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Background: The Omnipod® 5 Automated Insulin Delivery (AID) System was shown to be safe and effective following 3 months of use in people with type 1 diabetes (T1D); however, data on the durability of these results are limited. This study evaluated the long-term safety and effectiveness of Omnipod 5 use in people with T1D during up to 2 years of use. Materials and Methods: After a 3-month single-arm, multicenter, pivotal trial in children (6–13.9 years) and adolescents/adults (14–70 years), participants could continue system use in an extension phase. HbA1c was measured every 3 months for up to 15 months; continuous glucose monitor metrics were collected for up to 2 years. Results: Participants (N = 224) completed median (interquartile range) 22.3 (21.7, 22.7) months of AID. HbA1c was reduced in the pivotal trial from 7.7% ± 0.9% in children and 7.2% ± 0.9% in adolescents/adults to 7.0% ± 0.6% and 6.8% ± 0.7%, respectively, (P < 0.0001), and was maintained at 7.2% ± 0.7% and 6.9% ± 0.6% after 15 months (P < 0.0001 from baseline). Time in target range (70–180 mg/dL) increased from 52.4% ± 15.6% in children and 63.6% ± 16.5% in adolescents/adults at baseline to 67.9% ± 8.0% and 73.8% ± 10.8%, respectively, during the pivotal trial (P < 0.0001) and was maintained at 65.9% ± 8.9% and 72.9% ± 11.3% during the extension (P < 0.0001 from baseline). One episode of diabetic ketoacidosis and seven episodes of severe hypoglycemia occurred during the extension. Children and adolescents/adults spent median 96.1% and 96.3% of time in Automated Mode, respectively. Conclusion: Our study supports that long-term use of the Omnipod 5 AID System can safely maintain improvements in glycemic outcomes for up to 2 years of use in people with T1D. Clinical Trials Registration Number: NCT04196140 [ABSTRACT FROM AUTHOR]

BACKGROUND: Schools are important arenas for the promotion of critical health literacy (CHL) among adolescents. Key domains of CHL are information appraisal, understanding social determinants of health, and abilities to act on determinants of health. In this paper, we examine the psychometric properties of the Critical Health Literacy for Adolescents Questionnaire (CHLA‐Q). METHODS: A cross‐sectional survey study was performed at 5 schools in Norway. Respondents included 522 pupils aged 13‐15 years old. Confirmatory factor analysis (CFA) was conducted to examine the structural validity. Internal reliability was assessed using ordinal Cronbach's alpha. RESULTS: The estimated model had acceptable closeness of fit. Five of 6 scales displayed adequate internal reliability. CONCLUSION: The results indicate acceptable fit of the CHLA‐Q framework and that 5 of the 6 scales are applicable to inform future research and interventions. More research is needed on measurement of the second domain of CHL. [ABSTRACT FROM AUTHOR]

The moose Alces alces is the largest herbivore in the boreal forest biome, where it can have dramatic impacts on ecosystem structure and dynamics. Despite the importance of the boreal forest biome in global carbon cycling, the impacts of moose have only been studied in disparate regional exclosure experiments, leading to calls for common analyses across a biome‐wide network of moose exclosures.In this study, we use airborne laser scanning (ALS) to analyse forest canopy responses to moose across 100 paired exclosure‐control experimental plots distributed across the boreal biome, including sites in the United States (Isle Royale), Canada (Quebec, Newfoundland), Norway, Sweden and Finland.We test the hypotheses that canopy height, vertical complexity and above‐ground biomass (AGB) are all reduced by moose and that the impacts vary with moose density, productivity, temperature and pulse disturbances such as logging and insect outbreaks.We find a surprising convergence in forest canopy response to moose. Moose had negative impacts on canopy height, complexity and AGB as expected. The responses of canopy complexity and AGB were consistent across regions and did not vary along environmental gradients. The difference in canopy height between exclosures and open plots was on average 6 cm per year since the start of exclosure treatment (±2.1 SD). This rate increased with temperature, but only when moose density was high.The difference in AGB between moose exclosures and open plots was 0.306 Mg ha−1 year−1 (±0.079). In browsed plots, stand AGB was 32% of that in the exclosures, a difference of 2.09 Mg ha−1. The uniform response allows scaling of the estimate to a biome‐wide impact of moose of the loss of 448 (±115) Tg per year, or 224 Tg of carbon.Synthesis: Analysis of ALS data from distributed exclosure experiments identified a largely uniform response of forest canopies to moose across regions, facilitating scaling of moose impacts across the whole biome. This is an important step towards incorporating the effect of the largest boreal herbivore on the carbon cycling of one of the world's largest terrestrial biomes. [ABSTRACT FROM AUTHOR]

Background: The Tandem Control-IQ (CIQ) system has demonstrated significant glycemic improvements in large randomized controlled and real-world trials. Use of this system is lower in people with type 1 diabetes (T1D) government-sponsored insurance and those with type 2 diabetes (T2D). This analysis aimed to evaluate the performance of CIQ in these groups. Methods and Materials: A retrospective analysis of CIQ users was performed. Users age ≥6 years with a t:slim X2 Pump and >30 days of continuous glucose monitoring (CGM) data pre-CIQ and >30 days post-CIQ technology initiation were included. Results: A total of 4243 Medicare and 1332 Medicaid CIQ users were analyzed among whom 5075 had T1D and 500 had T2D. After starting CIQ, the Medicare beneficiaries group saw significant improvement in time in target range 70-180 mg/dL (TIR; 64% vs. 74%; P < 0.0001), glucose management index (GMI; 7.3% vs. 7.0%; P < 0.0001), and the percentage of users meeting American Diabetes Association (ADA) CGM Glucometrics Guidelines (12.8% vs. 26.3%; P < 0.0001). The Medicaid group also saw significant improvement in TIR (46% vs. 60%; P < 0.0001), GMI (7.9% vs. 7.5%; P < 0.0001), and percentage meeting ADA guidelines (5.7% vs. 13.4%; P < 0.0001). Patients with T2D and either insurance saw significant glycemic improvements. Conclusions: The CIQ system was effective in the Medicare and Medicaid groups in improving glycemic control. The T2D subgroup also demonstrated improved glycemic control with CIQ use. Glucometrics achieved in this analysis are comparable with those seen in previous randomized controlled clinical trials with the CIQ system. [ABSTRACT FROM AUTHOR]

