceed the eigenvalue spectrum, as well as its “quantumness” are debated^20-22. We address these questions by presenting the first experiment measuring anomalous weak values with just a single click, without the need for statistical averaging. The measurement uncertainty is significantly smaller than the gap between the measured weak value and the nearest eigenvalue. Beyond clarifying the meaning of weak values, demonstrating their non-statistical, single-particle nature, this result represents a breakthrough in understanding the foundations of quantum measurement, showing unprecedented measurement capability for further applications of weak values to quantum photonics.

PMID:34035219 | DOI:10.1038/s41377-021-00539-0

Biomed Phys Eng Express. 2020 Nov 9;6(6). doi: 10.1088/2057-1976/abc634.

ABSTRACT

Hypertension is the condition where the normal blood pressure is high. This situation is manifested by the high pressure of the blood in the vein towards the vessel wall. Hypertension mostly affects the brain, kidneys, eyes, arteries and heart. Therefore, the diagnosis of this common disease is important. It may take days, weeks or even months for diagnosis. Often a device, called a blood pressure holter, is connected to the person for 24 or 48 h and the person’s blood pressure is recorded at certain intervals. Diagnosis can be made by the specialist physician considering these results. In recent years, various physiological measurement techniques have been used to accelerate this time-consuming diagnostic phase and intelligent models have been proposed. One of these techniques is photopletesmography (PPG). In this study, a model for the detection of hypertension disease in individuals was proposed using chirp z-transform and statistical features (total band power, autoregressive model parameters, standard deviation of signal’s derivative and zero crossing rate) of optimal band-pass filtered short-time PPG signals. The proposed method was successfully applied to 657 PPG trials, which each of them had only 2.1 s signal length and achieved a classification accuracy rate of 77.52% on the test data. The results showed that the diagnosis of hypertension can be performed effectively by chirp z-transform and statistical features and support vector machine classifier using optimal frequency range of 1.4-6 Hz.

PMID:34035194 | DOI:10.1088/2057-1976/abc634

Biomed Phys Eng Express. 2020 Oct 1;6(6). doi: 10.1088/2057-1976/abb5ea.

ABSTRACT

We present a method of directly optimizing on deviations in clinical goal values in radiation therapy treatment planning. Using a new mathematical framework in which metrics derived from the dose-volume histogram are regarded as functionals of an auxiliary random variable, we are able to obtain volume-at-dose and dose-at-volume as infinitely differentiable functions of the dose distribution with easily evaluable function values and gradients. Motivated by the connection to risk measures in finance, which is formalized in this framework, we also derive closed-form formulas for mean-tail-dose and demonstrate its capability of reducing extreme dose values in tail distributions. Numerical experiments performed on a prostate and a head-and-neck patient case show that the direct optimization of dose-volume histogram metrics produced marginally better results than or outperformed conventional planning objectives in terms of clinical goal fulfilment, control of low- and high-dose tails of target distributions and general plan quality defined by a pre-specified evaluation measure. The proposed framework eliminates the disconnect between optimization functions and evaluation metrics and may thus reduce the need for repetitive user interaction associated with conventional treatment planning. The method also has the potential of enhancing plan optimization in other settings such as multicriteria optimization and automated treatment planning.

PMID:34035188 | DOI:10.1088/2057-1976/abb5ea

J Neurointerv Surg. 2021 May 25:neurintsurg-2021-017502. doi: 10.1136/neurintsurg-2021-017502. Online ahead of print.

ABSTRACT

BACKGROUND: The effectiveness and safety of endovascular thrombectomy (EVT) for medium vessel occlusions (MeVO) in the anterior intracranial circulation for patients with acute ischemic stroke (AIS) has yet to be definitively established. We compared outcomes in patients undergoing EVT for large vessel occlusion (LVO) versus those with MeVO.

METHODS: This retrospective cohort study, using an intention to treat design, compared the 90-day modified Rankin Scale (mRS) score between 43 patients with MeVO and 199 with LVO in the anterior intracranial circulation. Secondary outcome measures included vessel recanalization using the Thrombolysis in Cerebral Infarction (TICI) score, procedural complications, post-EVT intracranial hemorrhage (ICH), and infarct size.

