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Objective: To compare direct and indirect costs among caregivers of patients with major depressive disorder (MDD) and suicidal ideation and/or suicide attempts (MDSI) versus caregivers of patients with MDD alone versus caregivers of patients without MDD or suicidal ideation and/or suicide attempts (controls). Methods: Cohorts were based on caregivers of adult patients with MDSI, MDD alone, and controls. Patients were identified by Workpartners employer database ICD-9/ICD-10 codes (January 2010 to July 2019) and were spouses or domestic partners of employees (caregivers). Twenty controls and 20 MDD-alone caregivers were matched to each MDSI caregiver on sex, age, and index year. All caregiver-patient pairs had 6 months pre/postindex information and met additional inclusion/exclusion criteria. Patient and caregiver medical and prescription claims and caregiver absenteeism (payment/time) were analyzed. Direct costs (medical, prescription) and indirect costs (absence payments by benefit type) were analyzed using separate, 2-part stepwise regression models and controlling for demographics, job-related variables, region, index year, and Charlson Comorbidity Index score. Results: 570 MDSI caregiver-patient pairs and 11,400 matched MDD-alone and control pairs were identified. MDSI and MDD-alone caregivers had higher medical costs compared with controls ($5,131 and $4,548 versus $3,885, respectively; P

Background: In patients with pre-existing pulmonary hypertension undergoing surgery, there is an inherent risk of decompensation and right ventricular failure. Cemented hemi-arthroplasty in patients with pre-existing pulmonary hypertension predisposes them even more to morbidity and mortality from bone cement implantation syndrome (BCIS) with worsening of pulmonary hypertension. This risk should be recognized and steps taken for increased awareness, risk counselling and minimization of adverse effects. Case: We report a case of successful resuscitation of a patient with pre-existing pulmonary hypertension who developed 2 episodes of cardiac arrests—Grade 3 BCIS, shortly after cement implantation. Learning Points: Patients with pre-existing pulmonary hypertension for cemented hemi-arthroplasty are at additional risks and should be identified. Adequate risk counselling needs to be undertaken prior to surgery. A multi-disciplinary team effort is required. Discussion should be undertaken with the orthopaedic surgeon about the risks and benefits of using cemented implants. The anaesthetist needs to be vigilant for signs of BCIS, especially at the time of cement implantation and institute immediate resuscitation. Supportive treatment is the mainstay of management.

The lack of successful clinical trials in acute respiratory distress syndrome (ARDS) has highlighted the unmet need for biomarkers predicting ARDS mortality and for novel therapeutics to reduce ARDS mortality. We utilized a systems biology multi-“omics” approach to identify predictive biomarkers for ARDS mortality. Integrating analyses were designed to differentiate ARDS non-survivors and survivors (568 subjects, 27% overall 28-day mortality) using datasets derived from multiple ‘omics’ studies in a multi-institution ARDS cohort (54% European descent, 40% African descent). ‘Omics’ data was available for each subject and included genome-wide association studies (GWAS, n = 297), RNA sequencing (n = 93), DNA methylation data (n = 61), and selective proteomic network analysis (n = 240). Integration of available “omic” data identified a 9-gene set (TNPO1, NUP214, HDAC1, HNRNPA1, GATAD2A, FOSB, DDX17, PHF20, CREBBP) that differentiated ARDS survivors/non-survivors, results that were validated utilizing a longitudinal transcription dataset. Pathway analysis identified TP53-, HDAC1-, TGF-β-, and IL-6-signaling pathways to be associated with ARDS mortality. Predictive biomarker discovery identified transcription levels of the 9-gene set (AUC-0.83) and Day 7 angiopoietin 2 protein levels as potential candidate predictors of ARDS mortality (AUC-0.70). These results underscore the value of utilizing integrated “multi-omics” approaches in underpowered datasets from racially diverse ARDS subjects.