Introduction: This trial assessed safety and effectiveness of an advanced hybrid closed-loop (AHCL) system with automated basal (Auto Basal) and automated bolus correction (Auto Correction) in adolescents and adults with type 1 diabetes (T1D). Materials and Methods: This multicenter single-arm study involved an intent-to-treat population of 157 individuals (39 adolescents aged 14-21 years and 118 adults aged ≥22-75 years) with T1D. Study participants used the MiniMed™ AHCL system during a baseline run-in period in which sensor-augmented pump +/- predictive low glucose management or Auto Basal was enabled for ∼14 days. Thereafter, Auto Basal and Auto Correction were enabled for a study phase (∼90 days), with glucose target set to 100 or 120 mg/dL for ∼45 days, followed by the other target for ∼45 days. Study endpoints included safety events and change in mean A1C, time in range (TIR, 70-180 mg/dL) and time below range (TBR, <70 mg/dL). Run-in and study phase values were compared using Wilcoxon signed-rank test or paired t-test. Results: Overall group time spent in closed loop averaged 94.9% ± 5.4% and involved only 1.2 ± 0.8 exits per week. Compared with run-in, AHCL reduced A1C from 7.5% ± 0.8% to 7.0% ± 0.5% (<0.001, Wilcoxon signed-rank test, n = 155), TIR increased from 68.8% ± 10.5% to 74.5% ± 6.9% (<0.001, Wilcoxon signed-rank test), and TBR reduced from 3.3% ± 2.9% to 2.3% ± 1.7% (<0.001, Wilcoxon signed-rank test). Similar benefits to glycemia were observed for each age group and were more pronounced for the nighttime (12 AM-6 AM). The 100 mg/dL target increased TIR to 75.4% (n = 155), which was further optimized at a lower active insulin time (AIT) setting (i.e., 2 h), without increasing TBR. There were no severe hypoglycemic or diabetic ketoacidosis events during the study phase. Conclusions: These findings show that the MiniMed AHCL system is safe and allows for achievement of recommended glycemic targets in adolescents and adults with T1D. Adjustments in target and AIT settings may further optimize glycemia and improve user experience. Clinical Trial Registration number: NCT03959423. [ABSTRACT FROM AUTHOR]

• No baseline Glx and tNAA abnormalities observed in OCD vs HC. • Although strong therapeutic response of ERP, no effects on metabolites in OCD patients. • Metabolite abnormalities in OCD seem to be dependent on mood disorder comorbidity. The dorsal anterior cingulate cortex (dACC) plays an important role in the pathophysiology of obsessive-compulsive disorder (OCD) due to its role in error processing, cognitive control and emotion regulation. OCD patients have shown altered concentrations in neurometabolites in the dACC, particularly Glx (glutamate+glutamine) and tNAA (N-acetylaspartate+ N -acetyl-aspartyl-glutamate). We investigated the immediate and prolonged effects of exposure and response prevention (ERP) on these neurometabolites. Glx and tNAA concentrations were measured using magnetic resonance spectroscopy (1H-MRS) in 24 OCD patients and 23 healthy controls at baseline. Patients received concentrated ERP over four days. A subset was re-scanned after one week and three months. No Glx and tNAA abnormalities were observed in OCD patients compared to healthy controls before treatment or over time. Patients with childhood or adult onset differed in the change over time in tNAA (F(2,40) = 7.24, ɳ2 p = 0.27, p = 0.004): concentrations increased between one week after treatment and follow-up in the childhood onset group (t(39) = -2.43, d = -0.86, p = 0.020), whereas tNAA concentrations decreased between baseline and follow-up in patients with an adult onset (t(42) = 2.78, d = 1.07, p = 0.008). In OCD patients with versus without comorbid mood disorders, lower Glx concentrations were detected at baseline (t(38) = -2.28, d = -1.00, p = 0.028). Glx increased after one week of treatment within OCD patients with comorbid mood disorders (t(30) = -3.09, d = -1.21, p = 0.004). Our OCD sample size allowed the detection of moderate to large effect sizes only. ERP induced changes in neurometabolites in OCD seem to be dependent on mood disorder comorbidity and disease stage rather than OCD itself. [ABSTRACT FROM AUTHOR]

Background: The dorsal anterior cingulate cortex (dACC) plays an important role in the pathophysiology of obsessive-compulsive disorder (OCD) due to its role in error processing, cognitive control and emotion regulation. OCD patients have shown altered concentrations in neurometabolites in the dACC, particularly Glx (glutamate+glutamine) and tNAA (N-acetylaspartate+N-acetyl-aspartyl-glutamate). We investigated the immediate and prolonged effects of exposure and response prevention (ERP) on these neurometabolites.Methods: Glx and tNAA concentrations were measured using magnetic resonance spectroscopy (1H-MRS) in 24 OCD patients and 23 healthy controls at baseline. Patients received concentrated ERP over four days. A subset was re-scanned after one week and three months.Results: No Glx and tNAA abnormalities were observed in OCD patients compared to healthy controls before treatment or over time. Patients with childhood or adult onset differed in the change over time in tNAA (F(2,40) = 7.24, ɳ2p= 0.27, p = 0.004): concentrations increased between one week after treatment and follow-up in the childhood onset group (t(39) = -2.43, d = -0.86, p = 0.020), whereas tNAA concentrations decreased between baseline and follow-up in patients with an adult onset (t(42) = 2.78, d = 1.07, p = 0.008). In OCD patients with versus without comorbid mood disorders, lower Glx concentrations were detected at baseline (t(38) = -2.28, d = -1.00, p = 0.028). Glx increased after one week of treatment within OCD patients with comorbid mood disorders (t(30) = -3.09, d = -1.21, p = 0.004).Limitations: Our OCD sample size allowed the detection of moderate to large effect sizes only.Conclusion: ERP induced changes in neurometabolites in OCD seem to be dependent on mood disorder comorbidity and disease stage rather than OCD itself. [ABSTRACT FROM AUTHOR]

Fucoidans, a diverse group of sulphated polysaccharides from brown algae, are biopolymers with many documented activities in vitro. While several factors are known to influence these activities, the degree of sulphation of the polymer is often regarded as a key parameter. The degree of sulphation on a biopolymer may be seasonally dependent, which, in turn, may affect the bioactivities of fucoidans. In this study, the effect of season and geographical location on the fucoidan sulphur content (as a proxy for degree of sulphation), was investigated. Crude fucoidan extracts were obtained using microwave- assisted extraction on eight different brown algae species, which were then analysed using elemental analysis. A significant seasonal dependence on the sulphur content in fucoidan extracts from Fucus serratus was observed. The difference in sulphur content between the investigated Fucus species is likely due to their different reproduction strategies. Of the eight species used in this study, Ascophyllum nodosum and Fucus evanescens contained the most sulphated fucoidans, while the species Dictyosiphon foeniculaceus contained lightly sulphated fucoidans. This suggests that species which thrive in saline waters may contain more sulphated fucoidans as a means of mitigating osmotic stress. No significant effects on the sulphur content in fucoidans from Fucus vesiculosus was observed between the three investigated countries. From these findings, it is apparent that seasonality is an important parameter, which must be considered for large scale production of highly sulphated fucoidans. [ABSTRACT FROM AUTHOR]

Use of telemedicine and remote monitoring technologies can significantly improve glycemic control in patients with type 1 diabetes and type 2 diabetes. Patients' ability to interact remotely with their health care providers via smartphones and other communication devices can increase their access to clinical care and online coaching and support programs. The establishment of metrics for clinical use of continuous glucose monitoring data and standardization of data reporting has enabled clinicians to maintain high-quality diabetes care through remote monitoring and telemedicine visits during the COVID-19 pandemic. This article discusses our experiences using remote monitoring and telemedicine visits during this time. [ABSTRACT FROM AUTHOR]

