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Nevin Manimala Statistics

A Computationally Efficient Monte-Carlo Model for Biomedical Raman Spectroscopy

J Biophotonics. 2021 Mar 18:e202000377. doi: 10.1002/jbio.202000377. Online ahead of print.

ABSTRACT

Monte Carlo (MC) modeling is a valuable tool to gain fundamental understanding of light-tissue interactions, provide guidance and assessment to optical instrument designs, and help analyze experimental data. It has been a major challenge to efficiently extend MC towards modeling of bulk-tissue Raman spectroscopy (RS) due to the wide spectral range, relatively sharp spectral features, and presence of background autofluorescence. Here, we report a computationally efficient MC approach for RS by adapting the massively-parallel Monte Carlo eXtreme (MCX) simulator. Simulation efficiency is achieved through “isoweight”, a novel approach that combines the statistical generation of Raman scattered and Fluorescence emission with a lookup-table-based technique well-suited for parallelization. The MC model uses a graphics processor to produce dense Raman and fluorescence spectra over a range of 800-2000cm-1 with an approximately 100x increase in speed over prior RS Monte Carlo methods. The simulated RS signals are compared against experimentally collected spectra from gelatin phantoms, showing a strong correlation. This article is protected by copyright. All rights reserved.

PMID:33733621 | DOI:10.1002/jbio.202000377

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Nevin Manimala Statistics

Conventional chemotherapy for Acute Myeloid Leukemia in older adults: impact on nutritional, cognitive and functional status

Eur J Haematol. 2021 Mar 18. doi: 10.1111/ejh.13624. Online ahead of print.

ABSTRACT

OBJECTIVES: The impact of conventional treatment for acute myeloid leukemia (AML) on the nutritional, cognitive, and functional status of elderly patients is seldom studied. This assessment was performed in the context of the LAMSA 2007 trial.

METHODS: The trial enrolled 424 patients with de novo AML. Among them, 316 benefited from geriatric assessment (GA) including nutritional, cognitive and functional status and were scored according to Eastern Cooperative Oncology Group (ECOG) and SORROR for the prediction of treatment toxicity, morbidity and mortality. Patients were investigated at diagnosis and three times during follow-up.

RESULTS: This study showed that AML and its treatment have no impact on cognitive (p=0.554) nor functional status (p=0.842 for Activity of Daily Living and p=0.087 for Instrumental Activities of Daily Living). The nutritional status improved over time (p=0.041). None of these three parameters at baseline, associated or not with ECOG and SORROR scores, impacted survivals or toxicities.

CONCLUSIONS: The cognitive, functional and nutritional status had no impact in this cohort of fit elderly AML patients without unfavorable cytogenetics. The GA tools used provided no additional information compared to ECOG and SORROR scores, to predict toxicity, morbidity, or mortality due to intensive chemotherapy.

PMID:33733520 | DOI:10.1111/ejh.13624

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Nevin Manimala Statistics

Transport of oxytocin to the brain after peripheral administration by membrane-bound or soluble forms of receptors for advanced glycation end-products

J Neuroendocrinol. 2021 Mar;33(3):e12963. doi: 10.1111/jne.12963.

ABSTRACT

Oxytocin (OT) is a neuropeptide hormone. Single and repetitive administration of OT increases social interaction and maternal behaviour in humans and mammals. Recently, it was found that the receptor for advanced glycation end-products (RAGE) is an OT-binding protein and plays a critical role in the uptake of OT to the brain after peripheral OT administration. Here, we address some unanswered questions on RAGE-dependent OT transport. First, we found that, after intranasal OT administration, the OT concentration increased in the extracellular space of the medial prefrontal cortex (mPFC) of wild-type male mice, as measured by push-pull microperfusion. No increase of OT in the mPFC was observed in RAGE knockout male mice. Second, in a reconstituted in vitro blood-brain barrier system, inclusion of the soluble form of RAGE (endogenous secretory RAGE [esRAGE]), an alternative splicing variant, in the luminal (blood) side had no effect on the transport of OT to the abluminal (brain) chamber. Third, OT concentrations in the cerebrospinal fluid after i.p. OT injection were slightly higher in male mice overexpressing esRAGE (esRAGE transgenic) compared to those in wild-type male mice, although this did not reach statistical significance. Although more extensive confirmation is necessary because of the small number of experiments in the present study, the reported data support the hypothesis that RAGE may be involved in the transport of OT to the mPFC from the circulation. These results suggest that the soluble form of RAGE in the plasma does not function as a decoy in vitro.

