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There are conflicting data about whether the development of cancer-associated thrombo-embolism (TE) negatively impacts survival in children. The objective was to determine whether TE during treatment was associated with overall survival (OS) and event-free survival (EFS) in children with acute lymphoblastic leukemia (ALL). We performed a population-based retrospective cohort study using the Cancer in Young People-Canada registry. Children less then 15 years of age were diagnosed with de novo ALL (2000-2016). The primary exposure variable was radiologically-confirmed thrombo-embolism requiring medical intervention. Multivariable Cox regression models were used to determine the impact of thrombo-embolism on survival, where TE was time-dependent. HS-173 in vitro We included 2006 children (median age 4 years, 88.5% precursor B-cell ALL). Thrombo-embolism occurred in 113 patients (5.6%), at a median time of 107 days (interquartile range 35-184 days) after ALL diagnosis. Among standard/low-risk patients, 41/1165 (3.5%) developed TE while among high/very high-risk patients, 72/841 (8.6%) developed TE. Patients with TE had a significantly worse OS (adjusted HR [aHR] of death 2.61, 95% CI 1.62-4.22, p less then 0.001) and EFS (aHR of an event [death, relapse, second malignancy] 2.03, 95% CI 1.35-3.05, p = 0.001), compared with patients without TE. No statistically significant difference was seen in standard/low risk ALL for OS and EFS, but TE was associated with a significantly lower OS and EFS in children with high/very high-risk ALL (aHR of death 2.90, 95% CI 1.79-4.72, p less then 0.001; aHR of an event 2.02, 95% CI 1.30-3.12, p = 0.002). Thus, TE led to a statistically significant reduction in OS and EFS in children with high risk/very high-risk leukemia.
Donor demise after laser surgery for twin-twin transfusion syndrome (TTTS) is well-characterized, but recipient demise is not, nor is neonatal death. This study aims to characterize factors associated with recipient death, donor death, and dual twin death after laser, both before and after birth.
This is a prospective cohort study of monochorionic twin pairs who underwent laser ablation for TTTS. Risk factors for fetal and neonatal death of both twins were identified using univariable analysis and recursive partitioning, a novel statistical method to quantify contributions of each factor to outcomes.
In 413 twin pairs, death of both twins occurred in 9.2% (38/413), donor death in 12.1% (50/413), and recipient death in 2.4% (10/413). Recursive partitioning showed that gestational age at delivery predicts dual twin death (below 23.7 weeks, likely [p<0.001], above 28.3weeks, unlikely [p=0.004]). Abnormal umbilical artery Doppler and weight discordance predict donor demise (p<0.001 and p=0.033, respectively). Cervical length under 16mm predicts neonatal death of both twins (p<0.001).
Parents can gain individualized information about the survival of each fetus based on variables available from preoperative and delivery variables. Short cervix and premature delivery cause significant mortality in TTTS.
Parents can gain individualized information about the survival of each fetus based on variables available from preoperative and delivery variables. Short cervix and premature delivery cause significant mortality in TTTS.
The first objective of this study was to apply computer vision and machine learning techniques to quantify the effects of haircare treatments on hair assembly and to identify correctly whether unknown tresses were treated or not. The second objective was to explore and compare the performance of human assessment with that obtained from artificial intelligence (AI) algorithms.
Machine learning was applied to a data set of hair tress images (virgin and bleached), both untreated and treated with a shampoo and conditioner set, aimed at increasing hair volume whilst improving alignment and reducing the flyway of the hair. The automatic quantification of the following hair image features was conducted local and global hair volumes and hair alignment. These features were assessed at three time points t
(no treatment), t
(two treatments) and t
(three treatments). Classifier tests were applied to test the accuracy of the machine learning. A sensory test (paired comparison of t
vs t
) and an online front classification, and for image analysis of hair assembly features following treatments. The human assessment partially confirmed the image analysis and highlighted the challenges imposed by the presentation mode.