Background: The perioperative care and postoperative period after laparoscopic hernia repair have not been well described. The aim of this study was to describe the postoperative course after laparoscopic parastomal hernia repair.Methods: This was a prospective cohort study including consecutive patients undergoing laparoscopic parastomal hernia repair. The outcomes of interest were patient-reported pain, nausea and fatigue, time to stoma function, length of stay (LOS), use of transversus abdominis plane (TAP) block and epidural analgesia, the cumulative dose of morphine equivalent analgesics during the first 5 postoperative days, and postoperative complications.Results: Forty patients were included, 20% had ileostomy and 80% colostomy. The mesh was placed according to Sugarbaker (87.5%) and keyhole (12.5%) technique. Twenty-two patients (55%) required peripheral nervous blockades postoperatively. The median number of days to stoma function was 3 days (range 2-3.8). The mean cumulative dose of morphine equivalent analgesics was 21.9 mg on the day of surgery, 27.8 mg on the first postoperative day (POD1), 23.9 on POD2, 17.3 mg on POD3, 15.3 mg on POD4, 8.9 mg on POD5, and 115.2 mg in total. The median LOS was 4 days (range 3-6). The incidence of postoperative complications was 25%.Conclusion: Laparoscopic parastomal hernia repair carried a high risk of complications. Further, analgesic treatment after surgery was insufficient, with high opioid requirements postoperatively, and more than half of the patients required peripheral nervous blockades, indicating that postoperative pain is a major issue in this patient group. Improved postoperative care for these patients is required. [ABSTRACT FROM AUTHOR]

Herbivory has potential to modify vegetation responses to climatic changes. However, climate and herbivory also affect each other, and rarely work in isolation from other ecological factors, such as plant–plant competition. Thus, it is challenging to predict the extent to which herbivory can counteract, amplify, or interact with climate impacts on ecosystems. Here, we investigate how moose modify climatic responses of boreal trees by using experimental exclosures on two continents and modeling complex causal pathways including several climatic factors, multiple tree species, competition, tree height, time, food availability, and herbivore presence, density, and browsing intensity. We show that moose can counteract, that is, "cool down" positive temperature responses of trees, but that this effect varies between species depending on moose foraging preferences. Growth of preferred deciduous trees was strongly affected by moose, whereas growth of less preferred conifers was mostly driven by climate and tree height. In addition, moose changed temperature responses of rowan in Norway and balsam fir in Canada, by making fir more responsive to temperature but decreasing the strength of the temperature response of rowan. Snow protected trees from browsing, and therefore moose "cooling power" might increase should a warming climate result in decreased snow cover. Furthermore, we found evidence of indirect effects of moose via plant–plant competition: By constraining growth of competing trees, moose can contribute positively to the growth of other trees. Our study shows that in boreal forests, herbivory cooling power is highly context dependent, and in order to understand its potential to prevent changes induced by warming climate, species differences, snow, competition, and climate effects on browsing need to be considered. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of mealtime or post‐meal fast‐acting insulin aspart (faster aspart) vs mealtime insulin aspart (IAsp), both in combination with insulin degludec, in participants with type 1 diabetes (T1D). Methods: This multicentre, treat‐to‐target trial (Clinical trial registry: NCT02500706, ClinicalTrials.gov) randomized participants to double‐blind mealtime faster aspart (n = 342) or IAsp (n = 342) or open‐label post‐meal faster aspart (n = 341). The primary endpoint was change from baseline in HbA1c 26 weeks post randomization. All available information, regardless of treatment discontinuation, was used for evaluation of the effect. Results: Non‐inferiority for the change from baseline in HbA1c was confirmed for mealtime and post‐meal faster aspart vs IAsp (estimated treatment difference [ETD]: 95%CI, −0.02% [−0.11; 0.07] and 0.10% [0.004; 0.19], respectively). Mealtime faster aspart was superior to IAsp for 1‐hour PPG increment using a meal test (ETD, −0.90 mmol/L [−1.36; –0.45]; P < 0.001). Self‐monitored 1‐hour PPG increment favoured faster aspart at breakfast (ETD, −0.58 mmol/L [−0.99; −0.17]; P = 0.006) and across all meals (−0.48 mmol/L [−0.74; −0.21]; P < 0.001). Safety profiles and overall rate of severe or blood glucose‐confirmed hypoglycaemia were similar between treatments, but significantly less hypoglycaemia was seen 3 to 4 hours after meals with mealtime faster aspart. Conclusion: Mealtime and post‐meal faster aspart in conjunction with insulin degludec provided effective glycaemic control compared with IAsp, with no increased safety risk. Mealtime faster aspart provided PPG control superior to that of IAsp. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Deterioration in premorbid adjustment is related to ultra‐high risk (UHR) individuals developing psychosis, but it has not been examined how UHR individuals’ development differs compared to healthy controls. This study investigates differences in premorbid adjustment between UHR individuals and a healthy control group. Method: A total of 48 UHR individuals and 50 healthy controls matched on group level for age, gender and parents’ socio‐economic status were included in the study. Both groups were assessed with the Premorbid Adjustment Scale (PAS). Based on the PAS scores, composite social and academic scales were computed. Results: Compared to the healthy controls the UHR individuals’ social and academic premorbid adjustment declined across age periods. Social premorbid adjustment declined particularly between late adolescence and adulthood. Academic premorbid adjustment declined particularly between childhood and early adolescence. The UHR individuals had more premorbid adjustment difficulties on both the social and academic scale, and on the individual PAS scales. Conclusion: From childhood UHR individuals have lower levels of social and academic premorbid adjustment compared to healthy controls, and the difficulties increase with age. As such, social and academic premorbid adjustment could be an important focus for early intervention. [ABSTRACT FROM AUTHOR]

Recombinant factor VIIa (FVIIa) variants with increased activity offer the promise to improve the treatment of bleeding episodes in patients with inhibitor-complicated hemophilia. Here, an approach was adopted to enhance the activity of FVIIa by selectively optimizing substrate turnover at the membrane surface. Under physiological conditions, endogenous FVIIa engages its cell-localized cofactor tissue factor (TF), which stimulates activity through membranedependent substrate recognition and allosteric effects. To exploit these properties of TF, a covalent complex between FVIIa and the soluble ectodomain of TF (sTF) was engineered by introduction of a nonperturbing cystine bridge (FVIIa Q64C-sTF G109C) in the interface. Upon coexpression, FVIIa Q64C and sTF G109C spontaneously assembled into a covalent complex with functional properties similar to the noncovalent wild-type complex. Additional introduction of a FVIIa- M306D mutation to uncouple the sTF-mediated allosteric stimulation of FVIIa provided a final complex with FVIIa-like activity in solution, while exhibiting a two to three orders-of-magnitude increase in activity relative to FVIIa upon exposure to a procoagulant membrane. In a mouse model of hemophilia A, the complex normalized hemostasis upon vascular injury at a dose of 0.3 nmol/kg compared with 300 nmol/kg for FVIIa. [ABSTRACT FROM AUTHOR]