Background Comorbid anxiety is generally associated with poorer response to antidepressant treatment. This post hoc analysis explored the efficacy of esketamine plus an antidepressant in patients with treatment-resistant depression (TRD) with or without comorbid anxiety. Methods TRANSFORM-2, a double-blind, flexible-dose, 4-week study (NCT02418585), randomized adults with TRD to placebo or esketamine nasal spray, each with a newly-initiated oral antidepressant. Comorbid anxiety was defined as clinically noteworthy anxiety symptoms (7-item Generalized Anxiety Disorder scale [GAD-7] score ≥10) at screening and baseline or comorbid anxiety disorder diagnosis at screening. Treatment effect based on change in Montgomery-Asberg Depression Rating Scale (MADRS) total score, and response and remission were examined by presence/absence of comorbid anxiety using analysis of covariance and logistic regression models. Results Approximately 72% (162/223) of patients had baseline comorbid anxiety. Esketamine-treated patients with and without anxiety demonstrated significant reductions in MADRS (mean [SD] change from baseline at day 28: -21.0 [12.51] and -22.7 [11.98], respectively). Higher rates of response and remission, and a significantly greater decrease in MADRS score at day 28 were observed compared to antidepressant/placebo, regardless of comorbid anxiety (with anxiety: difference in LS means [95% CI] -4.2 [-8.1, -0.3]; without anxiety: -7.5 [-13.7, -1.3]). There was no significant interaction of treatment and comorbid anxiety (p = .371). Notably, in the antidepressant/placebo group improvement was similar in those with and without comorbid anxiety. Conclusion Post hoc data support efficacy of esketamine plus an oral antidepressant in patients with TRD, regardless of comorbid anxiety.

Undergraduates learn that gene editing in diverse organisms is now possible. How targeted manipulation of genes and genomes is utilized in basic science and biomedicine to address biological questions is challenging for undergraduates to conceptualize. Thus, we developed a lab experience that would allow students to be actively engaged in the full process of design, implementation of a gene editing strategy, and interpretation of results within an 8-week lab period of a Genetics course. The laboratory experience combines two transformative biotechnology tools; the utilization of green fluorescent protein (GFP) as a diagnostic marker of gene expression and the fundamentals and specificity of Clustered Regularly Interspaced Short Palindromic Repeats-cas9 (CRISPR-cas9) gene editing in bacterial cells. The students designed and constructed plasmids that express single guide RNA targeted to GFP, expressed the sgRNA and cas9 in bacteria cells, and successfully deactivated GFP gene expression in the bacterial cells with their designed CRISPR-cas9 tools. Student assessment revealed most students achieved student learning objectives. We conclude this lab experience is an effective and accessible method for engaging students in the scientific practices, knowledge and challenges revolving targeted CRISPR-cas9 gene manipulation. © 2019 International Union of Biochemistry and Molecular Biology, 47(2): 145-155, 2019.

Esketamine nasal spray (ESK) is indicated, in conjunction with an oral antidepressant (OAD), for the management of treatment-resistant depression (TRD) in adults. Select US-based patients from an open-label, long-term extension safety study of ESK (NCT02782104) participated in this study through semi-structured interviews. The study evaluated patient-reported early health changes related to emotional health, daily functioning, and social functioning in adults with TRD treated with ESK plus OAD. Eligible patients were responders to ESK who had begun initial ESK treatment ≤30 months before enrollment and were currently receiving ESK plus OAD. Results from 23 patients (9 men, 14 women; mean age, 46 years) were analyzed. Patients described the degree to which ESK treatment changed the effects of depression on aspects of health as either being much improved or improved (91.8%, 156/170). Key characteristics noted regarding treatment with ESK plus OAD included degree of effectiveness (n = 11), rapid onset of action (n = 7), and side-effect profile (n = 5). All patients reported being either satisfied (52%) or very satisfied (48%) with ESK plus OAD treatment. Adverse events were consistent with the known safety profile of ESK. Study insights may help prepare patients with TRD and their clinicians to anticipate potential health changes experienced with ESK.

Undergraduate biology students learn that gene editing is revolutionizing basic science and biomedicine. We developed lab experiences for mid-level undergraduate laboratory that actively engages st...

