Tag: nevin manimala

Acta Neurochir (Wien). 2023 Sep 11. doi: 10.1007/s00701-023-05780-7. Online ahead of print.

ABSTRACT

BACKGROUND: Elective use of intraparenchymal intracranial pressure (ICP) monitoring is a valuable resource in the investigation of hydrocephalus and other cerebrospinal fluid disorders. Our preliminary study aims to investigate ICP changes in the immediate period following dural breach, which has not yet been reported on.

METHOD: This is a prospective cohort study of patients undergoing elective ICP monitoring, recruited between March and May 2022. ICP readings were obtained at opening and then at 5-min intervals for a 30-min duration.

RESULTS: Ten patients were recruited, mean age 45 years, with indications of a Chiari malformation (n = 5), idiopathic intracranial hypertension (n = 3) or other ICP-related pathology (n = 2). Patients received intermittent bolus sedation (80%) vs general anaesthesia (20%). Mean opening pressure was 22.9 mmHg [± 6.0], with statistically significant decreases present every 5 min, to a total reduction of 15.2 mmHg at 20 min (p = < 0.0001), whereafter the ICP plateaued with no further statistical change.

DISCUSSION: Our results highlight an intracranial opening pressure ‘spike’ phenomenon. This spike was 15.2 mmHg higher than the plateau, which is reached at 20 min after insertion. Several possible causes exist which require further research in larger cohorts, including sedation and pain response. Regardless of causation, this study provides key information on the use of ICP monitoring devices, guiding interpretation and when to obtain measurements.

PMID:37695437 | DOI:10.1007/s00701-023-05780-7

Drugs. 2023 Sep 11. doi: 10.1007/s40265-023-01936-y. Online ahead of print.

ABSTRACT

BACKGROUND: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has changed in recent years with the approval of new antiseizure medications (ASMs).

OBJECTIVE: The aim of this study was to estimate the comparative efficacy and tolerability of the ASMs for the treatment of seizures associated with DS using a network meta-analysis (NMA).

METHODS: Studies were identified by conducting a systematic search (week 4, January 2023) of the MEDLINE (accessed by PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and US National Institutes of Health Clinical Trials Registry ( http://www.

CLINICALTRIALS: gov ) databases. Any randomized, controlled, double- or single-blinded, parallel-group study comparing at least one ASM therapy against placebo, another ASM, or a different dose of the same ASM in participants with a diagnosis of DS was identified. The efficacy outcomes were the proportions of participants with ≥ 50% (seizure response) and 100% reduction (seizure freedom) in baseline convulsive seizure frequency during the maintenance period. The tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and who experienced at least one adverse event (AE). Effect sizes were estimated by network meta-analyses within a frequentist framework.

RESULTS: Eight placebo-controlled trials were included, and the active add-on treatments were stiripentol (n = 2), pharmaceutical-grade cannabidiol (n = 3), fenfluramine hydrochloride (n = 2), and soticlestat (n = 1). The studies recruited 680 participants, of whom 409 were randomized to active treatments (stiripentol = 33, pharmaceutical-grade cannabidiol = 228, fenfluramine hydrochloride = 122, and soticlestat = 26) and 271 to placebo. Pharmaceutical-grade cannabidiol was associated with a lower rate of seizure response than fenfluramine hydrochloride (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.07-0.54), and stiripentol was associated with a higher seizure response rate than pharmaceutical-grade cannabidiol (OR 14.07, 95% CI 2.57-76.87). No statistically significant differences emerged across the different ASMs for the seizure freedom outcome. Stiripentol was associated with a lower probability of drug discontinuation for any reason than pharmaceutical-grade cannabidiol (OR 0.45, 95% CI 0.04-5.69), and pharmaceutical-grade cannabidiol was associated with a lower proportion of participants experiencing any AE than fenfluramine hydrochloride (OR 0.22, 95% CI 0.06-0.78). Stiripentol had a higher risk of AE occurrence than pharmaceutical-grade cannabidiol (OR 75.72, 95% CI 3.59-1598.58). The study found high-quality evidence of efficacy and tolerability of the four ASMs in the treatment of convulsive seizures in DS.