Conventional characterization and monitoring of hydrocarbon (HC) pollution is often expensive and time-consuming. Magnetic susceptibility (MS) has been proposed as an inexpensive, long-term monitoring proxy of the degradation of HC. We acquired repeated down hole MS logging data in boreholes at a HC-contaminated field research site in Bemidji, MN, USA. The MS data were analyzed in conjunction with redox conditions and iron availability within the source zone to better assess whether MS can serve as a proxy for monitoring HC contamination in unconsolidated sediments. The MS response at the site diminished during the sampling period, which was found to coincide with depletion of solid phase iron in the source zone. Previous geochemical observations and modeling at the site suggest that the most likely cause of the decrease in MS is the transformation of magnetite to siderite, coupled with the exhaustion of ferrihydrite. Although the temporal MS response at this site gives valuable field-scale evidence for changing conditions of iron cycling and stability of iron minerals it does not provide a simple proxy for long-term monitoring of biodegradation of hydrocarbons in the smear zone. [ABSTRACT FROM AUTHOR]

Even though reverse shoulder arthroplasty is a very successful procedure, painful complications occur. During the initial postoperative years, the most common reasons for pain are instability, postoperative fracture of the acromion or spine, and periprosthetic infection. Later, aseptic loosening, with humeral loosening being more frequent that glenoid loosening, can be a source of pain and reduction in function. A careful patient history, clinical examination, plain radiographs, computed tomography and blood tests give an explanation for the pain in most cases. The majority of these complications can be successfully treated, maintaining a functional reverse shoulder arthroplasty. However, if all examinations are normal, it is important to remember that nonshoulder conditions such as tumour of the lung or degenerative changes of the cervical spine can give shoulder pain. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin A1c is an excellent population health measure for the risk of vascular complications in diabetes, while continuous glucose monitoring (CGM) is a tool to help personalize a diabetes treatment plan. The value of CGM in individuals with type 1 diabetes (T1D) has been well demonstrated when compared with utilizing self-monitoring of blood glucose (SMBG) to guide treatment decisions. CGM is a tool for patients and clinicians to visualize the important role that diet, exercise, stress management, and the appropriate selection of diabetes medications can have in managing type 2 diabetes (T2D). Several diabetes organizations have recently reviewed the literature on the appropriate use of CGM in diabetes management and concluded CGM may be a useful educational and management tool particularly for patients on insulin therapy. The indications for using CGM either as a clinic-based loaner distribution model for intermittent use (professional CGM) or a CGM system owned by the patient and used at home with real-time glucose reading (personal CGM) are only beginning to be addressed in T2D. Most summaries of CGM studies conclude that having a standardized glucose pattern report, such as the ambulatory glucose profile (AGP) report, should help facilitate effective shared decision-making sessions. The future of CGM indications for the use of CGM is evolving rapidly. In some instances, CGM is now approved for making medication adjustments without SMBG confirmation and it appears that some forms of CGM will be approved for use in the Medicare population in the United States in the near future. Many individuals with T1D and T2D and their care teams will come to depend on CGM as a key tool for diabetes management. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin A1c is an excellent population health measure for the risk of vascular complications in diabetes, while continuous glucose monitoring (CGM) is a tool to help personalize a diabetes treatment plan. The value of CGM in individuals with type 1 diabetes (T1D) has been well demonstrated when compared with utilizing self-monitoring of blood glucose (SMBG) to guide treatment decisions. CGM is a tool for patients and clinicians to visualize the important role that diet, exercise, stress management, and the appropriate selection of diabetes medications can have in managing type 2 diabetes (T2D). Several diabetes organizations have recently reviewed the literature on the appropriate use of CGM in diabetes management and concluded CGM may be a useful educational and management tool particularly for patients on insulin therapy. The indications for using CGM either as a clinic-based loaner distribution model for intermittent use (professional CGM) or a CGM system owned by the patient and used at home with real-time glucose reading (personal CGM) are only beginning to be addressed in T2D. Most summaries of CGM studies conclude that having a standardized glucose pattern report, such as the ambulatory glucose profile (AGP) report, should help facilitate effective shared decision-making sessions. The future of CGM indications for the use of CGM is evolving rapidly. In some instances, CGM is now approved for making medication adjustments without SMBG confirmation and it appears that some forms of CGM will be approved for use in the Medicare population in the United States in the near future. Many individuals with T1D and T2D and their care teams will come to depend on CGM as a key tool for diabetes management. [ABSTRACT FROM AUTHOR]

This paper considers a parallel algorithm for Bayesian network structure learning from large data sets. The parallel algorithm is a variant of the well known PC algorithm. The PC algorithm is a constraint-based algorithm consisting of five steps where the first step is to perform a set of (conditional) independence tests while the remaining four steps relate to identifying the structure of the Bayesian network using the results of the (conditional) independence tests. In this paper, we describe a new approach to parallelization of the (conditional) independence testing as experiments illustrate that this is by far the most time consuming step. The proposed parallel PC algorithm is evaluated on data sets generated at random from five different real-world Bayesian networks. The algorithm is also compared empirically with a process-based approach where each process manages a subset of the data over all the variables on the Bayesian network. The results demonstrate that significant time performance improvements are possible using both approaches. [ABSTRACT FROM AUTHOR]

Adaptive approaches are required to counteract the mounting threats to water security. Demand management will feature centrally in such adaptations. The increase in the use of smart-meter technology offers an improved way for utilities to gauge consumer demand and to supply consumers with consumption feedback in (near) real time. Such feedback can decrease the discrepancies between perceived and actual water usage. In contrast to the energy sector, however, where the advantages associated with smart-meter consumption feedback are extensively documented, few studies have focused on the usefulness of such feedback when it comes to managing water consumption. This review assesses the evidence base for the effectiveness of water-usage feedback technology in encouraging water conservation. The review highlights the potential value of high-granularity smart-meter feedback technology in managing domestic water consumption. Findings from the papers covered in this review (N = 21) indicate that feedback was associated with decreases in water use of between 2.5 and 28.6%, with an average of 12.15% (SD = 8.75). A single paper reported a 16% increase in consumption associated with smart-meter feedback. The benefits for water utilities are highlighted, but the costs for utilities need to be considered further. Overall, more work is needed to conclusively pinpoint the most effective type of feedback in terms of information content and granularity, frequency of delivery and medium, and how water consumption is linked to energy consumption. This information is needed to make concrete recommendations to the water industry about the costs and benefits of investment in smart metering and consumer feedback. [ABSTRACT FROM AUTHOR]

In intensely cultivated regions, it is crucial to have knowledge of the leaching potential related to pesticides in agricultural production. This is especially true in countries, like Denmark, that base its drinking water supply on untreated groundwater. Since fluazifop-P-butyl (FPB) is applied to control perennial and annual weed grasses in agricultural fields, the objective of this study was to evaluate leaching of its two degradation products – fluazifop-P (FP; free acid; (R)-2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy)propionic acid) and TFMP (5-(trifluoromethyl)-2(1H)-pyridinone) – through an agricultural field consisting of loamy soil. Drainage and groundwater samples were collected over a five-year period following four spring/summer applications of FPB, and analysed for both FP and TFMP. FP was only detected once in groundwater, whereas TFMP within the first year after the first and fourth application was detected in concentrations exceeding the value of 0.1 μg L − 1 in 100% and 24% of the drainage samples and 9% and 14% of the groundwater samples, respectively. Detections of TFMP up to 18 months after application were obtained both in the drainage and groundwater. What differentiated the first and fourth FPB applications from the two others were heavy precipitation events within one week of FPB application, which resulted in rapid transport of TFMP through the discontinuities in the soil and contributed to relatively high TFMP detections in drainage and groundwater. This study indicated that pesticide degradates like TFMP, often being more soluble than the pesticide, have a relatively high leaching potential especially associated with heavy precipitation events shortly after the application. Hence, such pesticide degradates should like in Denmark be considered “relevant” meaning that the EU value for drinking water applies to them, having its leaching potential regulatory assessed based on high quality estimations of their persistence, and be exposed to an assessment of the risk to consumers of drinking contaminated groundwater. [ABSTRACT FROM AUTHOR]