Acute kidney injury (AKI) continues to complicate cardiac operations. We sought to determine whether nadir oxygen delivery (DO2) on cardiopulmonary bypass (CPB) was a risk factor for AKI while also accounting for other postoperative factors.Using propensity scoring, we matched 85 patients who developed AKI after cardiac operations on CPB with 85 control patients who did not. We analyzed the following variables through midnight on postoperative day 1 (POD1): DO2, antibiotics, blood products and vasopressors (intraoperatively and postoperatively), and hemodynamic variables.Univariable analysis revealed AKI patients had lower nadir DO2 on CPB (208 vs 230 mL O2/min/m(2) body surface area, p = 0.03), lower intensive care unit admission blood pressure gradient across the kidney (mean arterial pressure minus central venous pressure; 60 vs 68 mm Hg; p0.001), a greater proportion of patients with mean arterial pressure of less than 60 mm Hg for more than 15 minutes in the postoperative period (70% vs 42%, p0.001), a greater chance of having a cardiac index of less than 2.2 (74% vs 49%, p = 0.02), and greater total vasopressor use through the end of POD1 (5.2 vs 2.3 mg, p = 0.002). On multivariable analysis, predictors of AKI were a DO2 on CPB of less than 225 mL O2/min/m(2) (odds ratio, 2.46; 95% confidence interval, 1.21 to 5.03; p = 0.01) and postoperative mean arterial pressure of less than 60 mm Hg for more than 15 minutes (odds ratio, 3.96; 95% confidence interval, 1.92 to 8.20; p0.001). An average postoperative pressor dose greater than 0.03 μg/kg/min did not reach significance (odds ratio, 1.98; 95% confidence interval, 0.95 to 4.11; p = 0.07).Postoperative hypotension on POD0 or POD1 and low DO2 on CPB both independently increase the AKI risk in cardiac surgical patients.

This case is based on an actual inventory accounting dilemma for a fish processing company located in Washington State. Rex Seafood, Incorporated (Rex) and its wholly owned subsidiary, Juneau Supply Company, purchase, process, and sell fish to restaurants and other retail outlets in the state of Washington and surrounding inland states. Rex has an agreement with Condor Enterprises to transport fish purchased from Juneau Supply in Alaska to Rex's facility in Washington for processing. The central issue of the case involves appropriate accounting and reporting for intercompany sales: How should the sales of inventory from Juneau Supply to Condor and the purchases by Rex from Condor be recorded and reported? Using the FASB Accounting Standards Codification, students must determine whether Rex's arrangement with Condor is a product financing arrangement, whether the purchases and sales of inventory should be considered a single exchange transaction, and whether the events should be considered intercompany transactions. In addition, students are asked to consider recording and disclosure implications of recommended solutions. This case is suitable for use in undergraduate Intermediate and graduate Financial Accounting classes.

Background/ContextIn response to a shortage of highly qualified teachers, states and school districts have enacted a number of policy innovations over the last two decades. While researchers have evaluated many of these reforms, little is known about the initial effectiveness of individuals with prior teaching assistant experience. We review existing literature related to teaching assistants and utilize administrative data to examine a number of characteristics of individuals who transition from work as teaching assistants to jobs as regular classroom teachers.Study PurposeIndividuals who become classroom teachers after having prior experience in schools working as teaching assistants may perform differently than other teachers due to additional exposure to classroom practices. The purpose of this study is to identify differences in the characteristics, effectiveness, and persistence of teachers who work as teaching assistants prior to entering the classroom as regular classroom teachers.PopulationWhile the population of focus varies somewhat across research questions, we generally focus on teachers with less than five years of experience working in elementary and middle school grades in all North Carolina public schools from 2005–2006 to 2009–2010. Additional data on teaching assistants employed from 2000–2001 to 2009–2010 in North Carolina public schools allows identification of individuals who had prior experience as teaching assistants in the state.Research DesignUsing administrative data records, we utilize quantitative descriptions of teacher characteristics and persistence to identify differences between teachers who entered the classroom with prior teaching assistant experience and other groups of teachers. For effectiveness comparisons, we estimate value-added models to compare the effectiveness of teachers in the identified groups of interest.Findings/ResultsOverall, we find that teachers who began as teaching assistants are (1) older, more racially diverse, lower-scoring on licensure exams, and more likely to enter the profession alternatively; (2) more effective in elementary-grades math and reading; and (3) more likely to remain as classroom teachers in North Carolina public schools.Conclusions/RecommendationsThese findings indicate that former teaching assistants represent a quality and highly persistent labor source and call for continued research to understand how additional exposure to classrooms benefits early-career teacher performance.

