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In this second part of the tutorial series, we continue the investigation of Petri net theory as it applies to laboratory automation systems. The focus of this tutorial is the application of theoretical results to the analysis of laboratory automation system models. The mathematical description of a Petri net is introduced. Several analytical methods are reviewed and applied to examples of laboratory automation systems. Analytical results include the identification of deadlock situations, computation of cycle times, optimization of design, and the automatic calculation of system-control schemes. [ABSTRACT FROM AUTHOR]

The Python programming language is reviewed, with an emphasis on features and add-on modules useful for solving problems in the field of laboratory automation. Complexities of multi-instrument automated system control and coordination are discussed, along with the difficulties that arise when multitasking is used to implement system controllers. We introduce Python's generators, a feature not found in other popular languages, and demonstrate how to use them to simplify the development of multi-instrument laboratory automation system controllers. [ABSTRACT FROM AUTHOR]

A move from fixed, statically scheduled laboratory automation systems to more dynamic and adaptive behavior introduces complexities and challenges that have not been thoroughly explored in the field of laboratory automation. Powerful tools are required for the systematic modeling, analysis, simulation, and control of such systems. In this first part of a tutorial series, we introduce and explore Petri nets as a tool that can be used to model dynamically controlled laboratory automation systems. Subsequent contributions to this series will look at formal mathematical techniques for analyzing Petri net models, and methods for simulating and controlling laboratory automation systems using Petri nets. [ABSTRACT FROM AUTHOR]

Tinea capitis is a dermatophytosis, which is more common in children. It is caused by dermatophytes that vary according to the region; the most frequently isolated dermatophyte in our setting is Microsporum canis. Given its anthropophilic nature, its dissemination via interpersonal transmission and through the use of hair care tools is very common. In the course of the past year, an increase has been reported in the incidence of a pathogen that was very rare in our setting: Trichophyton tonsurans. Here we describe a retrospective study of cases of tinea capitis caused by Trichophyton tonsurans identified between September 2021 and March 2023 in the Department of Pediatric Dermatology at a general hospital of the City of Buenos Aires., (Sociedad Argentina de Pediatría.)

The escalating global prevalence of bariatric procedures necessitates an enhanced focus on optimizing perioperative care for improved patient outcomes. This study focuses on the implementation of Enhanced Recovery After Bariatric Surgery (ERABS) protocols in Italian bariatric centers to optimize perioperative care. An online survey comprising 19 items was conducted in October 2023, targeting managing surgeons in 139 registered bariatric centers. This survey explored geographic and center-type variations, knowledge, and application of ERABS protocols, along with perioperative, intraoperative, and postoperative practices. Statistical analysis employed included one-way ANOVA and Tukey post hoc tests. Responses from 72 centers (51.8%) revealed a strong awareness of ERABS protocols among managing surgeons. Adherence rates varied geographically (46.3-63%) and among center types (60.8-56.3%). Perioperative practices, including the abandonment of antibiotics for perioperative prophylaxis by 77.5% of surgeons and the adoption of the TAP block technique in 69% of centers, aligned well with ERABS recommendations. However, inconsistencies were noted in abdominal drain usage (61.5% after SG; 70.5% after RYGB/OAGB), with a substantial percentage not adhering to ERABS guidelines. Intraoperative habits generally adhered to ERABS protocols, yet preferences for certain tests, particularly the methylene blue test (70.4%), deviated. Postoperative practices displayed positive trends, with early reintroduction of oral feeding (71.8%) and opioid-free pain management (71.8%). Variations existed in discharge timing and patient monitoring, indicating areas for further improvement. This study offers a comprehensive snapshot of ERABS protocol adherence in Italy, emphasizing the positive trend toward optimizing recovery and reducing patient stress. Despite variations, a majority of centers demonstrated commitment to ERABS principles. Ongoing education, interdisciplinary collaboration, and nationwide dialogue are essential for standardizing ERABS protocols and advancing bariatric-metabolic surgery outcomes in Italy., (© 2024. The Author(s).)