AimThe major objectives of this study were to evaluate the existing pediatrics health care service provisions and utilizations of the public polyclinics in Barbados. Furthermore, the aim was to assess if the existing manpower resources were adequate.BackgroundBarbados has a mixed health care system consisting of both a socialized and a private health care system. The Ministry of Health commissioned a needs assessment survey of the pediatrics primary health care at the public polyclinics.MethodsPrimary data were collected through interviews with the public primary health care providers. Secondary data were collected from the Barbados Census Data and Ministry of Health statistics. Data were analyzed to assess the pediatrics primary health care service utilization and adequacy of existing resources at the polyclinics.FindingsIn 2012, there were 62 934 visits from children <16 years of age to the public polyclinics in Barbados and this accounted for 39.1% of all visits (both adults and children) to the polyclinics. An overall 16.7% of the visits were from children less than five years old to the Well Child Clinic for immunization and for growth and development monitoring; 32% of all physician consultations at the polyclinics were for children <16 years. Utilization of health services by children at the polyclinics was 5245 visits/month. Given an expected monthly demand for 10 822 visits from children, the polyclinics serve 48.5% of the primary health care demand for children in Barbados.ConclusionsThe public polyclinics play a pivotal role in the pluralistic primary health care system in Barbados. They fulfill nearly half of all the primary care demand and more importantly provides for almost the entire immunization demand, and thereby ensuring high coverage.The existing resources, if used optimally, would reduce the long consultation time observed in this setting, and thereby increase the capacity considerably. [ABSTRACT FROM PUBLISHER]

A new fossil cerambycid from Baltic amber, Dicentrus mehli sp. n. (Cerambycinae, Opsimini) is described and compared to extant congeners. This species is characterised by larger eyes, narrower inter-ocular space and shorter pedicle and, possibly, uniform colouring. This discovery allows confirming and pointing out the assumed hypotheses concerning the evolution of the Opsimini. In particular, the assumed association with fossil Calocedrus implies to dating the Baltic amber back to the Early Oligocene. [ABSTRACT FROM AUTHOR]

We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HLA-mismatched unrelated donors. The median age at transplantation was 12 months. Busulfan and cyclophosphamide was the most common conditioning regimen. Long-term survival was higher after HLA-matched sibling compared to alternative donor transplantation. There were no differences in survival after HLA-mismatched related, HLA-matched unrelated, or mismatched unrelated donor transplantation. The 5- and 10-year probabilities of survival were 62% and 62% after HLA-matched sibling and 42% and 39% after alternative donor transplantation (P = .01 and P = .002, respectively). Graft failure was the most common cause of death, accounting for 50% of deaths after HLA-matched sibling and 43% of deaths after alternative donor transplantation. The day-28 incidence of neutrophil recovery was 66% after HLA-matched sibling and 61% after alternative donor transplantation (P = .49). The median age of surviving patients is 7 years. Of evaluable surviving patients, 70% are visually impaired; 10% have impaired hearing and gross motor delay. Nevertheless, 65% reported performance scores of 90 or 100, and in 17%, a score of 80 at last contact. Most survivors >5 years are attending mainstream or specialized schools. Rates of veno-occlusive disease and interstitial pneumonitis were high at 20%. Though allogeneic transplantation results in long-term survival with acceptable social function, strategies to lower graft failure and hepatic and pulmonary toxicity are urgently needed. [ABSTRACT FROM AUTHOR]

A new species in the extant genus, Hydrotrupes Sharp, H. prometheus n. sp., (Coleoptera, Dytiscidae) is described from Baltic amber (Eocene) based on examination of a single female specimen. This description represents one of a limited number of diving beetle taxa described from fossiliferous amber and is currently the oldest known fossil assigned to Agabinae. Based on this specimen Hydrotrupes is at least 40 million years old. The occurrence of Hydrotrupes during the Eocene suggests that the current disjunct distribution of living Hydrotrupes species occurring in western North America and eastern China is a relict of former widespread distribution in the northern continents. Considering the age of this fossil and its similarity to living members of the genus Hydrotrupes, the conservation of morphology in this lineage of diving beetles is notable. Key morphological characters of the new species are illustrated, and the significance of this discovery for understanding Agabinae evolution and the biogeography of this previously hypothesized trans-Beringian lineage is discussed. [ABSTRACT FROM AUTHOR]

Background Pattern recognition control of prosthetic hands take inputs from one or more myoelectric sensors and controls one or more degrees of freedom. However, most systems created allow only sequential control of one motion class at a time. Additionally, only recently have researchers demonstrated proportional myoelectric control in such systems, an option that is believed to make fine control easier for the user. Recent developments suggest improved reliability if the user follows a so-called prosthesis guided training (PGT) scheme. Methods In this study, a system for simultaneous proportional myoelectric control has been developed for a hand prosthesis with two motor functions (hand open/close, and wrist pro-/supination). The prosthesis has been used with a prosthesis socket equivalent designed for normally-limbed subjects. An extended version of PGT was developed for use with proportional control. The control system's performance was tested for two subjects in the Clothespin Relocation Task and the Southampton Hand Assessment Procedure (SHAP). Simultaneous proportional control was compared with three other control strategies implemented on the same prosthesis: mutex proportional control (the same system but with simultaneous control disabled), mutex on-off control, and a more traditional, sequential proportional control system with co-contractions for state switching. Results The practical tests indicate that the simultaneous proportional control strategy and the two mutex-based pattern recognition strategies performed equally well, and superiorly to the more traditional sequential strategy according to the chosen outcome measures. Conclusions This is the first simultaneous proportional myoelectric control system demonstrated on a prosthesis affixed to the forearm of a subject. The study illustrates that PGT is a promising system training method for proportional control. Due to the limited number of subjects in this study, no definite conclusions can be drawn. [ABSTRACT FROM AUTHOR]

Research over the past quarter century has identified cyclin D-dependent kinases, CDK4 and CDK6, as the major oncogenic drivers among members of the CDK superfamily. CDK4/6 are rendered hyperactive in the majority of human cancers through a multitude of genomic alterations. Sustained activation of these protein kinases provides cancer cells with the power to enter the cell cycle continuously by triggering G1-S-phase transitions and dramatically shortening the duration of the G1 phase. It has also become clear, however, that CDK4/6 effectively counter cancer cell-intrinsic tumor suppression mechanisms, senescence and apoptosis, which must be overcome during cell transformation and kept at bay throughout all stages of tumorigenesis. As a central 'node' in cellular signaling networks, cyclin D-dependent kinases sense a plethora of mitogenic signals to orchestrate specific transcriptional programs. As the complexity of the cellular signaling network regulated by these oncogenic kinases unfolds, much remains to be learned about its architecture, its dynamics and the consequences of its perturbation. [ABSTRACT FROM AUTHOR]