Aim Long-acting injectable antipsychotics (APs) are not well studied in recent-onset schizophrenia. This exploratory analysis of a study designed to reflect real-world schizophrenia, as defined by patients, interventions and outcomes, compared relative treatment effect between once-monthly paliperidone palmitate (PP) and daily oral APs in patients with recent-onset or chronic illness Methods This randomized, open-label, event monitoring board–blinded study compared treatment response in subjects with schizophrenia and a history of criminal justice system involvement following treatment with PP or oral APs for 15 months (ClinicalTrials.gov identifier, NCT01157351). Event-free probabilities were estimated using Kaplan–Meier method; hazard ratios (HRs) were estimated using Cox proportional hazard models. This subgroup analysis analysed data by disease duration (≤5 (recent-onset) or >5 years (chronic illness) since first psychiatric diagnosis). Results Seventy-seven subjects met the criteria for recent-onset illness; 365 for chronic illness. HRs (95% CI) for treatment failure for oral APs versus PP were 1.73 (0.87–3.45; P = 0.121) for recent-onset and 1.37 (1.02–1.85; P = 0.039) for chronic illness. Most common adverse events for PP versus oral APs were injection site pain (recent-onset, 26% vs. 0%; chronic, 17% vs. 0%), increased weight (14% vs. 6%; 12% vs. 6%), akathisia (14% vs. 9%; 10% vs. 7%), insomnia (12% vs. 17%; 18% vs. 10%) and anxiety (12% vs. 6%; 10% vs. 8%). Conclusions Although neither pre-planned nor adequately powered, the estimated HRs suggest that the relative advantage of PP over oral APs for reducing the risk for treatment failure may be greater in patients with recent-onset schizophrenia than in those with more chronic illness.

A food blog and a catering business provide an issue-rich context in which students examine tax issues involving individuals, a partnership, and a single owner LLC. The case illustrates how advances in technology and social media occur without the issuance of directly applicable tax guidance, thus introducing students to uncertainty in interpreting the tax law and providing professional advice. The goals of the case are to increase students' (1) abilities to identify tax issues for individuals and small home-based businesses, (2) tax research proficiency, (3) written communication skills, (4) technical knowledge, and (5) experience in tax planning. The case helps students develop four of the core competencies expressed in the AICPA's (2012) CPA Vision Project, including improving students' abilities to interpret converging information, think strategically and critically, communicate effectively, and adeptly use technology. Student responses to a posttest questionnaire indicate that the case helped develop their issue identification, tax research, and writing skills.

OBJECTIVE The Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study compared the effects of once-monthly paliperidone palmitate with daily oral antipsychotics on treatment failure in adults with schizophrenia. METHOD The PRIDE study is a 15-month, randomized, multicenter study (May 5, 2010, to December 9, 2013) of adult subjects with a DSM-IV diagnosis of schizophrenia and a history of incarceration. Subjects were randomly assigned to once-monthly paliperidone palmitate injections or daily oral antipsychotics (randomly assigned from 7 acceptable, prespecified oral antipsychotics) for 15 months. The primary end point was time to first treatment failure, defined as arrest/incarceration; psychiatric hospitalization; suicide; treatment discontinuation or supplementation due to inadequate efficacy, safety, or tolerability; or increased psychiatric services to prevent hospitalization. Time to first treatment failure was determined by a blinded event-monitoring board and analyzed with the Kaplan-Meier method. RESULTS In this study, 450 patients were randomly assigned, and 444 were included in the intent-to-treat population. Paliperidone palmitate was associated with significant delay in time to first treatment failure versus oral antipsychotics (hazard ratio, 1.43; 95% CI, 1.09-1.88; log rank P = .011). Observed treatment failure rates over 15 months were 39.8% and 53.7%, respectively. Arrest/incarceration and psychiatric hospitalization were the most common reasons for treatment failure in the paliperidone palmitate and oral antipsychotic groups (21.2% vs 29.4% and 8.0% vs 11.9%, respectively). The 5 most common treatment-emergent adverse events for the paliperidone palmitate treatment group were injection site pain (18.6% of subjects), insomnia (16.8%), weight increased (11.9%), akathisia (11.1%), and anxiety (10.6%). CONCLUSIONS In a trial designed to reflect real-world management of schizophrenia, once-monthly paliperidone palmitate demonstrated superiority compared to oral antipsychotics in delaying time to treatment failure. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT01157351.