(1) Background: There is still disagreement over how sleeve gastrectomy (SG) affects gastroesophageal reflux disease (GERD). The debate regarding the best option for patients undergoing bariatric surgery who are also affected by GERD and/or hiatal hernia continues to divide the community of bariatric surgeons. While concomitant hiatal hernia repair (SG + HHR) has been proposed as a means of reducing the risk of GERD following SG with varying degrees of success, the addition of a fundoplication (SG + FP) has been suggested in recent years as a way to improve the lower esophageal sphincter's competency. The aim of this study is to systematically review and meta-analyze the efficacy of SG + HHR versus SG + FP on GERD remission in patients with obesity. (2) Methods: A systematic review of the literature was conducted, and studies analyzing the effects of SG + HHR versus SG + FP on postoperative GERD were included. The methodological quality of included trials was evaluated. The primary outcome was postoperative GERD rate, erosive esophagitis, and 12-month weight loss. Secondary outcomes included postoperative complications and mortality. The PRISMA guidelines were used to carry out the present systematic review (PROSPERO Registration Number: CRD42023405600). (3) Results: Fifteen articles with a total of 1164 patients were included in the meta-analysis; 554 patients underwent SG + HHR while 610 underwent SG + FP. In the SG + HHR group, 58.5 ± 28.9% of subjects presented clinical GERD symptoms compared to 20.4 ± 17.5% postoperatively ( p < 0.001). In the SG + FP group, 64.8 ± 39.4% were affected by GERD preoperatively compared to only 5 ± 8.1% postoperatively ( p < 0.001). SG + FP patients had a significantly greater GERD remission compared to SG + HHR ( p < 0.001). Weight loss was similar between groups ( p = 0.125). The rate of leaks was 0.18% and 0.33% in the SG + HHR and SG + FP, respectively ( p = 0.657), while perforations were significantly higher after SG + FP compared to the SG + HHR group (3.1% versus 0%, p = 0.002). The mortality rate was significantly greater in the SG + FP group (0.5% versus 0%, p = 0.002). (4) Conclusions: This study revealed that both SG with concomitant HHR and sleeve-fundoplication are effective in terms of reflux resolution and weight outcomes, with superiority of SG + FP in terms of GERD control, despite a greater overall complication rate. Both strategies can therefore be suggested as a suitable alternative variant to a conventional SG in subjects with obesity and concomitant hiatal hernia and/or GERD. Studies with extended follow-up and direct comparisons of these surgical approaches to conventional SG are warranted.

Background: Several methods have been proposed to monitor cerebral perfusion during carotid endarterectomy (CEA), with the purpose of minimizing the risk of perioperative stroke. The INVOS-4100 is able to detect cerebral oxygen saturation providing an intraoperative real-time monitoring system of cerebral oximetry. The aim of this study was to evaluate the performance of the INVOS-4100 in predicting cerebral ischemia during CEA., Methods: Between January 2020 and May 2022, 68 consecutive patients were scheduled for CEA either under general anesthesia or regional anesthesia with deep and superficial cervical block. Vascular oxygen saturation was recorded continually through INVOS before and during clamping of the ICA. Awake testing was performed in the group of patients undergoing CEA under regional anesthesia., Results: Sixty-eight patients were included; 43 were males (63.2%). Severe stenosis of the artery was present in 92%. Forty-one (60.3%) patients were monitored by INVOS, while 22 (39.7%) underwent awake testing. Mean clamping time was 20 ± 6.6 min. Patients undergoing awake testing had a lower hospital stay and ICU stay during admission ( p  = 0.011 and p  = 0.007 respectively). Comorbidities correlated with a higher ICU stay ( p  < 0.05). The INVOS monitoring was able to predict ischemic events with a sensitivity of 98% (AUC = 0.976)., Conclusions: The present study demonstrates that cerebral oximetry monitoring was a strong predictor of cerebral ischemia, although it was not possible to determine the non-inferiority of cerebral oximetry compared to awake testing. Nonetheless, the use of cerebral oximetry evaluates only perfusion in the superficial brain tissue and an absolute rSO2 value corresponding to significant cerebral ischemia has not been established. Therefore, larger prospective studies that correlate cerebral oximetry with neurologic outcomes are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Russo, Gentile, Fenga, Izzo, Denaro, Luka, Frattaroli, Costanzo, Castagneto-Gissey and Salvati.)