PMID:33733541 | DOI:10.1111/jne.12963

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Relationships between hope and mental health among women in prison

Crim Behav Ment Health. 2021 Mar 18. doi: 10.1002/cbm.2191. Online ahead of print.

ABSTRACT

BACKGROUND: Previous research with non-offenders has linked a higher dispositional cognition of hope to lower levels of psychological symptoms and demonstrated mediating effects of attentional biases on the relationship between hope and psychological symptoms, but this has not been explored among offenders.

AIMS: Our aim was to investigate associations between a dispositional cognition of hope and habitual attentional processing styles and distress among women in prison. We hypothesised that higher levels of hope would be associated with more attention to positive information and less to negative information in the surroundings and, in turn, lower levels of depression, anxiety and stress symptoms in women in prison.

METHOD: In a cross-sectional study, we recruited consenting women serving a prison sentence who had been referred to psychological services. Participants completed a set of self-rating inventories individually, which scaled their levels of hope, attention to positive and negative information and symptoms of anxiety, stress and depression.

RESULTS: Two hundred and three women participated. Their average age was 35.68 years (range 21-67 years). Over half were recidivists (170, 58%). Overall, the higher the level of hope they had, the lower were the ratings of their psychological symptoms. Positive attentional bias was associated with higher hope and lower psychological distress. In contrast, negative attentional bias was related to lower hope and higher psychological distress ratings. In statistical models, both attentional biases appeared to be partial mediators of the relationship between hope and psychological distress.

CONCLUSIONS: Our findings among women in prison were consistent with those in non-forensic populations and not previously studied among prisoners. They suggest that it would be worth evaluating interventions to modify attentional styles as they may have value in increasing hope and reducing psychological symptoms and perhaps also harmful behaviours in this vulnerable population.

PMID:33733563 | DOI:10.1002/cbm.2191

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Bipolar disorder and cannabis use: A bidirectional two-sample Mendelian randomization study

Addict Biol. 2021 Mar 17:e13030. doi: 10.1111/adb.13030. Online ahead of print.

ABSTRACT

Cannabis use is associated with a number of psychiatric disorders; however, the causal nature of these associations has been difficult to establish. Mendelian randomization (MR) offers a way to infer causality between exposures with known genetic predictors (genome-wide significant single nucleotide polymorphisms [SNPs]) and outcomes of interest. MR has previously been applied to investigate the relationship between lifetime cannabis use (having ever used cannabis) and schizophrenia, depression, and attention deficit hyperactivity disorder (ADHD), but not bipolar disorder, representing a gap in the literature. We conducted a two-sample bidirectional MR study on the relationship between bipolar disorder and lifetime cannabis use. Genetic instruments (SNPs) were obtained from the summary statistics of recent large genome-wide association studies (GWAS). We conducted a two-sample bidirectional MR study on the relationship between bipolar disorder and lifetime cannabis use using inverse variance weighted regression, weighted median regression, and Egger regression. Genetic liability to bipolar disorder was significantly associated with an increased risk of lifetime cannabis use; however, genetic liability to lifetime cannabis use showed no association with the risk of bipolar disorder. The sensitivity analyses showed no evidence for pleiotropic effects. The present findings support a causal effect of liability to bipolar disorder on the risk of using cannabis at least once. No evidence was found for a causal effect of liability to cannabis use on the risk of bipolar disorder. These findings add important new knowledge to the understanding of the complex relationship between cannabis use and psychiatric disorders.

PMID:33733564 | DOI:10.1111/adb.13030

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Nevin Manimala Statistics

Sample size re-estimation for covariate-adaptive randomized clinical trials

Stat Med. 2021 Mar 17. doi: 10.1002/sim.8939. Online ahead of print.