Background Observational studies of switching from branded to generic formulations of the same drug substance often lack appropriate comparators for the subjects who switched. Three generic formulations were deemed equivalent to Concerta: an authorized generic (AG) identical except for external packaging, and two other generics (EG). Objective Compare the incidence of a combined endpoint (switching back to Concerta, changing the use of immediate release methylphenidate (MPH), stopping all long-acting methylphenidate, or starting a new medication) among people switched from Concerta to the AG versus the EG. Methods Cohort study from the Truven CCAE database of people aged 6 to 65 diagnosed with ADHD, treated with Concerta, and switched to the EG or to the AG formulation. Results In the EG arm 24.6% and in the AG arm 19.7% of subjects switched back to Concerta. The proportion of subjects meeting the combined endpoint was 39.5% in the EG arm, 32.9% in the AG arm, a crude risk ratio of 1.20 (95% CI 0.94, 1.54). After adjustment by propensity score stratification, the adjusted odds ratio (OR) was 1.23 (95% CI 0.90, 1.70). In an unplanned analysis using a different method of adjustment, the adjusted OR was 1.00 (95% CI 0.69, 1.44). Discussion This study did not detect a difference between the proportion of people who met the study endpoint in the two study arms, i.e. between those who switched to a generic formulation that was identical to Concerta except for external packaging and those who switched to the comparison generics. The high incidence of the combined endpoint in the AG arm demonstrates the need for an appropriate comparator in studies of this type. Trial registration ClinicalTrials.gov NCT02730572

A 15-year-old male with transposition of the great arteries presented with exertional chest pain. He was found to have a circumflex coronary artery from the neo-pulmonary artery that had not been transferred during his arterial switch operation. The circumflex coronary artery, fed through collaterals from a re-implanted single coronary artery, resulted in coronary steal. This report describes a management pathway to treat this rare anomaly.

ObjectiveThis analysis of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (NCT01157351) compared outcomes after administration of once-monthly paliperidone palmitate (PP) vs conventional oral antipsychotics (COAs) or atypical oral antipsychotics (AOAs).MethodsPRIDE was a 15-month study of 444 individuals with schizophrenia and a history of incarceration. They were randomly assigned to PP or to 1 of 7 commonly prescribed OAs. Primary endpoint was time to first treatment failure (TF). Event-free probabilities were estimated using the Kaplan–Meier method; treatment group differences (PP vs COAs, PP vs AOAs, and PP vs oral paliperidone/risperidone) were assessed using a log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No adjustment was made for multiplicity.ResultsCompared with PP, risk for first TF was 34% higher with COAs (HR: 1.34; 95% CI: 0.80–2.25), 41% higher with AOAs (HR: 1.41; 95% CI: 1.06–1.88), and 39% higher with paliperidone/risperidone (HR: 1.39; 95% CI: 0.97–1.99). Incidences of extrapyramidal symptom–related adverse events (AEs) were 45.7%, 13.7%, and 10.6% in the COA, AOA, and oral paliperidone/risperidone groups vs 23.9% in the PP group. Incidences of prolactin-related AEs were 5.7%, 3.8%, and 3.5% vs 23.5%, and incidences of ≥7% weight increase were 11.4%, 14.9%, and 16.0% vs 32.4%.ConclusionsResults suggest a lower risk of TF but a higher rate of some AEs after treatment with PP vs COAs, AOAs, and paliperidone/risperidone. Deselection of specific OAs and low patient-compliance rates with OAs likely biased the safety results.

Objectives Protecting the brain during cardiac surgery is a major challenge. We evaluated associations between nadir oxygen delivery (DO2) during paediatric cardiac surgery and a biomarker of brain injury, glial fibrillary acidic protein (GFAP). Methods Blood samples were obtained during a prospective, single-centre observational study of children undergoing congenital heart surgery with cardiopulmonary bypass (CPB) (2010-2011). Remnant blood samples, collected serially prior to cannulation for bypass and until incision closure, were analysed for GFAP levels. Perfusion records were reviewed to calculate nadir DO2. Linear regression analysis was used to assess the association between nadir DO2 and GFAP levels. Results A total of 116 consecutive children were included, with the median age of 0.75 years (interquartile range: 0.42-8.00) and the median weight of 8.3 kg (5.8-20.0). Single-ventricle anatomy was present in 19 patients (16.4%). Deep hypothermic circulatory arrest (DHCA) was used in 14 patients (12.1%). On univariable analysis, nadir DO2 was significantly associated with GFAP values measured during rewarming on CPB (P = 0.005) and after CPB decannulation (P = 0.02). On multivariable analysis controlling for CPB time, DHCA and procedure risk category, a significant negative relationship remained between nadir DO2 and post-CPB GFAP (P = 0.03). Conclusions Lower nadir DO2 is associated with increased GFAP levels, suggesting that diminished DO2 during paediatric heart surgery may be contributing to neurological injury. The DO2-GFAP relationship may provide a useful measure for the implementation of neuroprotective strategies in paediatric heart surgery, including goal-directed perfusion.