Introduction : Despite several perioperative care advancements and innovations in surgical procedures and technologies, the incidence rate of anastomotic leaks (ALs) after colorectal surgery has not substantially decreased. Gut microbiota can play a critical role in the healing process of anastomotic tissue and alterations in its composition may be largely to blame for anastomotic insufficiency. The use of specific antibiotics for preoperative large bowel decontamination could significantly influence the rate of ALs. The aim of this study was to systematically assess the various antibiotic prophylactic regimen strategies for primary prevention of ALs during colorectal surgery, in view of the available evidence. Methods : A systematic review of the literature was conducted, and randomized clinical trials (RCTs) analyzing prophylactic antibiotic bowel preparation in colorectal surgery were included. PubMed, Embase, the Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched from inception through to 30 November 2022. The methodological quality of the included trials was evaluated. The primary outcome was AL rate; secondary outcomes were superficial/deep surgical site infections (SSIs). The PRISMA guidelines were used to carry out the present systematic review. Results: Thirteen RCTs published between 1977 and 2022, with a total of 4334 patients were included in the meta-analysis. Antibiotic prophylaxis was administered orally in 11/13 studies and intravenously in 2 studies. Patients randomly assigned to antibiotic prophylaxis, regardless of the regimen, had a reduced risk of ALs ( p = 0.003) compared to mechanical bowel preparation (MBP) alone. The use of antibiotic prophylaxis was also more effective in significantly reducing SSIs ( p < 0.001). Conclusions: The evidence points to an advantage of oral antibiotic prophylaxis in terms of AL rate, a significant contributor to perioperative morbidity, mortality, and rising healthcare expenditures. In light of such results, the use of antibiotic prophylaxis should be strongly encouraged prior to colorectal surgery.

Aim: To investigate the prevalence of biopsy-proven non-alcoholic steatohepatitis (NASH) in a cohort of patients with morbid obesity and with or without type 2 diabetes (T2D) and to find non-invasive predictors of NASH severity., Methods: We evaluated a cohort of 412 subjects (age 19-67 years, body mass index-BMI: 44.98 kg/m 2 ), who underwent fine-needle liver biopsy during bariatric surgery. Thirty-six percent of the subjects were affected by T2D. Liver biopsies were classified according to the Kleiner's NAFLD Activity Score (NAS). NAFLD Fibrosis Score (NFS), AST/ALT ratio, AST to Platelet ratio (APRI), fibrosis-4 score (FIB4) were calculated. A neural network analysis (NNA) was run to predict NASH severity., Results: The prevalence of biopsy-proven NASH was 63% and 78% in subjects with obesity and without or with T2D, respectively. T2D doubled the risk of NASH [OR 2.079 (95% IC=1.31-3.29)]. The prevalence of NAFL increased with the increase of BMI, while there was an inverse correlation between BMI and NASH (r=-0.145 p=0.003). Only mild liver fibrosis was observed. HOMA-IR was positively associated with hepatocyte ballooning (r=0.208, p<0.0001) and fibrosis (r=0.159, p=0.008). The NNA highlighted a specificity of 77.3% using HDL-cholesterol, BMI, and HOMA-IR as main determinants of NASH., Conclusions: Our data show a higher prevalence of NASH in patients with morbid obesity than reported in the literature and the pivotal role of T2D among the risk factors for NASH development. However, the inverse correlation observed between BMI and biopsy-proven NASH suggests that over a certain threshold adiposity can be somewhat protective against liver damage. Our model predicts NASH presence with high specificity, thus helping identifying subjects who should promptly undergo liver biopsy., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

(1) Background: Fluorescence cholangiography has been proposed as a method for improving the visualization and identification of extrahepatic biliary anatomy in order to possibly reduce injuries and related complications. The most common method of indocyanine green (ICG) administration is the intravenous route, whereas evidence on direct ICG injection into the gallbladder is still quite limited. We aimed to compare the two different methods of ICG administration in terms of the visualization of extrahepatic biliary anatomy during laparoscopic cholecystectomy (LC), analyzing differences in the time of visualization, as well as the efficacy, advantages, and disadvantages of both modalities. (2) Methods: A total of 35 consecutive adult patients affected by acute or chronic gallbladder disease were enrolled in this prospective case−control study. Seventeen patients underwent LC with direct gallbladder ICG injection (IC-ICG) and eighteen subjects received intravenous ICG administration (IV-ICG). (3) Results: The groups were comparable with regard to their demographic and perioperative characteristics. The IV-ICG group had a significantly shorter overall operative time compared to the IC-ICG group (p = 0.017). IV-ICG was better at delineating the duodenum and the common hepatic duct compared to the IC-ICG method (p = 0.009 and p = 0.041, respectively). The cystic duct could be delineated pre-dissection in 76.5% and 66.7% of cases in the IC-ICG and IV-ICG group, respectively, and this increased to 88.2% and 83.3% after dissection. The common bile duct could be highlighted in 76.5% and 77.8% of cases in the IC-ICG and IV-ICG group, respectively. Liver fluorescence was present in one case in the IC-ICG group and in all cases after IV-ICG administration (5.8% versus 100%; p < 0.0001). (4) Conclusions: The present study demonstrates how ICG-fluorescence cholangiography can be helpful in identifying the extrahepatic biliary anatomy during dissection of Calot’s triangle in both administration methods. In comparison with intravenous ICG injection, the intracholecystic ICG route could provide a better signal-to-background ratio by avoiding hepatic fluorescence, thus increasing the bile duct-to-liver contrast.

