Nevin Manimala

Philos Trans R Soc Lond B Biol Sci. 2022 Aug 15;377(1857):20210394. doi: 10.1098/rstb.2021.0394. Epub 2022 Jun 27.

ABSTRACT

Temperature overshoot pathways entail exceeding a specified global warming level (e.g. 1.5°C or 2°C) followed by a decline in warming, achieved through anthropogenically enhanced CO₂ removal from the atmosphere. However, risks to biodiversity from temperature overshoot pathways are poorly described. Here, we explore biodiversity risks from overshoot by synthesizing existing knowledge and quantifying the dynamics of exposure and de-exposure to potentially dangerous temperatures for more than 30 000 species for a 2°C overshoot scenario. Our results suggest that climate risk to biodiversity from temperature overshoot pathways will arrive suddenly, but decrease only gradually. Peak exposure for biodiversity occurs around the same time as peak global warming, but the rate of de-exposure lags behind the temperature decline. While the global overshoot period lasts around 60 years, the duration of elevated exposure of marine and terrestrial biodiversity is substantially longer (around 100 and 130 years, respectively), with some ecological communities never returning to pre-overshoot exposure levels. Key biodiversity impacts may be irreversible and reliance on widespread CO₂ removal to reduce warming poses additional risks to biodiversity through altered land use. Avoiding any temperature overshoot must be a priority for reducing biodiversity risks from climate change, followed by limiting the magnitude and duration of any overshoot. More integrated models that include direct and indirect impacts from overshoot are needed to inform policy. This article is part of the theme issue ‘Ecological complexity and the biosphere: the next 30 years’.

PMID:35757884 | DOI:10.1098/rstb.2021.0394

Mycoses. 2022 Jun 27. doi: 10.1111/myc.13488. Online ahead of print.

ABSTRACT

BACKGROUND: The diagnostic accuracy of immunoassays versus immunoprecipitation methods for detecting A.fumigatus-specific IgG in patients with allergic bronchopulmonary aspergillosis (ABPA) complicating asthma remains unclear.

METHODS: We performed a systematic review to identify studies describing both the methods in the same ABPA subjects. We assessed study quality using the QUADAS-2 tool. We derived the relative sensitivity and specificity using the HSROC meta-regression model. We calculated the number-needed-to-test using an immunoassay to detect one additional positive test in ABPA.

RESULTS: Our search yielded 20 studies (796 ABPA, 929 controls). The studies had a high risk of bias. The summary estimates for sensitivity and specificity of immunoprecipitation methods were 68.6% (95% CI, 48.4-83.5) and 93.8% (95% CI, 83.6-97.8), while for immunoassays they were 85.2% (95% CI, 73.3-92.3) and 84.6% (95% CI, 76.0-90.5), respectively. The relative sensitivity and specificity of immunoassays compared to immunoprecipitation tests were 1.29 (95% CI, 1.1-1.6) and 0.91 (95% CI, 0.85-0.97), respectively. The automated immunoassays (1.77; 95% CI, 1.1-2.8) had better relative sensitivity than the manual (1.1; 95% CI, 1.02-1.18) assays compared to immunoprecipitation. The relative specificity of manual immunoassays (0.95; 95% CI, 0.91-0.99) was significantly lower, while that of automated (0.88; 95% CI, 0.77-1.0) assays was lower but not statistically different. One additional positive result was detected for every 6 (95% CI, 5-7) tests performed with immunoassay (versus immunoprecipitation).

CONCLUSION: Manual immunoassays have higher sensitivity and lower specificity, while automated immunoassays have higher sensitivity and similar specificity than immunoprecipitation methods for detecting A.fumigatus-IgG in patients with ABPA.

PMID:35757847 | DOI:10.1111/myc.13488

IJID Reg. 2021 Oct 28;1:100-106. doi: 10.1016/j.ijregi.2021.10.006. eCollection 2021 Dec.

ABSTRACT

OBJECTIVES: Outbreaks of Neisseria meningitidis have reached alarming levels due to the pathogen’s ability to cause severe complications, presenting as meningitis or septicemia. Our study reports the results of the first wide-scale surveillance of meningococcal meningitis in Iraq.

METHODS: The study included all consecutive cases of clinically suspected meningitis between June 2018 and May 2020 at 18 major hospitals around Iraq (n = 2314). Laboratory analysis of biological samples and real-time polymerase chain reaction tests were conducted to confirm bacterial etiology. Demographical and medical data were collected for statistical analysis.