Background Children with Prader-Willi syndrome (PWS) have a predictable pattern of weight gain, with obesity beginning in early childhood and worsening as they get older and hyperphagia increases. Data on the most effective dietary modifications are scant and primarily anecdotal. As part of a longitudinal study investigating the natural history of PWS, we evaluated the effect of a well-balanced, energy-restricted diet on body composition and weight in young children with PWS.

Purpose – This paper seeks to explore the processes by which the offshoring of technology development to India and China by Western and Japanese multinationals has evolved from the localization/simplification of technology for local markets to the development of advanced technology in India and China for global markets. Design/methodology/approach – Case studies were developed based on 190 interviews conducted in China, India and several other countries. Respondents included multinational home country and offshore managers, as well as local entrepreneurs. Findings – Rather than following carefully thought out corporate strategies, the offshoring of technology development by multinationals is more often incremental and driven by the ambitions and expectations of Chinese and Indian entrepreneurs and managers. Meanwhile ‘‘technology competition’’ policies proposed in the USA and elsewhere are not taking sufficient account of the processes by which technology development is being offshored. Originality/value – Techno-nationalistic policies designed to allow one country to win a race with others in developing and monopolizing new technologies are increasingly dysfunctional. The identification of multinationals with ‘‘home countries’’ continues to weaken. At the same time, technologies and technology workers are more mobile than ever before. Better policies would allow nations to seek mutual benefit through today’s more globally dispersed technology development capabilities. Multinational managers in our study were not sufficiently accounting for the costs of offshoring and outsourcing technology, nor were they giving much thought to the longer term implications of their diminishing capabilities to develop or even control the development technology. More thought should be given to what aspects of technology constitute ‘‘core competencies’’ and which provide sustainable competitive advantage in the emerging global environment.

Prader-Willi syndrome (PWS) is a complex neurobehavioral condition which has been classically described as having two nutritional stages: poor feeding, frequently with failure to thrive (FTT) in infancy (Stage 1), followed by hyperphagia leading to obesity in later childhood (Stage 2). We have longitudinally followed the feeding behaviors of individuals with PWS and found a much more gradual and complex progression of the nutritional phases than the traditional two stages described in the literature. Therefore, this study characterizes the growth, metabolic, and laboratory changes associated with the various nutritional phases of PWS in a large cohort of subjects. We have identified a total of seven different nutritional phases, with five main phases and sub-phases in phases 1 and 2. Phase 0 occurs in utero, with decreased fetal movements and growth restriction compared to unaffected siblings. In phase 1 the infant is hypotonic and not obese, with sub-phase 1a characterized by difficulty feeding with or without FTT (ages birth-15 months; median age at completion: 9 months). This phase is followed by sub-phase 1b when the infant grows steadily along a growth curve and weight is increasing at a normal rate (median age of onset: 9 months; age quartiles 5-15 months). Phase 2 is associated with weight gain-in sub-phase 2a the weight increases without a significant change in appetite or caloric intake (median age of onset 2.08 years; age quartiles 20-31 months;), while in sub-phase 2b the weight gain is associated with a concomitant increased interest in food (median age of onset: 4.5 years; quartiles 3-5.25 years). Phase 3 is characterized by hyperphagia, typically accompanied by food-seeking and lack of satiety (median age of onset: 8 years; quartiles 5-13 years). Some adults progress to phase 4 which is when an individual who was previously in phase 3 no longer has an insatiable appetite and is able to feel full. Therefore, the progression of the nutritional phases in PWS is much more complex than previously recognized. Awareness of the various phases will aid researchers in unraveling the pathophysiology of each phase and provide a foundation for developing rational therapies. Counseling parents of newly diagnosed infants with PWS as to what to expect with regard to these nutritional phases may help prevent or slow the early-onset of obesity in this syndrome.

Objective. To assess effects of OROS methylphenidate on cognitive and academic tasks in 9 to 12 year olds with attention-deficit/hyperactivity disorder (ADHD). Methods. A double-blind, within-subject, crossover design was used to compare OROS methylphenidate with placebo in a laboratory classroom setting on several cognitive and academic tasks for 68 children who met randomization criteria. Results. Performance on the following measures was significantly better when children received individually optimized OROS methylphenidate than placebo: math fluency and accuracy measured by the Permanent Product Math Test, ADHD symptoms observed in the laboratory setting, computerized indices of attention and impulsivity as measured by the Test of Variables of Attention (TOVA), and visual—spatial working memory (Finger Windows Backwards). Study medication was well tolerated; adverse events were generally consistent with previous reports. Conclusions. OROS methylphenidate improves performance on measures of attention and vigilance, behavior, and working memory in a laboratory school setting in 9 to 12 year olds with ADHD.