Previous reviews of nutritional status in children under 5 years describe the Caribbean grouped with Latin America. This paper focuses specifically on the Caribbean and the goals and targets of the Millennium Declaration that have bearing on childhood development. The results indicate that CARICOM countries have made progress in terms of child health as assessed by gross health indicators. Yet, the millennium generation experiences coexistence of undernutrition and overweight in early childhood. The associations of GNI with markers such as poverty indices are somewhat inconsistent with traditional findings and highlight a need to reassess the causes of infantmortality and low birth weight. However, a lack of systematic local data has hampered progress on an individual country basis. Interventions that deal more pointedly with country specific needs are required including those targeting obesity if the MDGs are to be attained by all member states. [ABSTRACT FROM AUTHOR]

Incidentally discovered adrenal masses (incidentalomas) are common and present challenges both in diagnosis and management. When incidentally discovered adrenal masses are bilateral, a refined diagnostic approach is warranted since bilateral disease is more likely to be pathologic. We review a case of a 34-year-old man with incidentally discovered bilateral adrenal nodules. A comprehensive diagnostic strategy led to the diagnosis of bilateral pheochromocytoma caused by von Hippel-Lindau syndrome. He was successfully treated with bilateral laparoscopic adrenalectomy and has recovered well. While the initial diagnostic approach is similar to the unilateral incidentaloma, additional testing and/or genetic testing should be considered in the case of the bilateral adrenal mass. [ABSTRACT FROM AUTHOR]

Key articles and reviews were identified for the 2022 I ATTD Yearbook i and classified into one of four areas: diabetes epidemiology, diabetes therapy, diabetes technology, and primary care management of diabetes. Determining the Perception and Willingness of Primary Care Providers to Prescribe Advanced Di... I O'Donovan A SP 1 sp , Oser SM SP 1,2 sp , Parascando J SP 1 sp , Berg A SP 3 sp , Nease DE SP 2 sp , Oser TK SP 1,2 sp i I SP 1 sp Department of Family and Community Medicine, Penn State College of Medicine, Hershey, PA; SP 2 sp Department of Family Medicine, University of Colorado School of Medicine, Aurora, CO; SP 3 sp Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA i I J Patient Cent Res Rev 2021; i B I 8 i b I : 272-276 i Background Advances in diabetes technology such as insulin pumps and continuous glucose monitoring (CGM) devices have dramatically improved the management of diabetes. The prevalence of diabetes continues to increase; the most recent statistics from the International Diabetes Federation indicate that approximately 537 million adults are living with diabetes worldwide (1). Comments This is an exciting time in the area of diabetes management because the focus of the discussion between the primary care clinician and their patients can move from the importance of managing diabetes to a focus on diabetes remission. [Extracted from the article]

Dynamic methylations and demethylations of histone lysine residues are important for gene regulation and are facilitated by histone methyltransferases and histone demethylases (HDMs). KDM5B/Jarid1B/PLU1 is an H3K4me3/me2-specific lysine demethylase belonging to the JmjC domain-containing family of histone demethylases (JHDMs). Several studies have linked KDM5B to breast, prostate and skin cancer, highlighting its potential as a drug target. However, most inhibitor studies have focused on other JHDMs, and inhibitors for KDM5B remain to be explored. Here, we report the expression, purification and characterization of the catalytic core of recombinant KDM5B (ccKDM5B, residues 1-769). We show that ccKDM5B, recombinantly expressed in insect cells, demethylates H3K4me3 and H3K4me2 in vitro. The kinetic characterization showed that ccKDM5B has an apparent Michaelis constant (Kmapp) value of 0.5 μ m for its trimethylated substrate H3(1-15)K4me3, a considerably increased apparent substrate affinity than reported for related HDMs. Despite the presence of a PHD domain, the catalytic activity was not affected by additional methylation at the H3K9 position, suggesting that in vitro chromatin cross-talk between H3K4 and H3K9 does not occur for ccKDM5B. Inhibition studies of ccKDM5B showed both in vitro and in cell inhibition of ccKDM5B by 2,4-pyridinedicarboxylic acid (2,4-PDCA) with a potency similar to that reported for the HDM KDM4C. Structure-guided sequence alignment indicated that the binding mode of 2,4-PDCA is conserved between KDM4A/C and KDM5B. [ABSTRACT FROM AUTHOR]

Abstract: Identification of inhibitors of histone–lysine demethylase (HDM) enzymes is important because of their involvement in the development of cancer. An ELISA-based assay was developed for identification of inhibitors of the HDM KDM4C in a natural products library. Based on one of the hits with affinity in the low μM range (1, a catechol), a subset of structurally related compounds was selected and tested against a panel of HDMs. In this subset, two inhibitors (2 and 10) had comparable affinities towards KDM4C and KDM6A but no effect on PHF8. One inhibitor restored H3K9me3 levels in KDM4C transfected U2-OS cells. [Copyright &y& Elsevier]

ABSTRACT Cereals are major crops worldwide, and improvement of their nitrogen use efficiency is a crucial challenge. In this study proteins responding to N supply in barley roots and shoots were analysed using a proteomics approach, to provide insight into mechanisms of N uptake and assimilation. Control plants grown hydroponically for 33 d with 5 m m nitrate, plants grown under N deficiency (0.5 m m nitrate, 33 d) or short-term N starvation (28 d with 5 m m nitrate followed by 5 d with no N source) were compared. N deficiency caused changes in C and N metabolism and ascorbate-glutathione cycle enzymes in shoots and roots. N starvation altered proteins of amino acid metabolism in roots. Both treatments caused proteome changes in roots that could affect growth. Shoots of plants grown with ammonium as N source (28 d with 5 m m nitrate followed by 5 d with 5 m m ammonium) showed responses similar to N deficient shoots, characterized by turnover of ribulose 1·5-bisphosphate carboxylase/oxygenase (Rubisco) and increases in proteins of the chloroplastic transcription and translation machinery. Identified proteins in 67 and 49 varying spots in roots and shoots respectively, corresponded to 62 functions and over 80 gene products, considerably advancing knowledge of N responses in barley. [ABSTRACT FROM AUTHOR]