Background: Hyperglycemia and obesity are associated with a worse prognosis in subjects with COVID-19 independently. Their interaction as well as the potential modulating effects of additional confounding factors is poorly known. Therefore, we aimed to identify and evaluate confounding factors affecting the prognostic value of obesity and hyperglycemia in relation to mortality and admission to the intensive care unit (ICU) due to COVID-19., Methods: Consecutive patients admitted in two Hospitals from Italy (Bologna and Rome) and three from Spain (Barcelona and Girona) as well as subjects from Primary Health Care centers. Mortality from COVID-19 and risk for ICU admission were evaluated using logistic regression analyses and machine learning (ML) algorithms., Results: As expected, among 3,065 consecutive patients, both obesity and hyperglycemia were independent predictors of ICU admission. A ML variable selection strategy confirmed these results and identified hyperglycemia, blood hemoglobin and serum bilirubin associated with increased mortality risk. In subjects with blood hemoglobin levels above the median, hyperglycemic and morbidly obese subjects had increased mortality risk than normoglycemic individuals or non-obese subjects. However, no differences were observed among individuals with hemoglobin levels below the median. This was particularly evident in men: those with severe hyperglycemia and hemoglobin concentrations above the median had 30 times increased mortality risk compared with men without hyperglycemia. Importantly, the protective effect of female sex was lost in subjects with increased hemoglobin levels., Conclusions: Blood hemoglobin substantially modulates the influence of hyperglycemia on increased mortality risk in patients with COVID-19. Monitoring hemoglobin concentrations seem of utmost importance in the clinical settings to help clinicians in the identification of patients at increased death risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mayneris-Perxachs, Russo, Ramos, de Hollanda, Arxé, Rottoli, Arnoriaga-Rodríguez, Comas-Cufí, Bartoletti, Verrastro, Gudiol, Fages, Giménez, Gil, Bernante, Tinahones, Carratalà, Pagotto, Hernández-Aguado, Fernández-Aranda, Meira, Castro Guardiola, Mingrone and Fernández-Real.)