Support for multicast services is crucial for content distribution in mobile wireless networks (MWNs). Efficient multicasting in MWNs faces challenges not encountered in other types of networks such as the mobility of nodes, the tenuous status of communication links, limited resources, and indefinite knowledge of the network topology. This paper addresses these challenges by providing a framework and architecture with proactive and reactive components to support multicasting in MWNs emphasizing reliability and efficiency of end-to-end packet delivery. The architecture includes the Robust Multicast Routing protocol (RoMR) to provide efficient multicast services for content distritbution MWNs. RoMR's architecture includes a proactive and reactive component. The proactive component calculates multiple multicast trees based on the prediction of future availability of the links and the assumption that the trees will become disconnected over time. The reactive components respond to changes in the network topology due to the mobility of the nodes and to changes in the multicast group's membership. The novelty of the proposed protocol stems from integrating techniques that have not previously been combined into a multicasting protocol and a unique method to calculate the relative weights of the links. In addition to the specifications of the protocol, a simulation framework was developed to test different implementations of the various components of RoMR. Simulations compared the performance of the basic version of RoMR to a version that ignored link weights, and to the Multicast Optimized Link State Routing (MOLSR) protocol, a source tree-based, topology-aware multicast protocol. A statistical analysis of the results showed that RoMR performed better, overall, than the other two protocols. Copyright © 2010 John Wiley & Sons, Ltd.

Large-scale changes to the world's ecosystem are resulting in the deterioration of biostructure—the complex web of species interactions that make up ecological communities. A difficult, yet crucial task is to identify food web structures, or food web motifs, that are the building blocks of this baroque network of interactions. Once identified, these food web motifs can then be examined through experiments and theory to provide mechanistic explanations for how structure governs ecosystem stability. Here, we synthesize recent ecological research to show that generalist consumers coupling resources with different interaction strengths, is one such motif. This motif amazingly occurs across an enormous range of spatial scales, and so acts to distribute coupled weak and strong interactions throughout food webs. We then perform an experiment that illustrates the importance of this motif to ecological stability. We find that weak interactions coupled to strong interactions by generalist consumers dampen strong interaction strengths and increase community stability. This study takes a critical step by isolating a common food web motif and through clear, experimental manipulation, identifies the fundamental stabilizing consequences of this structure for ecological communities.

The purpose of this teaching case is to expand students' understanding of the concepts of professional skepticism and independence. The case is based on an actual incident and illustrates the exercise of professional skepticism by a staff auditor who finds himself in the uncomfortable situation of accusing a friend of fraud. The case demonstrates the difficult personal and professional choices that auditors must sometimes make. In analyzing the case, students consider auditor independence rules, as well as the concepts of independence in appearance and independence in mental attitude. Students are asked to identify the types of audit evidence and internal controls needed to detect and prevent the fraud, and to consider the appropriate audit response to an adverse situation.

The prevalence of pediatric obesity has greatly increased over the past several decades, affecting both males and females among all racial and ethnic groups, and bringing with it comorbidities that were only observed in adults in the past. Childhood obesity is the most alarming public health issue facing the world today. Lifestyle modifications to reverse obesity are considered the cornerstone of treatment, but compliance is often poor and results may be minimal. Thus, many adolescents are turning to bariatric surgery as a treatment for obesity and its complications. The long-term success rate, consequences and risks for the pediatric population are still unknown, as is the compliance rate with the necessary dietary modifications that are required after these procedures.

During the boom of the 1990s, Computone Corporation was a high-tech company with viable hardware and software products. The company struggled financially, however, in this very competitive industry. This case demonstrates how the company employed earnings manipulation techniques that resulted in violations of GAAP through improper revenue recognition. Developed from SEC Enforcement Releases, the case demonstrates the SEC's willingness to prosecute corporations and individuals involved in fraudulent financial reporting. The case requires you to analyze the impact of improper revenue recognition on financial statements and to identify risk factors that may have provided incentive and opportunity to engage in fraudulent financial reporting. In addition, the case asks you to consider the potential effect of the Sarbanes-Oxley Act of 2002 and discuss corporate governance issues.