Aims: The aim was to demonstrate a method for automated image analysis of immunohistochemically stained tissue samples for extracting features that correlate with patient disease. We address the problem of quantifying tumor tissue and segmenting and counting cell nuclei. Materials and Methods: Our method utilizes a flexible segmentation method based on sparse coding trained from representative image samples. Nuclei counting is based on a nucleus model that takes size, shape, and nucleus probability into account. Nuclei clustering and overlays are resolved using a gray-weighted distance transform. We obtain a probability measure for pixels belonging to a nucleus from our segmentation procedure. Experiments are carried out on two sets of immunohistochemically stained images - one set based on the estrogen receptor (ER) and the other on antigen KI-67. For the nuclei separation we have selected 207 ER image samples from 58 tissue micro array-cores corresponding to 58 patients and 136 KI-67 image samples also from 58 cores. The images are hand-annotated by marking the center position of each nucleus. For the ER data we have a total of 1006 nuclei and for the KI-67 we have 796 nuclei. Segmentation performance was evaluated in terms of missing nuclei, falsely detected nuclei, and multiple detections. The proposed method is compared to state-of-the-art Bayesian classification. Statistical analysis used: The performance of the proposed method and a state-of-the-art algorithm including variations thereof is compared using the Wilcoxon rank sum test. Results: For both the ER experiment and the KI-67 experiment the proposed method exhibits lower error rates than the state-of-the-art method. Total error rates were 4.8 % and 7.7 % in the two experiments, corresponding to an average of 0.23 and 0.45 errors per image, respectively. The Wilcoxon rank sum tests show statistically significant improvements over the state-of-the-art method. Conclusions: We have demonstrated a method and obtained good performance compared to state-of-the-art nuclei separation. The segmentation procedure is simple, highly flexible, and we demonstrate how it, in addition to the nuclei separation, can perform precise segmentation of cancerous tissue. The complexity of the segmentation procedure is linear in the image size and the nuclei separation is linear in the number of nuclei. Additionally the method can be parallelized to obtain high-speed computations. [ABSTRACT FROM AUTHOR]

Abstract: To investigate ligand selectivity between the oncogenic KDM4C and tumor repressor protein KDM6A histone demethylases, KDM4C and KDM6A were enzymatically characterized, and subsequently, four compounds were tested for inhibitory effects. 2,4-dicarboxypyridine and (R)-N-oxalyl-O-benzyltyrosine (3) are both known to bind to a close KDM4C homolog and 3 binds in the part of the cavity that accommodates the side chain in position 11 of histone 3. The inhibition measurements showed significant selectivity between KDM4C and KDM6A. This demonstrates that despite very similar active site topologies, selectivity between Jumonji family histone demethylases can be obtained even with small molecule ligands. [Copyright &y& Elsevier]

Motivation: Detection of protein spots in two-dimensional gel electrophoresis images (2-DE) is a very complex task and current approaches addressing this problem still suffer from significant shortcomings. When quantifying a spot, most of the current software applications include a lot of background due to poor segmentation. Other software applications use a fixed window for this task, resulting in omission of part of the protein spot, or including background in the quantification. The approach presented here for the segmentation and quantification of 2-DE aims to minimize these problems.Results: Five sections from different gels are used to test the performance of the presented method concerning the detection of protein spots, and three gel sections are used to test the quantification of sixty protein spots. Comparisons with a state-of-the-art commercial software and an academic state-of-the-art approach are presented. It is shown that the proposed approach for segmentation and quantification of 2-DE images can compete with the available commercial and academic software packages.Availability: A command-line prototype may be downloaded, for non-commercial use, from http://w3.ualg.pt/~aanjos/prototypes.html.Contact: antoniodosanjos@gmail.comSupplementary information: Supplementary data are available at Bioinformtaics online. [ABSTRACT FROM AUTHOR]

Aims To review the current research of hidden populations of illicit drugs users using web-based methods and discuss major advantages and disadvantages. Methods Systematic review of 16 databases, including PubMed, PsycINFO (EBSCOhost), CSA Sociological Abstracts, Expanded Academic ASAP and Google Scholar. Findings Substances researched were most commonly ‘party/club drugs’ (such as ecstasy) and cannabis. All of the studies reviewed concluded that the internet is a useful tool for reaching hidden populations, but is likely to impose some bias in samples. Advantages include: access to previously under-researched target groups; speed; international applications; increased ease of data entry; and improved confidentiality for respondents. The major disadvantage is a lack of representativeness of samples. Conclusions Internet research is successful at accessing hidden populations of illicit drugs users, when appropriately targeted and provides unprecedented opportunities for research across a wide range of topics within the addictions field. Findings are unlikely to be generalisable to the general public, but appropriate for describing target populations. [ABSTRACT FROM AUTHOR]

Objectives. To examine utilization of the National AIDS Hotline of Trinidad and Tobago (AIDSLINE), evaluate its validity as a reliable data source for monitoring national HIV-related needs, and identify changes in caller requests between two different time periods. Methods. A total of 7 046 anonymous hotline calls in 1998-2002 (T1) and 2 338 calls in 2007 (T2) were analyzed for associations between caller characteristics and call content. A subsample of the data was also analyzed qualitatively. T1 findings were compared with HIV-related data collected by national policy-makers during that period, to evaluate the hotline's validity as a data source, and findings from T2, to reveal changes in call content over time. Results. In T1, the hotline was well utilized for information and counseling by both the general population and those living with HIV/AIDS. Call content from T2 indicated an increase versus T1 in 1) general awareness of HIV and other sexually transmitted diseases; 2) HIV testing; and 3) knowledge of HIV symptoms and transmission. HIV-related mental health needs, and the relationship between HIV and both child sexual abuse (CSA) and intimate partner violence (IPV), were identified as emerging issues. Conclusions. AIDSLINE is a well-utilized tool for providing information and counseling on national HIV-related issues, and a valid, cost-effective, easily accessed information source for planners and policy-makers involved in HIV management. Over the two study periods, there was an increase in HIV awareness and testing and in requests related to mental health, CSA, and IPV, but no change in sexual behaviors. [ABSTRACT FROM AUTHOR]

Background: Most human endogenous retroviruses (HERVs) invaded our genome at least 25 million years ago. The majority of the viral genes are degenerated, since no selection preserves them within the genome. However, a few intact and very old HERV genes exist, and likely are beneficial for the host. We here address evolutionary aspects of two HERV-V envelope genes, ENVV1 and ENVV2, located in tandem and containing a long open reading frame. Results: The ENVV2 gene is preserved with an intact reading frame during simian evolution, but none of the ENVV genes are found in the prosimian species tested. While we observe many transposon insertions in the gag and pol regions of the ERV-V2 provirus, the ENVV2 genes have escaped transposon crossfire in all species tested. Additional analysis of nucleotide substitutions provides further strong evidence of purifying selection on the ENVV2 gene during primate evolution. The other copy, ENVV1, seems to be involved in gene conversion of the major part of the envelope. Furthermore, ENVV1 and ENVV2 show placenta-specific expression in human and a baboon species. Conclusion: Our analyses show that ERV-V entered our genome after the split between simian and prosimian primates. Subsequent purifying selection and gene conversion have preserved two copies of the ENVV envelope gene in most species. This is the first case of gene conversion involving long open reading frames in HERVs. Together with the placenta-specific expression of the human and baboon ENVV1 and ENVV2 envelope genes, these data provide strong evidence of a beneficial role for the host. [ABSTRACT FROM AUTHOR]

The development of versatile Suzuki-Miyaura and Negishi cross-couplings with nonactivated alkenyl phosphates and aromatic boronic acids or organozinc reagents was achieved in acceptable to good yields. A series of 1,1-disubstituted alkenes were synthesized using a combination of either Ni(COD)2/Cy3P/K3PO4 or Pd2dba3/DPPF in THF. When working with alkenyl electrophiles in metal-catalyzed cross- couplings, this method lends itself as a less costly and more stable alternative to the corresponding triflate or nonaflate derivatives. In addition, initial studies are presented regarding an efficient 1,2-migration under Negishi coupling conditions. [ABSTRACT FROM AUTHOR]