ABSTRACT

Covariate-adaptive randomization (CAR) procedures have been developed in clinical trials to mitigate the imbalance of treatments among covariates. In recent years, an increasing number of trials have started to use CAR for the advantages in statistical efficiency and enhancing credibility. At the same time, sample size re-estimation (SSR) has become a common technique in industry to reduce time and cost while maintaining a good probability of success. Despite the widespread popularity of combining CAR designs with SSR, few researchers have investigated this combination theoretically. More importantly, the existing statistical inference must be adjusted to protect the desired type I error rate when a model that omits some covariates is used. In this article, we give a framework for the application of SSR in CAR trials and study the underlying theoretical properties. We give the adjusted test statistic and derive the sample size calculation formula under the CAR setting. We can tackle the difficulties caused by the adaptive features in CAR and prove the asymptotic independence between stages. Numerical studies are conducted under multiple parameter settings and scenarios that are commonly encountered in practice. The results show that all advantages of CAR and SSR can be preserved and further improved in terms of power and sample size.

PMID:33733513 | DOI:10.1002/sim.8939

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First bite syndrome after parotidectomy: a single-centre experience

Int J Oral Maxillofac Surg. 2021 Mar 14:S0901-5027(21)00092-8. doi: 10.1016/j.ijom.2021.02.029. Online ahead of print.

ABSTRACT

The aim of this study was to investigate the prevalence of first bite syndrome (FBS) among post-parotidectomy patients and to analyse the risk factors for its occurrence. The study involved 111 adult patients operated for benign parotid tumours. After surgery, the participants were asked to assess the presence of food-related pain and the nature of the pain. Participants also answered questions on complications after parotidectomy. FBS was found in seven patients (6.3%). Sex (P=0.036) and age (P=0.002) differed significantly between patients with and without FBS. Female patients were found to be at higher risk of FBS, and the lower the patient’s age, the more likely FBS was to occur after surgery. Tumour location (P=0.002) and the occurrence of disturbing symptoms before surgery (P=0.009) had a statistically significant effect on the occurrence of FBS. A tendency towards significance for paresis of cranial nerve VII after surgery (P=0.051) was found; this complication was more frequent in the FBS patients. FBS is a rare pain syndrome that can occur after parotidectomy and should be distinguished from postoperative pain. Proper diagnosis and implementation of the appropriate treatment can significantly improve patient quality of life.

PMID:33731266 | DOI:10.1016/j.ijom.2021.02.029

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Nevin Manimala Statistics

Differentiation of Solid Pseudopapillary Tumor and Non-Functional Neuroendocrine Tumors of the Pancreas Based on CT Delayed Imaging: A Propensity Score Analysis

Acad Radiol. 2021 Mar 14:S1076-6332(21)00091-X. doi: 10.1016/j.acra.2021.02.020. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the diagnostic performance of the delayed-phase difference between tumor and pancreas for differentiating solid pseudopapillary tumors (SPTs) from non-functional neuroendocrine tumors (NF-NETs) of the pancreas.

METHODS: This retrospective review included 148 consecutive patients with SPT and 98 consecutive patients with NF-NET confirmed by pathology. Patients with SPT and NF-NET were matched via propensity score matching (PSM). All patients underwent multidetector computed tomography (MDCT). For each patient, the delayed-phase difference between the tumor and pancreas was measured, and the performance of this variable was assessed based on its discriminative ability and clinical utility.

RESULTS: After PSM, 27 patients with SPT and 27 patients with NF-NET were included in the matched analysis. There were no statistically significant differences in clinical and CT characteristics between the resulting two groups (p > 0.05). The delayed-phase difference values between the tumor and pancreas were significantly lower in patients with SPT (median: -0.45; range: -2.05 to 0.73) than in patients with NF-NET (median: 0.71; range: -1.39 to 2.38). The delayed-phase difference between tumor and pancreas had a high diagnostic accuracy (area under the curve=0.88). The best cutoff point based on maximizing the sum of the sensitivity and specificity was -0.23 (sensitivity = 88.89%; specificity = 88.89%; accuracy = 0.89).

CONCLUSIONS: The delayed-phase difference between tumor and pancreas can accurately and noninvasively differentiate SPT from NF-NET.

PMID:33731286 | DOI:10.1016/j.acra.2021.02.020

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Multicohort Retrospective Validation of a Predictive Biomarker for Topoisomerase I Inhibitors

Clin Colorectal Cancer. 2020 Dec 10:S1533-0028(20)30167-5. doi: 10.1016/j.clcc.2020.11.005. Online ahead of print.

