Quantile contours and allometric modelling for risk classification of abnormal ratios with an application to asymmetric growth-restriction in preterm infants

We develop an approach to risk classification based on quantile contours and allometric modelling of multivariate anthropometric measurements. We propose the definition of allometric direction tangent to the directional quantile envelope, which divides ratios of measurements into half-spaces. This in turn provides an operational definition of directional quantile that can be used as cutoff for risk assessment. We show the application of the proposed approach using a large dataset from the Vermont Oxford Network containing observations of birthweight (BW) and head circumference (HC) for more than 150,000 preterm infants. Our analysis suggests that disproportionately growth-restricted infants with a larger HC-to-BW ratio are at increased mortality risk as compared to proportionately growth-restricted infants. The role of maternal hypertension is also investigated.Comment: 31 pages, 3 figures, 8 table

Dimension reduction for longitudinal multivariate data by optimizing class separation of projected latent Markov models

We present a method for dimension reduction of multivariate longitudinal data, where new variables are assumed to follow a latent Markov model. New variables are obtained as linear combinations of the multivariate outcome as usual. Weights of each linear combination maximize a measure of separation of the latent intercepts, subject to orthogonality constraints. We evaluate our proposal in a simulation study and illustrate it using an EU-level data set on income and living conditions, where dimension reduction leads to an optimal scoring system for material deprivation. An R implementation of our approach can be downloaded from https://github.com/afarcome/LMdim

Testicular histopathology, semen analysis and FSH, predictive value of sperm retrieval: supportive counseling in case of reoperation after testicular sperm extraction (TESE)

Background: To provide indicators for the likelihood of sperm retrieval in patients undergoing testicular sperm extraction is a major issue in the management of male infertility by TESE. The aim of our study was to determine the impact of different parameters, including testicular histopathology, on sperm retrieval in case of reoperation in patients undergoing testicular sperm extraction. Methods: We retrospectively analyzed 486 patients who underwent sperm extraction for intracytoplasmic sperm injection and testicular biopsy. Histology was classified into: normal spermatogenesis; hypospermatogenesis (reduction in the number of normal spermatogenetic cells); maturation arrest (absence of the later stages of spermatogenesis); and Sertoli cell only (absence of germ cells). Semen analysis and serum FSH, LH and testosterone were measured. Results: Four hundred thirty patients had non obstructive azoospermia, 53 severe oligozoospermia and 3 necrozoospermia. There were 307 (63%) successful sperm retrieval. Higher testicular volume, lower levels of FSH, and better histological features were predictive for sperm retrieval. The same parameters and younger age were predictive factors for shorter time for sperm recovery. After multivariable analysis, younger age, better semen parameters, better histological features and lower values of FSH remained predictive for shorter time for sperm retrieval while better semen and histology remained predictive factors for successful sperm retrieval. The predictive capacity of a score obtained by summing the points assigned for selected predictors (1 point for Sertoli cell only, 0.33 points for azoospermia, 0.004 points for each FSH mIU/ml) gave an area under the ROC curve of 0.843. Conclusions: This model can help the practitioner with counseling infertile men by reliably predicting the chance of obtaining spermatozoa with testicular sperm extraction when a repeat attempt is planne

Hepatitis C virus eradication with directly acting antivirals improves health-related quality of life and psychological symptoms

BACKGROUND Alterations in health-related quality of life (HRQoL) and neuropsychological disorders were described in the hepatitis C virus (HCV) patients. Although several studies investigated the modifications of HRQoL after HCV eradication, no data exists on the modifications of neuropsychological symptoms. AIM To investigate the effect of directly acting antivirals (DAAs) treatment on HRQoL and neuropsychological symptoms. METHODS Thirty nine patients with HCV infection underwent a neuropsychological assessment, including Zung-Self Depression-Rating-Scale, Spielberg State-Trait Anxiety Inventory Y1-Y2 and the Toronto-Alexithymia Scale-20 items before and after DAAs treatment. HRQoL was detected by Short-Form-36 (SF-36). RESULTS All HRQoL domains, but role limitation physical and bodily pain, significantly improved after treatment. Interestingly, after DAAs treatment, all domains of HRQoL returned similar to those of controls. Each neuropsychological test significantly improved after HCV eradication. A significant correlation was observed among each psychological test and the summary components of SF-36. At multiple linear regression analysis including each psychological test as possible covariates, Zung-Self Depression Rating Scale (Zung-SDS) score was independently and significantly related to summary components of the SF-36 in the basal state and the difference between Zung-SDS score before and after treatment was the only variable significantly and independently related to the modification of HRQoL induced by the treatment. CONCLUSION Neuropsychological symptoms strongly influenced HRQoL in HCV patients and there was a significant improvement of neuropsychological tests and HRQoL after DAAs treatment

A study on serum calcium and phosphate in dialysis patients via a mixed effects latent markov model with two outcomes.