Aims: Adults affected by obesity are at higher risk of premature mortality. Medications can help to lose weight and to maintain weight loss. Aim of this meta-analysis was to assess whether anti-obesity medications affect all-cause mortality, mortality due to cardiovascular events, cardiovascular risk factors and body weight., Data Synthesis: A Medline search was performed to identify randomized controlled trials (RCTs) of anti-obesity medications in adults with overweight or obesity reporting data on all-cause mortality, cardiovascular mortality or non-fatal cardiovascular events, with a follow-up of at least 6 months. We identified 28 RCTs with 50,106 participants. The median follow-up was 52 weeks. Evidence did not show superiority of anti-obesity medications over placebo in reducing all-cause mortality (risk ratio 1.03, 95%Confidence Interval [CI] 0.87 to 1.21) or cardiovascular mortality (risk ratio 0.92, 95%CI 0.72 to 1.18). All-cause mortality rate was positively associated with weight loss (β = 0.0007; p = 0.045); hence, for each kg of body weight lost there was a 0.07% decrease of all-cause mortality. The pharmacological treatment reduced total-cholesterol (7.15 mg/dl; 95%CI 1.46-12.85), LDL-cholesterol (5.06 mg/dl; 95%CI 1.12-9.00), and triglycerides levels (9.88 mg/dl; 95%CI 5.02-14.75), while it increased HDL-cholesterol (1.37 mg/dl; 95%CI 0.17-2.57). Systolic blood pressure decreased (0.90 mmHg; 95%CI 0.15-1.64)., Conclusions: Although we were unable to demonstrate a superiority of anti-obesity medications over placebo on mortality, metaregression showed that even a small weight reduction tends to reduce all-cause mortality in obesity. Our data support public health measures to reduce the obesity burden by including the use of anti-obesity medications., Registration Number (prospero): CRD42020210329., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Context: Nonalcoholic steatohepatitis (NASH) is considered the hepatic counterpart of metabolic syndrome., Objective: This work aimed to investigate the determinants of NASH reversal in patients undergoing biliopancreatic diversion (BPD) in a 5-year follow-up study., Methods: This prospective study was conducted at Policlinico Universitario Agostino Gemelli. A total of 37 patients underwent fine-needle liver biopsy during BPD. Ultrasonography-guided percutaneous liver biopsy was obtained 5 years after the operation. The primary outcome of our study was histologic NASH reversal at 5-year follow-up. To better characterize the clinical variables involved in the resolution of NASH, we also compared patients without histologic NASH resolution at 5 years with those in whom NASH had disappeared., Results: At follow-up, NASH had reversed in 56.5% of the patients. The NAFLD activity score (NAS) improved from 3.7 ± 0.93 to 2 ± 1.11 (P < .001). Fibrosis reversed in 16% patients (P = .022), and 32% improved (95% CI, 0.05-0.54). No significant differences in body mass index or clinical parameters changes explained the effect of surgery on NASH, apart from the measure of insulin sensitivity post surgery. The Homeostasis Model Assessment of Insulin Resistance decreased from 3.31 ± 1.72 at baseline to 1.73 ± 1.08 (P < .001) after BPD, and the Matsuda index improved from 2.66 ± 1.79 to 4.73 ± 3.05 (P < .001). The lipid profile normalized (total cholesterol from 4.75 ± 1.18 to 3.32 ± 0.77 mmol/L, P < .001; low-density lipoprotein cholesterol from 2.92 ± 0.91 to 1.60 ± 0.51 mmol/L, P = .0001; high-density lipoprotein cholesterol from 0.97 ± 0.33 to 1.10 ± 0.35 mmol/L, P = .023; triglycerides from 2.52 ± 1.6 to 1.47 ± 0.67 mmol/L, P = .003). Neural network analysis showed that the end-study Matsuda index discriminated between responders and nonresponders with high accuracy (receiver operating characteristic area under the curve = 0.98%)., Conclusion: Remission of NASH is driven by reversal of whole-body insulin resistance post intervention., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver-related mortality. NAFLD is associated with obesity, hepatic fat accumulation, and insulin resistance, all of which contribute to its pathophysiology. Weight-loss is the main therapy for NAFLD, and metabolic surgery is the most effective treatment for morbid obesity and its metabolic comorbidities. Although has been reported that Roux-en-Y gastric bypass can reverse NAFLD, it is unclear whether such effects result from reduced weight, from a lower calorie-intake, or from the direct influence of surgery on mechanisms contributing to NAFLD. We aimed to investigate whether gastrointestinal (GI) bypass surgery could induce direct effects on hepatic fat accumulation and insulin resistance, independently of weight reduction. Twenty Wistar rats on a high-fat diet underwent duodenal-jejunal-bypass (DJB) or sham operation and were pair fed (PF) for 15 wk after surgery to obtain a matched weight. Outcome measures include ectopic fat deposition, expression of genes and proteins involved in fat metabolism, insulin-signaling, and gluconeogenesis in liver and muscle. Despite no differences in body weight and calorie intake, DJB showed lower ectopic fat accumulation, improved peripheral and hepatic insulin sensitivity, and enhanced lipid droplet degradation. In both tissues, DJB increased insulin signaling, whereas hepatic key enzymes involved in gluconeogenesis and de novo lipogenesis were decreased. These findings suggest that DJB can reverse, independently of weight loss, ectopic fat deposition and insulin resistance, two features of NAFLD that share a mutual pathway, in which perilipin-2 (PLIN2) seems to be the main player, supporting further investigation into strategies that target the gut to treat metabolic liver diseases. NEW & NOTEWORTHY Our findings suggest that duodenal-jejunal bypass can reverse, independently of weight loss, ectopic fat deposition and insulin resistance, two features of nonalcoholic fatty liver disease that share a mutual pathway, in which perilipin-2 seems to be the main player. Our study supports further investigation into the role of proximal small intestine exclusion in the pathophysiology of nonalcoholic fatty liver disease to uncover less invasive treatments that mimic the effects of metabolic surgery and aims to prevent and treat metabolic liver disease.

We describe a custom Internet of Things (IoT) device used for tracking barcoded containers end to end in a high-throughput analysis and purification laboratory. Our IoT device fills an important gap that previously prevented us from fully tracking barcoded sample containers through manual steps in a multistep workflow, such as when samples are "parked" for temporary storage, or when using instrumentation not otherwise equipped with barcode scanners, a common occurrence found with specific centrifugal evaporation instruments. The custom device reads container barcodes and sends a small amount of data to our back-end data systems. Once data have been received and processed, users are alerted to any system responses via aural and visual feedback. Components of the IoT system include a low-cost headless IoT computer, a barcode reader, and a multicolor LED strip. We believe that the model for our device will facilitate simple and rapid deployment of IoT to the broader laboratory community. All source code and device configurations will be released into the public domain and made freely available.