CONCLUSIONS: There exists first-class evidence that documents the efficacy and tolerability of stiripentol, pharmaceutical-grade cannabidiol, fenfluramine hydrochloride, and soticlestat for the treatment of seizures associated with DS, and allows discussion about the expected outcomes regarding seizure frequency reduction and tolerability profiles.

PMID:37695433 | DOI:10.1007/s40265-023-01936-y

Psychol Trauma. 2023 Sep 11. doi: 10.1037/tra0001581. Online ahead of print.

ABSTRACT

OBJECTIVE: Global emotion dysregulation mediates the relationship between child maltreatment and severe depressive symptoms; however, there is a lack of research on maladaptive personality traits and their contribution to individual differences in global emotion dysregulation within this conceptual model. The present study tested a preliminary serial mediation model where maladaptive personality traits and global emotion dysregulation mediate the relationship between child maltreatment and severe depressive symptoms.

METHOD: A total of 200 patients with mood disorders (M_age = 36.5 years; 54% females) were assessed for maladaptive personality traits (Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders [5th ed.] Brief Form), global emotion dysregulation (Difficulties in Emotion Regulation Scale-Short), childhood trauma (Childhood Trauma Questionnaire), and depressive symptoms (Patient Health Questionnaire-9).

RESULTS: Ordinary least squares regression and partial least squares-structural equation modeling revealed a consistent and significant indirect effect of child maltreatment on severe depressive symptoms through negative affectivity, detachment, psychoticism, and global emotion dysregulation. Among child maltreatment types, only emotional abuse had a significant indirect effect on severe depressive symptoms through maladaptive personality traits and global emotion dysregulation, b = 0.50, SE = 0.09, 95% confidence intervals [0.326, 0.694] after controlling for age, gender, and remaining types of child maltreatment.

CONCLUSIONS: Findings support the view that maladaptive personality traits shed important insights on individual differences in global emotion dysregulation, and this information could aid clinical formulation and treatment of childhood adversity-related psychopathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PMID:37695361 | DOI:10.1037/tra0001581

J Exp Psychol Gen. 2023 Sep 11. doi: 10.1037/xge0001440. Online ahead of print.

ABSTRACT

Humans are particularly sensitive to relationships between parts of objects. It remains unclear why this is. One hypothesis is that relational features are highly diagnostic of object categories and emerge as a result of learning to classify objects. We tested this by analyzing the internal representations of supervised convolutional neural networks (CNNs) trained to classify large sets of objects. We found that CNNs do not show the same sensitivity to relational changes as previously observed for human participants. Furthermore, when we precisely controlled the deformations to objects, human behavior was best predicted by the number of relational changes while CNNs were equally sensitive to all changes. Even changing the statistics of the learning environment by making relations uniquely diagnostic did not make networks more sensitive to relations in general. Our results show that learning to classify objects is not sufficient for the emergence of human shape representations. Instead, these results suggest that humans are selectively sensitive to relational changes because they build representations of distal objects from their retinal images and interpret relational changes as changes to these distal objects. This inferential process makes human shape representations qualitatively different from those of artificial neural networks optimized to perform image classification. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PMID:37695326 | DOI:10.1037/xge0001440

Syst Biol. 2023 Sep 11:syad057. doi: 10.1093/sysbio/syad057. Online ahead of print.

