The Effects of Alcohol and Traumatic Brain Injury on Neural Stem Cell Responses

Traumatic brain injury (TBI) is a major source of disability in modern societies. However, there are no good pharmacological strategies for treating long-term TBI complications because we do not fully understand the injury processes that occur afterward. Moreover, a significant percent of patients entering the emergency room with TBI have a blood alcohol level above the legal limit. Alcohol use and intoxication is a widespread issue in our society. Binge drinking is the most common way in which alcohol is consumed, and alarmingly, Americans of all age groups binge drink on a frequent basis. Despite the prevalence of alcohol intoxication seen together with TBI, how it affects the brain injury and recovery process is not well understood. Our laboratory has previously found that a repeated dose of binge alcohol prior to TBI impairs functional sensorimotor recovery. One means by which the brain responds to injury is the mobilization of neural precursor cells produced by neurogenesis. However, the effect of pre-injury binge alcohol exposure on the reactive neurogenesis that occurs after TBI is not known. Adult neurogenesis is an alternative form of plasticity, which involves the production of new neurons and may contribute to functional recovery after TBI. The subventricular zone (SVZ) is one of the brain’s main neurogenic niches. The experiments in this dissertation therefore sought to determine the short and long term effects of pre-TBI binge alcohol on the neural stem cell responses in the SVZ following brain injury. We assessed the SVZ neural stem cell response after binge alcohol and TBI by utilizing the proliferation marker 5-bromo-2’-deoxyuridine (BrdU) along with other markers for neurogenesis such as Doublecortin. We found that binge alcohol did not affect short and long term lesion size (as measured at 24 hours, 7 days and 6 weeks post TBI). As expected, TBI alone significantly increased SVZ proliferation bilaterally 24 hours post injury. Surprisingly, binge alcohol alone also significantly increased proliferation bilaterally in the SVZ at the 24 hour time point. A combined binge alcohol and TBI regimen resulted in decreased SVZ proliferation bilaterally at 24 hours and 7 days post-TBI. Furthermore, when assessed at 6 weeks after TBI, binge alcohol significantly decreased SVZ neuronal differentiation. While we observed that TBI alone increased migration toward the rostral migratory stream (RMS), binge alcohol did not affect either RMS or perilesional migration post-TBI. Taken together, the results from this dissertation suggest that pre-TBI binge alcohol negatively impacts functional recovery by decreasing short-term neural stem cell proliferative responses as well as long-term neuronal differentiation of these proliferative cells in the SVZ

Does recreational drug use influence survival and morbidity associated with laryngeal cancer

Background: The use of opioids is considered a risk factor for laryngeal cancer. A retrospective study was performed to explore the relationship between recreational drug exposure and laryngeal cancer.Methods: Patients diagnosed between the 1st of January 2013 and the 31st of December 2017 using ICD-10 CD-32 coding were identified from the Head and Neck Multidisciplinary Team database. We divided the study population into two cohorts (RD and non-RD) and compared the demographics, morbidity, and outcomes of these two populations. In addition, we performed case-matched analysis to control for potential confounding factors including gender, alcohol use and cigarette smoking.Findings: 329 patients in Glasgow, Scotland were included with a mean age of 64.96 ± 10.94 and a follow-up of 24 ± 13.91 months. Of these, 39 reported recreational drug use (RD). RD was associated with younger age (53.0 vs. 66.6, p<0.001) at diagnosis with laryngeal cancer. A greater proportion of tumours occurred in the supraglottic subsite (p=0.041). Furthermore, these patients were more likely to undergo tracheostomy (RR=2.50, 95% CI: 1.41-4.44, p=0.008) and laryngectomy (RR=2.25, 95% CI: 1.57-3.21, p<0.001). Recreational drug users were more likely to require enteral feeding support (RR= 1.44, 95% CI: 1.13-1.84, p=0.02) during oncological treatment. No survival differences were noted at 1, 2, or 3-years (plog-rank=0.83). Case matched analysis correcting for smoking, alcohol and gender confirmed that recreational drug users were younger at diagnosis with a predilection for the supraglottic subsite.Conclusion: Recreational drug use is associated with an increased burden of disease and morbidity in laryngeal cancer. We suggest that clinicians view recreational drug exposure as a red flag in those with suspected laryngeal cancer regardless of patient age

SL-COMP: Competition of Solvers for Separation Logic

International audienceSL-COMP aims at bringing together researchers interested on improving the state of the art of the automated deduction methods for Separation Logic (SL). The event took place twice until now and collected more than 1K problems for different fragments of SL. The input format of problems is based on the SMT-LIB format and therefore fully typed; only one new command is added to SMT-LIB's list, the command for the declaration of the heap's type. The SMT-LIB theory of SL comes with ten logics, some of them being combinations of SL with linear arithmetics. The competition's divisions are defined by the logic fragment, the kind of decision problem (satisfiability or entailment) and the presence of quantifiers. Until now, SL-COMP has been run on the StarExec platform, where the benchmark set and the binaries of participant solvers are freely available. The benchmark set is also available with the competition's documentation on a public repository in GitHub

Evaluation of Luminex xTAG Gastrointestinal Pathogen Panel Assay for Detection of Multiple Diarrheal Pathogens in Fecal Samples in Vietnam.