Objectives: The main purpose of this study was to estimate the incidence rate and prevalence of clinically relevant pituitary adenomas (PAs) within the Hospital Italiano Medical Care Program (HIMCP), a well-defined population of 150,000 members living in the urban and suburban area of the city of Buenos Aires. We defined clinically relevant PAs as those associated with endocrine dysfunction and/or mass effect., Subjects and Methods: A retrospective open cohort study was conducted, including all members of the HIMCP over 18 years old, with active memberships during the period of the study, from January 1st 2003, to January 1, 2014. The incidence rates (IRs) were standardized (SIR) to the World Health Organization (WHO) 2000 standard population and were expressed per 100,000 members/year. Prevalence was estimated at January 1, 2014, and was expressed per 100,000 persons. The clinical records have been electronically managed since 2001. All lab and imaging studies were done in-house., Results: The overall SIR was 7.39/100,000/year (95% CI 4.47-10.31). Female patients had a specific IR significantly higher than male patients (5.85 vs.1.54) and represented 73% of the affected members. Regarding tumor size, 61.4% were microadenomas, and the mean age at diagnosis was 46.4 years. Prolactinomas had the highest SIR (5.41), followed by acromegaly (Acro) and non-functioning adenomas (NFAs) with overlapping 95% CIs (0.44-1.41 and 0.31-0.99, respectively). Microprolactinomas were more frequent in female (72.6%) (p < 0.01) and younger members (38 vs.60 years; p < 0.04). The overall prevalence rate was 97.76/100,000. Prolactinomas had the highest prevalence (56.29), followed by NFAs (21.48), Acro (14.07) and CD (5.93)., Conclusion: Our results demonstrate that clinically relevant PAs are more common than usually suspected, especially prolactinomas and growth-hormone secreting PAs. These data highlight the need to increase the awareness of PAs, thereby enabling early diagnosis and treatment.

A scheduler has been developed for an integrated laboratory robot system that operates in an always-on mode. The integrated system is designed for imaging plates containing protein crystallization experiments, and it allows crystallographers to enter plates at any time and request that they be imaged at multiple time points in the future. The scheduler must rearrange tasks within the time it takes to image one plate, trading off the quality of the schedule for the speed of the computation. For this reason, the scheduler was based on a simulated annealing algorithm with an objective function that makes use of a linear programming solver. To optimize the scheduler, extensive computational simulations were performed involving a difficult but representative scheduling problem. The simulations explore multiple configurations of the simulated annealing algorithm, including both geometric and adaptive annealing schedules, 3 neighborhood functions, and 20 neighborhood diameters. An optimal configuration was found that produced the best results in less than 60 seconds, well within the window necessary to dynamically reschedule imaging tasks as new plates are entered into the system., (© 2014 Society for Laboratory Automation and Screening.)

A systematic method for assembling and solving complex compound distribution problems is presented in detail. The method is based on a model problem that enumerates the mathematical equations and constraints describing a source container, liquid handler, and three types of destination containers involved in a set of compound distributions. One source container and one liquid handler are permitted in any given problem formulation, although any number of compound distributions may be specified. The relative importance of all distributions is expressed by assigning weights, which are factored into the final mathematical problem specification. A computer program was created that automatically assembles and solves a complete compound distribution problem given the parameters that describe the source container, liquid handler, and any number and type of compound distributions. Business rules are accommodated by adjusting weighting factors assigned to each distribution. An example problem, presented and explored in detail, demonstrates complex and nonintuitive solution behavior.

In this study we have examined the combustion dynamics of 1,5-dinitrobiuret (DNB) and nitric acid using reactive molecular dynamics simulations. Simulations were performed using the ReaxFF force field with parameters that were fitted against quantum mechanical calculations on model compounds/clusters relevant for this particular chemical system. Several different compositions were investigated, at densities of 0.5 and 1.0 g/mL, to examine the reaction kinetics in a dense vapor and liquid phase of these mixtures. Our simulations show that at certain compositions of the mixture reaction kinetics result in a very sharp release of thermal energy, which we associate with spontaneous ignition or hypergolicity. Analysis of key reaction mechanisms responsible for this process is discussed.