ABSTRACT

PURPOSE: The camptothecin (CPT) analogs topotecan and irinotecan specifically target topoisomerase I (topoI) and are used to treat colorectal, gastric, and pancreatic cancer. Response rate for this class of drug varies from 10% to 30%, and there is no predictive biomarker for patient stratification by response. On the basis of our understanding of CPT drug resistance mechanisms, we developed an immunohistochemistry-based predictive test, P-topoI-Dx, to stratify the patient population into those who did and did not experience a response.

PATIENTS AND METHODS: The retrospective validation studies included a training set (n = 79) and a validation cohort (n = 27) of gastric cancer (GC) patients, and 8 cohorts of colorectal cancer (CRC) patient tissue (n = 176). Progression-free survival for 6 months was considered a positive response to CPT-based therapy. Formalin-fixed, paraffin-embedded slides were immunohistochemically stained with anti-phospho-specific topoI-Serine10 (topoI-pS10), quantitated, and analyzed statistically.

RESULTS: We determined a threshold of 35% positive staining to offer optimal test characteristics in GC. The GC (n = 79) training set demonstrated 76.6% (95% confidence interval, 64-86) sensitivity; 68.8% (41-88) specificity; positive predictive value (PPV) 92.5% (81-98); and negative predictive value (NPV) 42.3% (24-62). The GC validation set (n = 27) demonstrated 82.4% (56-95) sensitivity and 70.0% (35-92) specificity. Estimated PPV and NPV were 82.4% (56-95) and 70.0% (35-92) respectively. In the CRC validation set (n = 176), the 40% threshold demonstrated 87.5% (78-94) sensitivity; 70.0% (59-79) specificity; PPV 70.7% (61-79); and NPV 87.0 % (77-93).

CONCLUSION: The analysis of retrospective data from patients (n = 282) provides clinical validity to our P-topoI-Dx immunohistochemical test to identify patients with disease that is most likely to respond to topoI inhibitors.

PMID:33731288 | DOI:10.1016/j.clcc.2020.11.005

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Nevin Manimala Statistics

Migrating curlews on schedule: departure and arrival patterns of a long-distance migrant depend on time and breeding location rather than on wind conditions

Mov Ecol. 2021 Mar 17;9(1):9. doi: 10.1186/s40462-021-00252-y.

ABSTRACT

BACKGROUND: Departure decisions in long-distance migratory bird species may depend on favourable weather conditions and beneficial resources at the destination location, overarched by genetic triggers. However, few studies have tried to validate the significance of these three concepts simultaneously, and long-term, high-resolution tagging datasets recording individual movements across consecutive years are scarce. We used such a dataset to explore intraspecific and intra-individual variabilities in departure and arrival decisions from/to wintering grounds in relation to these three different concepts in bird migration.

METHODS: We equipped 23 curlews (Numenius arquata) wintering in the Wadden Sea with Global Positioning System data loggers to record their spatio-temporal patterns of departure from and arrival at their wintering site, and the first part of their spring migration. We obtained data for 42 migrations over 6 years, with 12 individuals performing repeat migrations in consecutive years. Day of year of departure and arrival was related to 38 meteorological and bird-related predictors using the least absolute shrinkage and selection operator (LASSO) to identify drivers of departure and arrival decisions.

RESULTS: Curlews migrated almost exclusively to Arctic and sub-Arctic Russia for breeding. They left their wintering site mainly during the evening from mid- to late April and returned between the end of June and mid-July. There was no difference in departure times between the sexes. Weather parameters did not impact departure decisions; if departure days coincided with headwind conditions, the birds accounted for this by flying at higher altitudes of up to several kilometres. Curlews breeding further away in areas with late snowmelt departed later. Departures dates varied by only < 4 days in individual curlews tagged over consecutive years.

CONCLUSIONS: These results suggest that the trigger for migration in this long-distance migrant is largely independent of weather conditions but is subject to resource availability in breeding areas. The high intra-individual repeatability of departure days among subsequent years and the lack of relationship to weather parameters suggest the importance of genetic triggers in prompting the start of migration. Further insights into the timing of migration in immatures and closely related birds might help to further unravel the genetic mechanisms triggering migration patterns.

PMID:33731224 | DOI:10.1186/s40462-021-00252-y