ABSTRACT

The popularity of relaxed clock Bayesian inference of clade origin timings has generated several recent publications with focal results considerably older than the fossils of the clades in question. Here we critically examine two such clades: the animals (with focus on the bilaterians); and the mammals (with focus on the placentals). Each example displays a set of characteristic pathologies which, although much commented on, are rarely corrected for. We conclude that in neither case does the molecular clock analysis provide any evidence for an origin of the clade deeper than what is suggested by the fossil record. In addition, both these clades have other features (including, in the case of the placental mammals, proximity to a large mass extinction) that allow us to generate precise expectations of the timings of their origins. Thus, in these instances the fossil record can provide a powerful test of molecular clock methodology, and why it goes astray; and we have every reason to think these problems are general.

PMID:37695319 | DOI:10.1093/sysbio/syad057

J Manag Care Spec Pharm. 2023 Sep 11:1-12. doi: 10.18553/jmcp.2023.23045. Online ahead of print.

ABSTRACT

BACKGROUND: Research conducted in 2017 by Runyan et al concerning the current and future management of oncology drugs in the United States formed the basis for this research. The authors concluded that despite the high cost of oncology drugs, US payers relied on traditional management tools to manage the category, although these tools were ineffective at controlling costs. Innovative tools were not common in 2017. OBJECTIVE: To compare findings from the 2017 research with findings from a 2022 payer survey to understand how payer management of oncology drugs changed over 5 years. The study evaluates changing trends in oncology drug management. METHODS: The survey that informed the publication by Runyan et al in 2017 was reviewed, updated, and completed by 21 pharmacy and medical directors across 18 organizations representing 121.9 million covered lives. Both surveys included questions about management tools being employed in oncology and challenges to managing oncology. They used case studies in non-small cell lung cancer and chronic lymphocytic leukemia. These disease areas were chosen again in 2022 because they were included in the 2017 survey and because of the increase in competition in both categories from 2017 to 2022. The payer sample was designed to match the 2017 sample. The research was fielded from March to May 2022. The results were analyzed in Microsoft Excel; basic statistical analysis was conducted. Payers’ responses for each question were weighted by the number of reported covered lives at their organization so that the organization’s site was represented. RESULTS: On average, payers rated the management priority of oncology as a 5.3 and the budget impact as a 6.3 on a scale of 1 to 7, where 1 was low and 7 was high. Traditional tools remain dominant in this therapeutic area. However, there has been an increase in use of innovative tools. Pathways of care are trending upward since the initial survey in 2017. The Institute for Clinical and Economic Review (ICER) also influences payers’ decision-making in oncology more than it did 5 years ago. Despite these shifts, most payers allow for unrestricted access of targeted therapies in non-small cell lung cancer and chronic lymphocytic leukemia, in line with each drug’s US Food and Drug Administration-approved label. CONCLUSIONS: The increased use of pathways of care, shifting financial risk to providers, and the influence of ICER should continue to be monitored. Future research should focus on the role of pathways of care, comprehensive, evidence-based treatment protocols, in influencing prescribing decisions of hematologists and oncologists. DISCLOSURES: The authors work for Envision Pharma Group (formerly Two Labs), a company that provides consulting services to the pharmaceutical and biotech industries. As such, clients in these industries pay Envision Pharma Group for their services. This study was funded independently by Envision Pharma Group.

PMID:37695273 | DOI:10.18553/jmcp.2023.23045

Sci Total Environ. 2023 Sep 8:166915. doi: 10.1016/j.scitotenv.2023.166915. Online ahead of print.

ABSTRACT

Ground hardening in urban areas increases the risk of thermal enrichment in surface rainwater runoff. Moreover, the thermal pollution from rainwater runoff has become an important problem that damages the urban aquatic environment. Current studies have focused mainly on the potential hazard caused by runoff thermal pollution to aquatic microorganisms. However, there are few studies on the efficacy of controlling runoff thermal load through low-impact development (LID) and renovation in urban areas. The effects of LID modification were evaluated by monitoring the characteristics of the runoff thermal load on each underlying surface in the study area and conducting laboratory-scale bioretention experiments. The results showed that the initial thermal effect of each underlying surface was significant after the start of rainfall, based on the thermal load. Ceramic granules are remarkable bioretention fillers. Their average heat load and volume reduction rates are 55.6 % and 32.7 %, respectively. After LID modification, the thermal load of surface runoff in the study area decreased to 73.42 % under similar rainfall conditions. After the secondary treatment of the bioretention facility, the total thermal load of the outflow facility was 31.40 % of that before renovation. The peak thermal load reduced by 69.15 % and was delayed for 10 min. The control effect differed statistically.