Computational chemistry simulations were performed to determine the effect that the addition of a single formic acid molecule has on the structure and stability of protonated water clusters. Previous experimental studies showed that addition of formic acid to protonated pure water results in higher intensities of large-sized clusters when compared to pure water and methanol-water mixed clusters. For larger, protonated clusters, molecular dynamics simulations were performed on H(+)(H(2)O)(n), H(+)(H(2)O)(n)CH(3)OH, and H(+)(H(2)O)(n)CHOOH clusters, 19-28 molecules in size, using a reactive force field (ReaxFF). Based on these computations, formic acid-water clusters were found to have significantly higher binding energies per molecule. Addition of formic acid to a water cluster was found to alter the structure of the hydrogen-bonding network, creating selective sites within the cluster, enabling the formation of new hydrogen bonds, and increasing both the stability of the cluster and its rate of growth.

The total sputtering yields for water ice due to kiloelectronvolt cluster bombardment have been measured and compared to the predictions made by the mesoscale energy deposition footprint (MEDF) model. For C60 bombardment, the experimental yield varies almost linearly from 820 water molecule equivalents at an incident kinetic energy of 10 keV to 10 100 water molecule equivalents at a kinetic energy of 120 keV. For Au3 bombardment, the experimental yield varies almost linearly from 630 water molecule equivalents at an incident energy of 10 keV and rises to 1200 water molecule equivalents at 25 keV. The MEDF model is used to calculate relative yield trends with respect to incident energy using short-time molecular dynamics simulations. The results of these calculations indicate that the model can effectively predict the yield trends observed for these two clusters in experiments, although there is a consistent overestimate of the predicted induced C60 yield. It is hypothesized that this overestimate can be explained by the absence of reactions and ionization processes in the current simulations. Despite this omission, experimental yield trends can be accurately predicted using relatively small amounts of computer time. The success of the model in predicting the yield of water from ice films using a variety of energies and projectiles suggests this approach may greatly aid in the optimization of experimental configurations.

Molecular dynamics simulations have been performed to model 5-keV C60 and Au3 projectile bombardment of an amorphous water substrate. The goal is to obtain detailed insights into the dynamics of motion in order to develop a straightforward and less computationally demanding model of the process of ejection. The molecular dynamics results provide the basis for the mesoscale energy deposition footprint model. This model provides a method for predicting relative yields based on information from less than 1 ps of simulation time.

The ion beam-induced removal of thin water ice films condensed onto Ag and bombarded by energetic Au, Au2, Au3, and C60 projectiles is examined both experimentally and with molecular dynamics computer simulations. For water overlayers of thicknesses greater than 10 A, the yields of sputtered Ag+ secondary ions decay exponentially with increasing ice thickness, revealing characteristic decay lengths of 24, 20, 18, and 7.0 A, respectively. It is shown that these values manifest the characteristic depths of projectile energy loss, rather than escape depths of the sputtered Ag atoms through the water ice overlayer. Computer simulations show that the mechanism of ejection involves the sweeping away of overlayer water molecules, allowing for an unimpeded escape of ejected Ag atoms. The relevance of these data with respect to surface sensitivity in secondary ion mass spectrometry is discussed.

The DeWitt formula for inertia ellipsoids mapped by stereographic projection coordinates is developed. We discover that by remapping the quaternion parameter space with stereographic projections, considerable simplification of the differential geometry for the inertia ellipsoid with spherical symmetry takes place. The metric tensor is diagonal and contains only one independent element in that case. We find no difficulties testing and implementing the DeWitt formula for the inertia ellipsoids of asymmetric tops mapped by stereographic projections. The path integral algorithm for the treatment of Rm x S2 manifolds based on a mixture of Cartesian and stereographic projection coordinates is tested for small Arn-HF clusters in the n = 2 to n = 5 range. In particular, we determine the quantum effects of the red shift and the isomerization patterns at finite temperatures. Our findings are consistent with previously reported computations and experimental data for small Arn-HF clusters., (Copyright 2004 American Institute of Physics)