RESULTS: In total, 370 patients were confirmed to have bacterial meningitis (215 had N. meningitidis, 154 had Streptococcus pneumoniae, and one case had Haemophilus influenzae type b). The most common N. meningitidis serogroup was B (77.7%), followed by W (18.1%) and X (4.2%). The annual incidence rate of N. meningitidis per 100 000 population was 0.86, with the highest being in Karbala (1.52 per 100 000 population). Cases of meningococcal meningitis were more likely to occur in children younger than 15 (OR = 3.526), and in the winter (OR = 1.474).

CONCLUSIONS: Continuous surveillance of N. meningitidis is necessary in Iraq, and can only be achieved through improved detection methods. The incidence of meningococcal meningitis in Iraq warrants improved vaccination programs.

PMID:35757824 | PMC:PMC9216274 | DOI:10.1016/j.ijregi.2021.10.006

J Am Stat Assoc. 2022;117(537):348-360. doi: 10.1080/01621459.2020.1777138. Epub 2020 Aug 19.

ABSTRACT

We consider estimation of mean and covariance functions of functional snippets, which are short segments of functions possibly observed irregularly on an individual specific subinterval that is much shorter than the entire study interval. Estimation of the covariance function for functional snippets is challenging since information for the far off-diagonal regions of the covariance structure is completely missing. We address this difficulty by decomposing the covariance function into a variance function component and a correlation function component. The variance function can be effectively estimated nonparametrically, while the correlation part is modeled parametrically, possibly with an increasing number of parameters, to handle the missing information in the far off-diagonal regions. Both theoretical analysis and numerical simulations suggest that this hybrid strategy is effective. In addition, we propose a new estimator for the variance of measurement errors and analyze its asymptotic properties. This estimator is required for the estimation of the variance function from noisy measurements.

PMID:35757778 | PMC:PMC9216204 | DOI:10.1080/01621459.2020.1777138

J Am Stat Assoc. 2022;117(537):1-11. doi: 10.1080/01621459.2021.1906684. Epub 2021 May 19.

ABSTRACT

Cross-trait polygenic risk score (PRS) method has gained popularity for assessing genetic correlation of complex traits using summary statistics from biobank-scale genome-wide association studies (GWAS). However, empirical evidence has shown a common bias phenomenon that highly significant cross-trait PRS can only account for a very small amount of genetic variance (R ² can be < 1%) in independent testing GWAS. The aim of this paper is to investigate and address the bias phenomenon of cross-trait PRS in numerous GWAS applications. We show that the estimated genetic correlation can be asymptotically biased toward zero. A consistent cross-trait PRS estimator is then proposed to correct such asymptotic bias. In addition, we investigate whether or not SNP screening by GWAS p-values can lead to improved estimation and show the effect of overlapping samples among GWAS. We analyze GWAS summary statistics of reaction time and brain structural magnetic resonance imaging-based features measured in the Pediatric Imaging, Neurocognition, and Genetics study. We find that the raw cross-trait PRS estimators heavily underestimate the genetic similarity between cognitive function and human brain structures (mean R ² = 1.32%), whereas the bias-corrected estimators uncover the moderate degree of genetic overlap between these closely related heritable traits (mean R ² = 22.42%). Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.

PMID:35757777 | PMC:PMC9232179 | DOI:10.1080/01621459.2021.1906684

Front Immunol. 2022 Jun 10;13:910337. doi: 10.3389/fimmu.2022.910337. eCollection 2022.

ABSTRACT

PURPOSE: To report the demographic, clinical, and laboratory characteristics of ocular syphilis based on a 6-year case series study from an eye center in East-China.

METHODS: A total of 131 cases (191 eyes) of ocular syphilis and the annual number of total syphilis cases from January 2016 to December 2021, were included in this study. Detailed medical records including systemic and ophthalmic medical history, a complete ophthalmic examination, color fundus photography, B-type ultrasound, fundus fluorescein angiography (FFA), spectral domain optical coherence tomography (SD-OCT), laboratory tests of the serum and cerebrospinal fluid (CSF) samples, as well as visual field test and orbital or cranial MRI in cases with suspected optic neuritis or optic atrophy, were collected and analyzed. Pearson Chi-square or Fisher’s exact tests was used for statistics analysis.