PMID:37690765 | DOI:10.1016/j.scitotenv.2023.166915

Chem Biol Interact. 2023 Sep 8:110699. doi: 10.1016/j.cbi.2023.110699. Online ahead of print.

ABSTRACT

Parabens have been used for decades as preservatives in food, drugs and cosmetics. The majority however, were banned in 2009 and 2014 leaving only methyl-, ethyl-, propyl-, and butyl-derivates available for subsequent use. Methyl- and propylparaben have been extensively tested in vivo, with no resulting evidence for developmental and reproductive toxicity (DART). In contrast, ethylparaben has not yet been tested for DART in animal experiments, and it is currently debated if additional animal studies are warranted. In order to perform a comparison of the four currently approved parabens, we used a previously established in vitro test based on human induced pluripotent stem cells (iPSC) that are exposed to test substances during their differentiation to neuroectodermal cells. EC₅₀ values for cytotoxicity were 906 μM, 698 μM, 216 μM and 63 μM for methyl-, ethyl-, propyl- and butylparaben, respectively, demonstrating that cytotoxicity increases with increasing alkyl chain length. Genome-wide analysis demonstrated that FDR-adjusted significant gene expression changes occurred only at cytotoxic or close to cytotoxic concentrations, for example 1720 differentially expressed genes (DEG) at 1000 μM ethylparaben, 1 DEG at 316 μM, and no DEG at 100 μM or lower concentrations. The highest concentration of ethylparaben that did not induce any cytotoxicity nor DEG was 1670-fold above the highest published concentrations reported in biomonitoring studies (60 nM ethylparaben in cord blood). In conclusion, cytotoxicity and gene expression alterations of ethylparaben occurred at concentrations of approximately three orders of magnitude above human blood concentrations; moreover, the substance fitted well into a scenario where toxicity increases with the alkyl chain length, and gene expression changes only occur at cytotoxic or close to cytotoxic concentrations. Therefore, no evidence was obtained suggesting that in vivo DART with ethylparaben would lead to different results as the methyl- or propyl derivates.

PMID:37690743 | DOI:10.1016/j.cbi.2023.110699

J Dairy Sci. 2023 Sep 8:S0022-0302(23)00626-4. doi: 10.3168/jds.2023-23478. Online ahead of print.