Purpose: To assess the comparative therapeutic value of valproate (VPA), lamotrigine (LTG), and their combination in patients with complex partial seizures resistant to other established antiepileptic drugs (AEDs)., Methods: After a 3-month prospective baseline, 20 adults with refractory complex partial seizures not exposed previously to VPA and LTG were scheduled to receive three consecutive add-on treatments with VPA, LTG, or their combination, according to an open, response-conditional, crossover design. Each period consisted of a 6- to 12-week dose optimization followed by 3-month evaluation at stabilized serum drug levels. Only patients not responding to one phase proceeded to the next., Results: A >50% reduction in seizure frequency was observed in three of 20 patients given VPA and in four of 17 patients given LTG. Of the remaining 13 patients, four became seizure free, and an additional four experienced seizure reductions of 62-78% when VPA and LTG were given in combination. Mild tremor was observed in three patients receiving VPA and in all patients taking the VPA--LTG combination. In patients responding to combination therapy, optimized dosages and peak serum levels of both VPA and LTG were lower than those during separate administration., Conclusions: A considerable proportion of patients who failed to respond to VPA and LTG separately improved when the two drugs were combined, although serum levels of both agents were lower during combination therapy. Despite methodologic limitations in the nonrandomized treatment sequence, these findings suggest that VPA and LTG exhibit a favorable pharmacodynamic interaction in patients with refractory partial epilepsy. The dosage of both drugs, however, may need to be reduced to minimize the risk of intolerable side effects.

A prospective study of conduct disorder (CD) was conducted using 4 annual structured diagnostic interviews of 171 clinic-referred boys, their parents, and their teachers. Only about half of the 65 boys who met criteria for CD in Year 1 met criteria again during the next year, but 88% met criteria for CD again at least once during the next 3 years. For most boys with CD, the number of symptoms fluctuated above and below the diagnostic threshold from year to year but remained relatively high. Lower socioeconomic status, parental antisocial personality disorder (APD), and attention-deficit hyperactivity disorder were significant correlates of CD in Year 1, but the interaction of parental APD and the boy's verbal intelligence predicted the persistence of CD symptoms over time (i.e., only boys without a parent with APD and with above-average verbal intelligence clearly improved).

Jeffrey A. Gray has proposed a model in which conduct disorder (CD) is viewed as the result of both excessive activity of a behavioral activation system that mediates appetitive and aggressive behavior and deficient activity of a behavioral inhibition system that mediates both anxiety and the inhibition of behavior in the presence of cues signalling impending punishment or frustration. The relation of anxiety to antisocial behavior was examined in 177 clinic-referred boys, aged 7 to 12 years, 68 of whom met DSM-III-R criteria for CD. As predicted by Gray's model, boys with CD and comorbid anxiety disorder were markedly less impaired than boys with CD alone.

Early motherhood (less than 20 years of age) was found to be significantly correlated (r = .33) with the number of DSM-III symptoms of conduct disorder in a sample of 253 boys aged 6-13 years who had been referred to outpatient clinics. The following models were compared using path analysis: (a) Teenage motherhood, parental antisocial personality, and SES each contribute uniquely to the prediction of childhood conduct problems; (b) teenage motherhood mediates the association of SES and parental antisocial personality with child conduct problems; and (c) teenage motherhood is spuriously related with child conduct problems because of common associations with SES and parental antisocial personality. Model (c) best fit our data. Similar results were obtained whether maternal age at the birth of the firstborn child or the proband child was used to define maternal age and when teenage motherhood was defined as giving birth at less than 18 years.

A structured and reliable diagnostic procedure based on a revised version of the Diagnostic Interview Schedule for Children for children, parents, and teachers was used to assign both DSM-III and DSM-III-R diagnoses to 177 outpatient boys aged 7 to 12 years. Compared to their DSM-III counterparts, DSM-III-R oppositional defiant disorder was 25.5% less prevalent, DSM-III-R dysthymia was 37.8% less prevalent, and DSM-III-R conduct disorder (CD) was 44.3% less prevalent. However, DSM-III-R attention deficit hyperactivity disorder was 14.4% more prevalent than DSM-III attention deficit disorder with hyperactivity. The two definitions of CD were compared to exemplify an empirical approach to diagnostic validation. The DSM-III-R diagnosis of CD appears to be more valid as it is more strongly associated with police contacts, school suspensions, and history of antisocial personality disorder in the biological father, but both CD diagnoses are associated with family histories of criminal convictions.

The biological mothers of 100 outpatient children aged 6-13 years completed the Minnesota Multiphasic Personality Inventory (MMPI). Mothers of children given DSM-III diagnoses of conduct disorder (CD; n = 13) had significantly higher scores on MMPI scales associated with antisocial behavior (Pd and Ma), histrionic behavior (Hs and Hy), and disturbed adjustment (Sc). In contrast, the children's diagnosis of attention deficit disorder with hyperactivity (ADD/H; n = 22) was not significantly associated with any maternal MMPI elevations, and the CD x ADD/H interactions were not significant for any MMPI scale. These results indicate that CD is linked to maternal personality disorder, but ADD/H is not.