RESULTS: Of the 131 cases with ocular syphilis, 86 cases were in men and 6 cases had a past medical history or systemic manifestation of syphilis. HIV was found in only 2 of 70 cases undergoing serum HIV test. The average age was 54.0 years, ranging from 26-85 years. The average percentage of ocular syphilis out from the total syphilis cases was 5.1%, the average titer of serum rapid plasma regain (RPR) at presentation was 1:32, ranging from 1:1-1:512. The most predominant manifestation of ocular syphilis was posterior uveitis, followed by optic neuritis, optic atrophy, panuveitis, retinal vasculitis, and retinitis. The median of BCVA of all 191 eyes was 20/200 (ranging from no light perception to 20/20), and 20/40 (ranging from no light perception to 20/20) at presentation and final follow-up, respectively. Ocular syphilis with active inflammation responded well to penicillin therapy, no matter the initial visual acuity, ocular disease type, or RPR titers, as long as it was diagnosed early and treated properly and promptly. However, cases with optic atrophy, acute retinal necrosis, late diagnosis, permanent disruption, or loss of outer segment of photoreceptors of macular retina on SD-OCT showed poor visual improvement after therapy.

CONCLUSIONS: Early diagnosis of ocular syphilis is still challenging in clinical practice and syphilis tests should be routinely performed in patients with uveitis, retinitis, optic neuritis, and optic atrophy.

PMID:35757732 | PMC:PMC9226556 | DOI:10.3389/fimmu.2022.910337

Intern Emerg Med. 2022 Jun 26. doi: 10.1007/s11739-022-03028-3. Online ahead of print.

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination plays a crucial role as pivotal strategy to curb the coronavirus disease-19 (COVID-19) pandemic. The present study described the clinical status of patients affected by idiopathic inflammatory myopathies (IIM) after COVID-19 vaccination to assess the number of relapses. We included all patients affected by IIM and followed by Myositis Clinic, Rheumatology and Respiratory Diseases Units, Siena University Hospital, Bari University Hospital, Policlinico Umberto I, Sapienza University, Rome, and Policlinico Paolo Giaccone, Palermo. They underwent a telephone survey. A total of 119 IIM patients (median, IQR 58 (47-66) years; 32males; 50 dermatomyositis, 39 polymyositis and 30 anti-synthetase syndrome) were consecutively enrolled. Except four patients who refused the vaccination, 94 (81.7%) received Comirnaty, 16 (13.9%) Spikevax, 5 (4.4%) Vaxzevria. Seven (6.1%) patients had flare after vaccination. One of them had life-threatening systemic involvement and died two months after second dose of COVID-19 vaccination. From logistic regression analysis, Chi²-log ratio = 0.045,the variable that most influences the development of flare was the number of organs involved (p = 0.047). Sixty-eight patients received the third dose of COVID-19 vaccination: 51(75%) Comirnaty and 17 (25%) Moderna. No patients had flares after third dose. Our study represents the largest cohort of IIM patients in which the incidence of recurrence after anti-SARS-CoV-2 vaccine was assessed. In line with real-life data from other diseases, we found a clinical non-statistically significant risk of relapse in our patients, which occurred seldom, usually mild and in patients with a more severe and aggressive course of disease.

PMID:35754076 | DOI:10.1007/s11739-022-03028-3

Int Urol Nephrol. 2022 Jun 27. doi: 10.1007/s11255-022-03264-8. Online ahead of print.

ABSTRACT

BACKGROUND: International guidelines vary in terms of their definition and recommendation for management of low-risk non-muscle-invasive bladder cancer (LRNMIBC). The ideal management for this large subset of bladder cancer patient remains unclear.

OBJECTIVE: To evaluate long-term outcomes of patients with LRNMIBC. As a secondary objective, to assess for intergroup heterogeneity in disease-specific outcomes between G1 and G2LG diseases.

METHODS: A multi-centre, retrospective study of patients who met the 2015 NICE definition of LRNMIBC. Timeline of diagnosis ranged from 01/01/2012 to 30/06/2016.

RESULTS: A total 390 patients had available follow-up data (G1: 142, G2LG: 249). Over a median follow-up time of 36 months (IQR 25-50), 29.2% of the patients developed a recurrence. G2LG patients were statistically more likely to develop a recurrence (G1: 26.8%, G2LG: 33.7%, p < 0.05). 51.8% of recurrences occurred after 1 year of surveillance. Progression to high-grade disease occurred in 1.8% (n = 7, G1: 3, G2LG: 4) and a further 1.0% (n = 4, G1:3, G2LG: 1) of patients developed muscle-invasive bladder cancer (MIBC).