RESULTS: The rate of good functional outcome (90-day mRS 0-2) was higher in patients with LVO than in those with MeVO (32.9% vs 27%), but this was not statistically significant (p=0.19). The rate of EVT procedural complications was also not significantly different between the groups (p=0.10), nor was the rate of ICH (p=0.30). There was also no significant difference in TICI scores between groups (p=0.12). Infarct size was larger in the LVO group (p<0.01). Multivariate analysis showed older age, not receiving recombinant tissue plasminogen activator (r-tPA), and larger infarct size were independent predictors of poor functional outcome at 90 days.

CONCLUSION: The 90-day mRS and rate of periprocedural complications were not significantly different between patients treated for LVO and those treated for MeVO with EVT. Older age, not receiving r-tPA, and larger infarct size were independent predictors of poor outcome at 90 days.

PMID:34035151 | DOI:10.1136/neurintsurg-2021-017502

BMJ Open. 2021 May 25;11(5):e047790. doi: 10.1136/bmjopen-2020-047790.

ABSTRACT

INTRODUCTION: Intubation-related complications are less frequent when intubation is successful on the first attempt. The rate of first attempt success in the emergency department (ED) and intensive care unit (ICU) is typically less than 90%. The bougie, a semirigid introducer that can be placed into the trachea to facilitate a Seldinger-like technique of tracheal intubation and is typically reserved for difficult or failed intubations, might improve first attempt success. Evidence supporting its use, however, is from a single academic ED with frequent bougie use. Validation of these findings is needed before widespread implementation.

METHODS AND ANALYSIS: The BOugie or stylet in patients Undergoing Intubation Emergently trial is a prospective, multicentre, non-blinded randomised trial being conducted in six EDs and six ICUs in the USA. The trial plans to enrol 1106 critically ill adults undergoing orotracheal intubation. Eligible patients are randomised 1:1 for the use of a bougie or use of an endotracheal tube with stylet for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcome is severe hypoxaemia, defined as an oxygen saturation less than 80% between induction until 2 min after completion of intubation. Enrolment began on 29 April 2019 and is expected to be completed in 2021.

ETHICS AND DISSEMINATION: The trial protocol was approved with waiver of informed consent by the Central Institutional Review Board at Vanderbilt University Medical Center or the local institutional review board at an enrolling site. The results will be submitted for publication in a peer-reviewed journal and presented at scientific conferences.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03928925).

PMID:34035106 | DOI:10.1136/bmjopen-2020-047790

BMJ Open. 2021 May 25;11(5):e047230. doi: 10.1136/bmjopen-2020-047230.

ABSTRACT

OBJECTIVES: We performed a cross-sectional analysis of data from the nationwide Korea National Health and Nutrition Examination Survey to evaluate the association between obesity and chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyp (CRSsNP).

DESIGN: Retrospective cross-sectional analysis of health survey data.

SETTING: Voluntary survey of representative South Korean populations.

PARTICIPANTS: In total, 32 384 individuals aged 19 years or older with available data on CRS and obesity were included.

PRIMARY AND SECONDARY OUTCOME MEASURES: Diagnosis of CRSwNP or CRSsNP was performed by trained otolaryngologists through sinus endoscopy and surveys of medical history. General and central obesity was diagnosed using body mass index (BMI) and waist circumference (WC), respectively.

METHODS: A multivariate logistic regression analysis was used to clarify the association between CRSwNP or CRSsNP and obesity according to BMI and WC. Non-obese individuals were recruited as controls.

RESULTS: The prevalence of CRSwNP was higher in the general (OR, 1.438; 95% CI, 1.170 to 1.768; p<0.001) and central (OR, 1.251; 95% CI, 1.031 to 1.520; p=0.033) obesity groups than in the control group. Prevalence of CRSsNP was not correlated with obesity. In a logistic regression analysis, olfactory dysfunction (OR, 1.329; 95% CI, 1.137 to 1.553; p<0.001) and purulent discharge (OR, 1.383; 95% CI, 1.193 to 1.603; p<0.001) showed a higher incidence in the central obesity group than in the control group.

CONCLUSIONS: We demonstrated an association between CRSwNP and general and central obesity. Further investigations on the mechanism underlying this correlation are necessary for an improved understanding of the pathogenesis of CRSwNP.

PMID:34035104 | DOI:10.1136/bmjopen-2020-047230