In pres

Investigating the effect of selective logging on tree biodiversity and structure of the tropical forests of Papua New Guinea

Abstract: Unsustainable exploitation of tropical forest resources is raising worldwide concern. In Papua New Guinea (PNG) timber harvesting has been identified as a major contributor to deforestation and forest degradation but its impact on biodiversity is still poorly understood. In this study we investigated the effect of selective logging on tree taxonomic composition, structure and diversity of PNG forests. We used data from 101 one-hectare permanent sample plots (PSPs) belonging to two vegetation types: low altitude forests on plains and fans (type P) and low altitude forests on uplands (type H). We used multivariate techniques to test for significant differences in species composition between plots of different vegetation types and disturbance regimes, identifying the tree taxa to which these differences could be ascribed. ANOVA was used to test for differences between logged-over and unlogged forest PSPs with respect to biodiversity (richness, Shannon's diversity, Pielou's evenness) and stand structure (stem density, basal area - BA). Temporal trends of forest features were analyzed using linear regression. Significant differences in taxonomic composition were found between logged-over and unlogged plots of the H type (p = 0.04). No differences were found in richness, diversity and evenness between logged-over and unlogged forest plots, while stem density was higher in the latter (421 ± 153 stems ha-1). Greater BA was found in unlogged forests (30.28 ± 4.45 m2 ha-1) of the H type when compared to the logged-over stands (15.52 ± 4.04 m2 ha-1). We detected positive trends in richness (0.55 ± 0.19 taxa ha-1 yr-1) and diversity after logging. Furthermore, H type forest exhibited positive trends in stem density (9 ± 1 stems ha-1 yr-1) and BA (0.42 ± 0.06 m2 ha-1 yr-1) with elapsed time since harvesting. Our analysis highlights some significant effects of logging activities on biodiversity and structure of PNG forests. Additionally, forests exhibited a significant recovery with respect to richness, diversity and stand structure. These preliminary results will be compared with data collected by the forthcoming National Forest Inventory in order to assess and monitor the effects of human activities and ecological factors on PNG forest biodiversity and develop appropriate conservation measures and sustainable management strategies

Role of PET gamma detection in radioguided surgery: a systematic review

Purpose This systematic review aimed to collect published studies concerning intraoperative gamma detection of positronemitting tracers for radioguided surgery (RGS) applications. Methods A systematic literature search of studies published until October 2022 was performed in Pubmed, Web Of Science, Central (Cochrane Library) and Scopus databases, including the following keywords: “Positron Emission Tomography” OR “PET” AND “Gamma” OR “γ” AND “Probe” AND “Radioguided Surgery” OR “RGS”. The included studies had to concern RGS procedures performed in at least 3 patients, regardless of the administered radiopharmaceutical and the field of application. Results Among to the 17 selected studies, all published between 2000 and 2022, only 2 investigations were conducted with gallium-68 (68Ga)-labeled somatostatin analogues, with fluorine-18-fluoro-2-deoxyglucose ([ 18F]FDG) being the most commonly used agent for RGS applications. Almost all studies were performed in oncologic patients, with only one paper also including inflammatory and infectious findings. The analysis showed that the largest part of procedures was performed through the intraoperative use of conventional gamma probes, not specifically designed for the detection of annihilation photons (n = 9), followed by PET gamma probes (n = 5) and with only three studies involving electronic collimation. Conclusions Regardless of the intraoperative devices, RGS with positron emitters seems to lead to significant improvements in surgeons’ ability to obtain a complete resection of tumors, even if the nature of photons resulting from positron–electron collision still remains extremely challenging and requires further technical advances

Monthly fluctuations in 25-hydroxy-vitamin D levels in day and rotating night shift hospital workers

Purpose Epidemiological studies have suggested that indoor hospital employees, either day or night shift workers, are at high risk of metabolic and cardiovascular diseases. Interestingly, previous reports have also described a higher prevalence of vitamin D (25OHD) deficiency among these workers. However, few studies have determined the monthly variations in 25OHD levels in indoor hospital employees. Methods To address this lack of knowledge, in 2018, during the periodic health surveillance checks at the Service of Occupational Medicine, we measured 25OHD levels in a group of indoor hospital workers (88 rotating night shift workers vs 200 day workers). Each participant received a single annual health surveillance check. Results The mean levels of 25OHD were consistently below the lower limit of the normal range in both groups throughout the year. Only in the summer, day workers but not rotating night shift workers (mean 25.9 +/- 11.3 ng/ml vs 23.1 +/- 9.1 ng/ml; p = 0.042) showed levels significantly higher than those in the other seasons. This difference remained statistically significant even after correction for study covariates [beta = - 1.649 (CI - 0.283/- 3.482), p = 0.039]. A cosinor analysis confirmed that the difference in the 25OHD levels between groups was present later in the year. Conclusions We found that relatively young healthy hospital workers, especially those with rotating night shifts, in the absence of significant metabolic risk factors, have a high risk of 25OHD deficiency/insufficiency. Because 25OHD deficiency may lead to a progression to more severe conditions such as osteoporosis or bone fractures, our results should be verified in larger cohorts including different ancestries