This study illustrated the capacity of artificial intelligence for hair image detection and classification, and for image analysis of hair assembly features following treatments. The human assessment partially confirmed the image analysis and highlighted the challenges imposed by the presentation mode.Dopamine signaling in nucleus accumbens (NAc) is modulated by γ-aminobutyric acid (GABA), acting through GABA-A and GABA-B receptors dysregulation of GABAergic control of dopamine function may be important in behavioral deficits in schizophrenia. We investigated the effect of GABA-A (muscimol) and GABA-B (baclofen) receptor agonists on electrically stimulated dopamine release. Furthermore, we explored whether drug-induced changes were disrupted by pretreatment with phencyclidine, which provides a well-validated model of schizophrenia. Using brain slices from female rats, fast-scan cyclic voltammetry was used to measure electrically stimulated dopamine release in NAc shell. Both muscimol and baclofen caused concentration-dependent attenuation of evoked dopamine release neither effect was changed by dihydro-β-erythroidine, a nicotinic acetylcholine receptor antagonist, or the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), precluding indirect mechanisms using these transmitter systems in the GABAergic actions. In slices taken from rats pretreated with phencyclidine, the attenuation of evoked dopamine release by baclofen was abolished, but the attenuation by muscimol was unaffected. Since phencyclidine pretreatment was followed by drug-free washout period of at least a week, the drug was not present during recording. Therefore, disruption of GABA-B modulation of dopamine is due to long-term functional changes resulting from the treatment, rather than transient changes due to the drug's presence at test. This enduring dysregulation of GABA-B modulation of accumbal dopamine release provides a plausible mechanism through which GABA dysfunction influences accumbal dopamine leading to behavioral changes seen in schizophrenia and may provide a route for novel therapeutic strategies to treat the condition.Hereditary xerocytosis is a rare red blood cell disease related to gain-of-function mutations in the FAM38A gene, encoding PIEZO1, in 90% of cases; PIEZO1 is a broadly expressed mechano-transducer that plays a major role in many cell systems and tissues that respond to mechanical stress. In erythrocytes, PIEZO1 adapts the intracellular ionic content and cell hydration status to the mechanical constraints induced by the environment. Until recently, the pathophysiology of hereditary xerocytosis was mainly believed to be based on the "PIEZO1-Gardos channel axis" in erythrocytes, according to which PIEZO1-activating mutations induce a calcium influx that secondarily activates the Gardos channel, leading to potassium and water efflux and subsequently to red blood cell dehydration. However, recent studies have demonstrated additional roles for PIEZO1 during early erythropoiesis and reticulocyte maturation, as well as roles in other tissues and cells such as lymphatic vessels, hepatocytes, macrophages and platelets that may affect the pathophysiology of the disease. These findings, presented and discussed in this review, broaden our understanding of hereditary xerocytosis beyond that of primarily being a red blood cell disease and identify potential therapeutic targets.
The value of chromosome microarray (CMA) in the prenatal detection of significant chromosome anomalies is well-established. To guide the introduction of this technique in routine clinical practice, the Joint Committee on Genomics in Medicine developed national UK guidelines for reporting prenatal CMA in 2015.
To evaluate the UK experience of utilising prenatal CMA.
A 36-item survey was distributed to all UK clinical genetics services (n=23) in March 2019 requesting information pertaining to experience since diagnostic testing commenced and current practice (March 2018 to March 2019).
Eighteen UK genetics services currently offer prenatal CMA. A total of 14,554 tests had been performed. A pathogenic copy number variant was identified in 7.8% of tests overall, though the diagnostic rate increased to 8.4% in the final year of the survey. Variants of uncertain significance (VUS) were reported in 0.7% of tests, and 'actionable' incidental findings in 0.12%.
Diagnostic rate has improved over time, while reporting of VUS has decreased. Reviewing survey responses at a national level highlights variation in testing experience and practice, raising considerations both for future guideline development and implementation of other novel techniques including prenatal whole exome sequencing.
Diagnostic rate has improved over time, while reporting of VUS has decreased. Reviewing survey responses at a national level highlights variation in testing experience and practice, raising considerations both for future guideline development and implementation of other novel techniques including prenatal whole exome sequencing.Vancouver Island marmots (Marmota vancouverensis) have been managed in a captive-breeding program since 1997, as in situ conservation efforts were insufficient in raising the numbers of this critically endangered species. The success of captive-breeding programs centers on sustainable reproduction and survival of individuals once released into the wild. Captive-born Vancouver Island marmots released to the wild have lower survival rates than their wild-born counterparts; this difference may arise from compromised hibernation patterns or behaviors. Hibernation duration, body weight over the hibernation season, and reproductive success of captive Vancouver Island marmots were reviewed to assess the effect of these variables on each other. Data from a total of 1782 hibernations and 456 breeding attempts were compiled from 1997 to 2018. The number of winters spent in captivity, the origin of the marmot (captive-born or wild-born), the facility at which hibernation occurred, and the body weight all had a significant effect on hibernation length (all p less then .001). Increased weight was associated with increased hibernation length by 0.4 ± 0.1 day/kg on average (p = .0015). Captive, wild-born marmots hibernated for significantly longer than their captive-born counterparts by about 21 ± 2 days (p less then .001). The odds of successful breeding were significantly increased with increasing hibernation length by approximatively 20% for every 10 additional days of hibernation. This study provides information on the intrinsic relationship between body weight, reproduction, and hibernation in captive Vancouver Island marmots.