A catalyst system was identified which promotes the Heck coupling of nonactivated vinyl phosphates with electron deficient alkenes providing a new entry to diene products from simple and readily accessible starting materials. In contrast to our earlier work exploiting P(t-Bu)3 as the ligand in the presence of PdCl2(COD), the application of Buchwald's dialkylbiarylphosphines, X-Phos, effectively promoted the vinylic substitution with a wide range of alkenyl phosphates in the presence of 10 equiv of lithium chloride. Importantly, these reaction conditions suppressed 1,2-migration of the alkenyl palladium(II) intermediate. Further studies are also reported with the catalytic system which encourages isomerization in order to determine the range of vinyl phosphates that may participate in these coupling reactions. The extent of the 1,2-migration was dependent on the C1-substituent where best results were noted for substrates possessing a C1-alkyl quaternary carbon. Hence, with certain members of this class of alkenyl phosphates either the migrated or nonmigrated Heck products may be preferentially synthesized by selection of the phosphine ligand. Finally, competition experiments between an unactivated aryl chloride and a vinyl phosphate with a palladium catalyst possessing either X-Phos or P(t-Bu)3 as ligand demonstrated the ability to carry out Heck coupling reactions selectively with the aryl halide. Oxidative addition of the metal catalyst into the aryl chloride bond rather than the C-O bond of the alkenyl phosphate is therefore preferred. [ABSTRACT FROM AUTHOR]

The metabolism of aerobic organisms continuously produces reactive oxygen species. Although potentially toxic, these compounds also function in signaling. One important feature of signaling compounds is their ability to move between different compartments, e.g. to cross membranes. Here we present evidence that aquaporins can channel hydrogen peroxide (H2O2). Twenty-four aquaporins from plants and mammals were screened in five yeast strains differing in sensitivity toward oxidative stress. Expression of human AQP8 and plant Arabidopsis TIP1;1 and TIP1;2 in yeast decreased growth and survival in the presence of H2O2. Further evidence for aquaporin-mediated H2O2 diffusion was obtained by a fluorescence assay with intact yeast cells using an intracellular reactive oxygen species-sensitive fluorescent dye. Application of silver ions (Ag+), which block aquaporin-mediated water diffusion in a fast kinetics swelling assay, also reversed both the aquaporin- dependent growth repression and the H2O2-induced fluorescence. Our results present the first molecular genetic evidence for the diffusion of H2O2 through specific members of the aquaporin family. [ABSTRACT FROM AUTHOR]

The microscopic electric polarization in terms of the dipole-dipole polarizability and its second hyperpolarizability of aligned films and ropes of carbon nanotubes has been studied theoretically by a point-dipole interaction model. The results show clearly the influence of intertube interactions on the microscopic polarization demonstrating the sensitivity of the electronic structure of carbon nanotubes to the surroundings. Both the polarizability and the second hyperpolarizability are screened due to the intertube interactions and deviate substantially from an additive model. It is noted that both the polarizability and the second hyperpolarizability reach their minimum values around the van der Waals separation. In the rope arrangement the polarizability of a tube is reduced by 10% and the second hyperpolarizability by as much as 50% as compared to an unperturbed tube. [ABSTRACT FROM AUTHOR]

Improving the performance of belief updating be- comes increasingly important as real-world Bayesian networks continue to grow larger and more complex. In this paper, an investigation is done on how variations over the message-computation algorithm of lazy propagation may impact its performance. Lazy propagation is a junction-tree-based inference algorithm for belief updating in Bayesian networks. Lazy propagation combines variable elimination (YE) with a Shenoy-Shafer message. passing scheme in an attempt to exploit the independence properties induced by evidence in a junction-tree-based algorithm. The authors investigate, the use of arc reversal (AR) and symbolic probabilistic inference (SPI) as alternative algorithms for computing clique-to-clique messages in lazy propagation. The paper presents the results of an empirical evaluation of the performance of lazy propagation using AR, SPI, and YE as the message-computation algorithm. The results of the empirical evaluation show that no single algorithm outperforms or is outperformed by the other two alternatives. In many cases, there is no significant difference in the performance of the three algorithms. [ABSTRACT FROM AUTHOR]

Homology models of plasma membrane H+-ATPase (Bukrinsky, J. T., Buch-Pedersen, M. J., Larsen, S., and Palmgren, M. G. (2001) FEBS Lett. 494,6–10) has pointed to residues in transmembrane segment M4 as being important for proton translocation by P-type proton pumps. To test this model, alanine-scanning mutagenesis was carried out through 12 residues in the M4 of the plant plasma membrane H+-ATPase AHA2. An I282A mutation showed apparent reduced H+ affinity, and this residue was subsequently substituted with all other naturally occurring amino acids by saturation mutagenesis. The ability of mutant enzymes to substitute for the yeast proton pump PMA1 was found to correlate with the size of the side chain rather than its chemical nature. Thus, smaller side chains (Gly, Ala, and Ser) at this position resulted in lower H+ affinity and lowered levels of H+ transport in vivo, whereas substitution with side chains of similar and larger size resulted in only minor effects. Substitutions of Ile-282 had only minor effects on ATP affinity and sensitivity toward vanadate, ruling out an indirect effect through changes in the enzyme conformational equilibrium. These results are consistent with a model in which the backbone carbonyl oxygen of Ile-282 contributes directly to proton translocation. [ABSTRACT FROM AUTHOR]

As the framework of probabilistic graphical models becomes increasingly popular for knowledge representation and inference, the need for efficient tools for its support is increasing. The Hugin Tool is a general purpose tool for construction, maintenance, and deployment of Bayesian networks and influence diagrams. This paper surveys the key functionality of the Hugin Tool and reports on new advances of the tool. Furthermore, an empirical analysis reports on the efficiency of the Hugin Tool on common inference and learning tasks. [ABSTRACT FROM AUTHOR]

Isoform GFAP∊ of the human cytoskeletal protein GFAP carries, as the result of alternative splicing of exon 7a of GFAP, a novel 42-amino-acid-long C-terminal region with binding capacity for the presenilin proteins. Here we show that exon 7a is present in a variety of mammals but absent from GFAP of chicken and fish. Comparison of the mouse and human GFAP exons showed an increased rate of nonsynonymous nucleotide substitutions in exon 7a compared to the other exons. This resulted in 10 nonconservative and 2 conservative amino acid substitutions and suggests that exon 7a has evolved under different functional constraints. Exons 7a of humans and higher primates are 100% identical apart from alanine codon 426, which is conserved in only 9% of the human alleles, while 21 and 70% of the alleles, respectively, have a valine or a threonine codon at that position. Threonine represents a potential phosphorylation site, and positive selection of that effect could explain the high allele frequency. [Copyright &y& Elsevier]

Heterozygous, de novo mutations in the glial fibrillary acidic protein (GFAP) gene were recently found to be associated with Alexander disease. We examined the functional effect of such mutations, and observed a decrease in GFAP dimerization. This effect behaves in a dominant fashion and points towards a potential mechanism in pathogenesis. [ABSTRACT FROM AUTHOR]