Highly predictive genetic markers distinguish drug-type from fiber-type cannabis sativa L

Genetic markers can be used in seeds and in plants to distinguish drug-type from fiber-type Cannabis Sativa L. varieties even at early stages, including pre-germination when cannabinoids are not accumulated yet. With this aim, this paper reports sequencing results for tetrahydrocannabinolic acid synthase (THCAS) and cannabidiolic acid synthase (CBDAS) genes from 21 C. sativa L. varieties. Taking into account that THCAS- and CBDAS-derived enzymes compete for the same substrate, the novelty of this work relies in the identification of markers based on bothTHCASandCBDASrather than THCAS alone. Notably, in our panel, we achieved an adequate degree of discrimination (AUC 100%) between drug-type and fiber-type cannabis samples. Our sequencing approach allowed identifying multiple genetic markers (single-nucleotide polymorphisms\u2014SNPs\u2014and a deletion/insertion) that effectively discriminate between the two subgroups of cannabis, namely fiber type vs. drug type. We identified four functional SNPs that are likely to induce decreased THCAS activity in the fiber-type cannabis plants. We also report the finding on a deletion in the CBDAS gene sequence that produces a truncated protein, possibly resulting in loss of function of the enzyme in the drug-type varieties. Chemical analyses for the actual concentration of cannabinoids confirmed the identification of drug-type rather than fiber-type genotypes. Genetic markers permit an early identification process for forensic applications while simplifying the procedures related to detection of therapeutic or industrial hemp

Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae

BACKGROUND: Bloodstream infections (BSIs) by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) are associated with high mortality. The aim of this study is to assess the relationship between time to administration of appropriate antibiotic therapy and the outcome of patients with BSI due to KPC-Kp hospitalized in intensive care unit (ICU). METHODS: An observational study was conducted in the ICUs of two academic centers in Italy. Patients with KPC-Kp bacteremia hospitalized between January 2015 to December 2018 were included. The primary outcome was the relationship between time from blood cultures (BC) collection to appropriate antibiotic therapy and 30-day mortality. The secondary outcome was to evaluate the association of different treatment regimens with 30-day mortality and a composite endpoint (30-day mortality or nephrotoxicity). A Cox regression analysis to identify factors independently associated with 30-day mortality was performed. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 102 patients with KPC-Kp BSI were included. The most common sources of infection were intra-abdominal (23.5%), urinary tract (20.6%), and skin and skin structure (17.6%). The 30-day mortality was 45%. Median time to appropriate antibiotic therapy was shorter in patients who survived (8.5\u2009h [IQR 1-36]) versus those who died (48\u2009h [IQR 5-108], p\u2009=\u20090.014). A propensity score matching showed that receipt of an in vitro active therapy within 24\u2009h from BC collection was associated with lower 30-day mortality (HR\u2009=\u20090.36, 95% CI: 0.188-0.690, p\u2009=\u20090.0021). At Cox regression analysis, factors associated with 30-day mortality were primary bacteremia (HR 2.662 [95% CI 1.118-6.336], p\u2009=\u20090.027), cardiovascular disease (HR 2.196 [95% CI 1.082-4.457], p\u2009=\u20090.029), time (24-h increments) from BC collection to appropriate therapy (HR 1.382 [95% CI 1.132-1.687], p\u2009=\u20090.001), SOFA score (HR 1.122 [95% CI 1.036-1.216], p\u2009=\u20090.005), and age (HR 1.030 [95% CI 1.006-1.054], p\u2009=\u20090.012). Ceftazidime-avibactam-containing regimens were associated with reduced risk of composite endpoint (30-day mortality OR nephrotoxicity) (HR 0.231 [95% CI 0.071-0.745], p\u2009=\u20090.014) compared to colistin-containing regimens. CONCLUSIONS: Time to appropriate antibiotic therapy is an independent predictor of 30-day mortality in patients with KPC-Kp BSI. Appropriate antibiotic therapy should begin within 24\u2009h from the collection of BC