CONCLUSION: The majority of recurrences occurred after 1 year of surveillance. The risk of disease progression was low; however, this was observed in a cohort of patients with regular cystoscopic follow-up. The risk may be higher if patients were pre-maturely discharged. If a 5-year surveillance programme were to be followed, 96.5% of recurrences would be captured. Lastly, there appears to be intergroup heterogeneity within LRNMIBC with G2LG patients having a statistically higher risk of recurrence compared to G1.

PMID:35754065 | DOI:10.1007/s11255-022-03264-8

Neuroradiology. 2022 Jun 27. doi: 10.1007/s00234-022-02998-7. Online ahead of print.

ABSTRACT

PURPOSE: To assess the ability of 7 T MRI to detect hippocampal DWI lesions in the acute phase of TGA compared to 1.5 T/3 T MRI.

METHODS: Patients with a clinical diagnosis consistent with TGA and a 1.5/3 T MRI underwent an additional 7 T MRI when the 7 T system was available for clinical use, thus serving as their own controls.

RESULTS: Thirteen TGA patients with a median age of 68.5 years (range 46-77 years) were included and imaged at 1.5/3 T (median 17 h after onset of symptoms, range 3-23 h) and 7 T (median 23 h after onset, range 15-46 h). The 7 T MRIs were performed a median of 15 h after the 1.5/3 T MRIs (range 1-28 h). At 1.5/3 T, six patients (46%) were found to have at least one hippocampal DWI-lesions supporting the TGA diagnosis, which increased to 11 patients (85%) when examined at 7 T (p = 0.03). At 1.5/3 T, nine hippocampal DWI lesions were detected, which increased to 19 at 7 T, giving an increased detection rate of 111% (p = 0.002). Both neuroradiologists found the hippocampal DWI lesions at 7 T to have higher conspicuity and be easier to categorize as true findings compared to 1.5/3 T.

CONCLUSION: Seven-Tesla MRI showed both a statistically significant increase in the total number of detected hippocampal DWI lesions and the proportion of patients with at least one hippocampal DWI lesion supporting the TGA diagnosis compared to 1.5/3 T. Clinical use of 7 T will increase the number of patients having their TGA diagnosis supported by MRI, which can be especially useful in patients with negative 1.5/3 T MRI and low clinical certainty.

PMID:35754063 | DOI:10.1007/s00234-022-02998-7

Eur J Hum Genet. 2022 Jun 27. doi: 10.1038/s41431-022-01138-2. Online ahead of print.

ABSTRACT

Duchenne muscular dystrophy (DMD), an X-linked recessive condition is maternally inherited in two-thirds of affected boys. It is important to establish carrier status of female relatives to restore reproductive confidence for non-carriers and facilitate reproductive options and cardiac surveillance for carriers. This study investigates disease incidence within an Australian model of cascade screening and evolving genetic diagnostic technologies. A retrospective population-based cohort study of all genetically and/or histopathologically confirmed males with DMD, born in New South Wales and the Australian Capital Territory was undertaken from 2002-2012. Cases were identified using state-wide molecular laboratory and clinical databases. The annual disease incidence and “theoretically” preventable cases were extrapolated over the study period. Proband genotype/phenotype, pedigree analysis, carrier-risk and extent of cascade screening were also determined. The cumulative incidence of disease was 19.7 per 100,000 male live births and 1 in 5076 live born males were diagnosed with DMD. Differences in disease incidence were not statistically different when compared between 2002-2007 and 2008-2012 (incidence rate ratio = 1.13, 95% CI 0.76-1.69, p = 0.52). The incidence rate ratio of theoretically preventable cases did not significantly change between 2002-2007 and 2008-2012 (incidence rate ratio = 2.07, 95% CI 0.58-9.21, p = 0.23). Current diagnostic and cascade screening models have limitations in their impact on disease incidence, due to a spectrum of logistical, patient and condition related factors. Innovative approaches to reduce DMD incidence may be better achieved by preconception or early pregnancy carrier screening, prenatal exome sequencing and newborn screening.

PMID:35754057 | DOI:10.1038/s41431-022-01138-2