Diarrheal disease is a complex syndrome that remains a leading cause of global childhood morbidity and mortality. The diagnosis of enteric pathogens in a timely and precise manner is important for making treatment decisions and informing public health policy, but accurate diagnosis is a major challenge in industrializing countries. Multiplex molecular diagnostic techniques may represent a significant improvement over classical approaches. We evaluated the Luminex xTAG gastrointestinal pathogen panel (GPP) assay for the detection of common enteric bacterial and viral pathogens in Vietnam. Microbiological culture and real-time PCR were used as gold standards. The tests were performed on 479 stool samples collected from people admitted to the hospital for diarrheal disease throughout Vietnam. Sensitivity and specificity were calculated for the xTAG GPP for the seven principal diarrheal etiologies. The sensitivity and specificity for the xTAG GPP were >88% for Shigellaspp.,Campylobacterspp., rotavirus, norovirus genotype 1/2 (GI/GII), and adenovirus compared to those of microbiological culture and/or real-time PCR. However, the specificity was low (∼60%) for Salmonella species. Additionally, a number of important pathogens that are not identified in routine hospital procedures in this setting, such as Cryptosporidiumspp. and Clostridium difficile, were detected with the GPP. The use of the Luminex xTAG GPP for the detection of enteric pathogens in settings, like Vietnam, would dramatically improve the diagnostic accuracy and capacity of hospital laboratories, allowing for timely and appropriate therapy decisions and a wider understanding of the epidemiology of pathogens associated with severe diarrheal disease in low-resource settings

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Explicit Model Predictive Speed Control for Permanent Magnet Synchronous Motor With Torque Ripple Minimization

Permanent Magnet Synchronous Motors (PMSMs) are employed in various high-precision industrial applications. However, the torque ripple caused by nonideal factors, such as cogging torque, flux harmonics, and unbalanced stator phase currents diminishes motor performance. Therefore, torque ripple minimization is an important key in designing high-performance controllers for PMSMs. In this paper, an explicit model predictive speed control (EMPSC) is proposed as an advanced strategy for torque ripple minimization. First, the torque ripple is modeled as a periodic disturbance in the speed model. Subsequently, a Lyapunov-based periodic disturbance observer (PDOB) is designed to fast and accurately estimate the torque ripple. The EMPSC updates the estimated disturbance into the prediction model and minimizes the cost function to obtain the optimal control signal. This control signal effectively mitigates torque ripple while enhancing dynamic response performance. Furthermore, this paper introduces an explicit process aimed at significantly reducing the complexity and computational effort of the entire control scheme. Lastly, the simulation and experimental results are presented to demonstrate the effectiveness of the proposed method

Effect of the third-party warehouse on bullwhip effect and inventory cost in supply chains

In this research, we examine the impact of a third-party warehouse on the bullwhip effect in a three-stage supply chain with one supplier, one third-party warehouse and two retailers. We compare the bullwhip effect in this three-stage supply chain and that in a two-stage supply chain with only one supplier and two retailers. It is assumed that the demand process can be modeled with an AR(1) model and the base stock inventory policy is employed for both the third-party warehouse in the three-stage system and the two retailers in the two-stage system. It is found that the existence of the third-party warehouse has no influence on bullwhip effect when the lead times of the third-party warehouse and the two retailers are equal. For cases in which the third-party warehouse does not have any impact on bullwhip effect, we examine the impact of the third-party warehouse on the inventory cost in the supply chain by analyzing inventory cost savings obtained by the existence of the warehouse.Supply chain Bullwhip effect Autoregressive model Base stock policy Inventory cost

EFFECT OF REPLACING RICE BRAN OR FISH MEAL BY FRESH OR DRIED MULBERRY LEAVES ON DIGESTIBILITY AND NITROGEN RETENTION OF PIGS

Two experiments were conducted to study the effect of replacing rice bran or fishmeal by fresh or dried mulberry leaves on digestibility and nitrogen retention of pigs. Inexperiment 1, a double 4x4 Latin square design in a 2x4 factorial arrangement was used tostudy the effect of graded levels of mulberry leaf meal (0, 15, 30 and 50% on a dry basis,respectively) in diets based on rice brans and broken rice on the N balance of eight youngcastrate male Mong Cai pigs with a mean weight of 15 kg. Mulberry leaf meal (MLM)contained DM 30.4% and in the dry matter: ash 16.9, crude fibre 20.1 and crude protein(Nx6.25) 25.4%, respectively. Feed intake was calculated to be 50 g DM/kg body weight.Although not significant, DM and organic matter digestibility appeared to increase withincreasing levels of dietary MLM. Organic matter digestibility was significantly better(P&lt;0.05); N balance indices improved with the inclusion of MLM in the diet, and this effectwas significant for N retention (P&lt;0.05) when expressed as proportion of the digested N. Inexperiment 2, six Large White castrate male pigs, weighing on average 15 kg, wereallocated according to a balanced change-over design, to two diets where mulberry leaves,either in milled of sun-dried or chopped off fresh, contributed about 45% of the total dailyN intake in iso-nitrogenous diets (Nx6.25, 13.7% on a dry basis). There were no significanteffects of treatment on DM, organic matter and N digestibility but dry leaves wereassociated with slightly lower digestibility values. N balance tended to be better in pigs fedwith fresh mulberry leaves compared to mulberry leaf meal. It can be concluded that inrice-based diets, it is possible to use mulberry leaves as the main protein source.Keywords: Digestibility, leaves, mulberry, pigs, protein