ABSTRACT

A 305-d lactation followed by a 60-d dry period has traditionally been considered economically optimal, yet dairy cows in modern intensive dairy systems are frequently dried off while still producing significant quantities of milk. Managing cows for an extended lactation has reported production, welfare and economic benefits, but not all cows are suitable for an extended lactation. Implementation of an extended lactation strategy on-farm could benefit from use of a decision support system, based on a mathematical lactation model, that can identify suitable cows during early lactation that have a high likelihood of producing above a target milk yield (MY) at 305 d in milk (DIM). Therefore, our objectives were 1) to compare the suitability of 3 commonly used lactation models for modeling extended lactations (Dijkstra, Wood, and Wilmink) in primiparous and multiparous cows under a variety of lactation lengths, and 2) to determine the amount of early lactation daily MY data needed to accurately forecast MY at d 305 by using the most suitable model and determine if this is sufficient for identifying cows suitable for an extended lactation before the end of a typical voluntary waiting period (50 to 90 d). Daily MY data from 467 individual Holstein-Friesian lactations (DIM >305 d; 379 ± 65 d lactation length [mean ± SD]) were fitted by the 3 lactation models using a nonlinear regression procedure. The parameter estimates of these models, lactation characteristics (peak yield, time to peak yield, and persistency), and goodness-of-fit were compared between parity and different lactation lengths. The models had similar performance and differences between parity groups were consistent with previous literature. Then, data from only the first i DIM for each individual lactation, where i was incremented by 30 d from 30 to 150 DIM and by 50 d from 150 to 300 DIM, were fitted by each model to forecast MY at d 305. The Dijkstra model was selected for further analysis as it had superior goodness-of-fit statistics for i = 30 and 60. The data set was fit twice by the Dijkstra model, with parameter bounds either unconstrained or constrained. The quality of predictions of MY at d 305 improved with increasing data availability for both models and assisting the model fitting procedure with more biologically relevant constraints on parameters improved the predictions, but neither was reliable enough for practical use on-farm due to the high uncertainty of forecasted predictions. Using 90 d of data, the constrained model correctly classified 66% of lactations as being above or below a target MY at d 305 of 25 kg/d, with a probability threshold of 0.95. The proportion of correct classifications became smaller at lower targets of MY at d 305 and became greater when using more lactation days. Overall, further work is required to develop a model that can forecast late lactation MY with sufficient accuracy for practical use. We envisage that a hybridized machine learning and mechanistic model that incorporates additional historical and genetic information with early lactation MY could produce meaningful lactation curve forecasts.

PMID:37690727 | DOI:10.3168/jds.2023-23478

J Dairy Sci. 2023 Sep 8:S0022-0302(23)00641-0. doi: 10.3168/jds.2023-23874. Online ahead of print.

ABSTRACT

We determined the effects of altering the ratio of palmitic (C16:0) and stearic (C18:0) acids in supplemental fatty acid (FA) blends on production responses of mid-lactation dairy cows. Twenty-four multiparous Holstein cows (mean ± standard deviation; 47.1 ± 5.8 kg of milk yield, 109 ± 23 DIM) were randomly assigned to treatment sequences in a replicated 4 × 4 Latin square design with 21-d periods. Treatments were a non-FA supplemented control diet (CON), and 3 diets incorporating 1.5% dry matter (DM) FA supplement blends containing 30% C16:0 + 50% C18:0 (L-PA), 50% C16:0 + 30% C18:0 (M-PA), and 80% C16:0 + 10% C18:0 (H-PA). Additionally, the FA blends were balanced to contain 10% oleic acid (cis-9 C18:1). The FA blends replaced soyhulls in the CON diet. Diets were formulated to contain (% DM) 31.0% neutral detergent fiber, 27.0% starch, and 16.9% crude protein. The statistical model included the random effect of cow within square and the fixed effects of period, treatment, and their interaction. Pre-planned contrasts included CON vs. overall effect of FA supplementation (FAT) and the linear and quadratic effects of increasing C16:0 in FA blends. Overall FAT had no effect on dry matter intake but increasing C16:0 linearly increased dry matter intake. Compared with CON, overall FAT increased yields of milk, 3.5% fat corrected milk, energy corrected milk, and milk fat, but did not affect milk protein yield. Increasing C16:0 linearly increased milk fat yield and tended to linearly increase the yields of 3.5% fat corrected milk and energy corrected milk. FAT decreased the yield of de novo milk FA, but increased yields of mixed and preformed milk FA compared with CON. Increasing C16:0 in FA treatments did not affect the yield of de novo milk FA, linearly increased the yield of mixed and decreased the yield of preformed milk FA. In summary, feeding FA supplements containing C16:0 and C18:0 increased milk production responses with no effect on DMI compared with a non-FA supplemented control diet. Mid-lactation cows producing ∼40-50 kg/d of milk yield responded best to increasing supplemental C16:0 in FA supplements, demonstrating that FA supplements higher in C16:0, and limiting C18:0, improves production responses.

PMID:37690714 | DOI:10.3168/jds.2023-23874