Conduct a cost effectiveness analysis for the Paliperidone palmitate Research In Demonstrating Effectiveness (PRIDE) trial.PRIDE was a 15 month, prospective, randomized, open-label study in which once monthly paliperidone palmitate significantly delayed the time to first treatment failure (healthcare or criminal justice system [HC/CJS] events) versus oral antipsychotics in recently incarcerated adults with schizophrenia. The present analysis used a state government perspective and HC/CJS event data that were collected on a resource use questionnaire (RUQ) every 3 months.Since cost information was not collected in the trial, cost estimates from published literature and an analysis of multistate Medicaid data for CJS and HC events, respectively, were applied to RUQ event data. Effectiveness and costs were adjusted to 456 days (trial duration). Incremental cost effectiveness was calculated as the adjusted cost difference divided by the adjusted effectiveness difference.Adjusted costs (in US dollars) in the paliperidone palmitate group (n = 198) and the oral antipsychotic group (n = 193), respectively, were: non-drug costs $22,331 and $25,027; drug costs $18,592 and $7833; and total costs $40,923 and $32,860. Adjusted effectiveness differences and corresponding incremental cost effectiveness per event avoided (in parentheses) for paliperidone palmitate versus oral antipsychotics were as follows: 0.33 fewer CJS events ($24,409), 0.13 fewer psychiatric hospitalizations ($60,484), 0.46 fewer psychiatric hospitalizations or CJS events combined ($17,391), and 0.30 fewer incarcerations ($26,754).Costs for HC/CJS events avoided offset 25% of the greater drug cost for the paliperidone palmitate versus oral antipsychotic treatment group in this vulnerable population. Use of a recall-dependent RUQ for event rates and cost estimates instead of actual costs are potential limitations and may make the results conservative from a state government perspective. Indirect costs are likely to be substantial for this population, but were not considered in the analysis.

In the 1980s and early 1990s, major US government studies and popular press reports argued that Japanese firms were about to take the lead in the biotechnology industry, following a pattern established in the semiconductor and other industries where large Japanese firms had led the way in commercializing radically new technologies such as the transistor. The Japanese model included coordination by the Ministry of International Trade and Industry (MITI) or, occasionally, other ministries. New technology was often developed by government-subsidized research cooperatives made up of leading firms. Large firms commercialized the new technology, supported by financing from keiretsu banks and the development of complementary technologies by partner firms. If start-up firms in the US or elsewhere developed relevant technologies, the Japanese bought them. It soon became clear, however, that the US model, linking universities, venture capital-backed start-ups, and large firms, was outperforming the Japanese model in biotechnology. The Japanese undertook reforms to make their system more like that of the US. This paper describes these changes and makes a preliminary assessment of their success.

This study evaluates the usefulness of a multidimensional conceptualization of organizational commitment in the public accounting environment and examines the influence of mentoring relationships on each of these dimensions. An integrated examination of antecedent variables for each of the dimensions of organizational commitment, as well as the consequence of intention to leave the public accounting organization, was conducted. Results suggest that while organizational commitment in the public accounting environment can be conceptualized in terms of affective, moral and economic attachment to the firm, affective commitment is the most descriptive of these constructs. While mentoring relationships have a positive impact on each of the dimensions of commitment, affective commitment is most influenced. Affective commitment in the public accounting workplace develops as a result of distinct antecedent experiences and has direct implications for the consequence of interest and intentions to leave.

Heroin detoxification by anesthesia-assisted rapid opiate detoxification (AAROD) can be achieved in approximately 1 hour using intravenous administration of midazolam, propofol, and naloxone. Opiate dependence and detoxification techniques are reviewed. Important aspects of patient care and perianesthesia nursing are described using a case study. To assist in caring for the patient undergoing anesthesia-assisted rapid opiate detoxification, the perianesthesia nurse should understand the methodology and controversy of this new procedure.

(2007). The Real Global Technology Challenge. Change: The Magazine of Higher Learning: Vol. 39, No. 4, pp. 11-13.

Background Public health considerations require that clinical trials address the complex "real-world" needs of patients with chronic illnesses. This is particularly true for persons with schizophrenia, whose management is frequently complicated by factors such as comorbid substance abuse, homelessness, and contact with the criminal justice system. In addition, barriers to obtaining health care in the United States often prevent successful community reentry and optimal patient management. Further, nonadherence to treatment is common, and this reinforces cycles of relapse and recidivism. Long-acting injectable antipsychotic therapy may facilitate continuity of treatment and support better outcomes, particularly in patients who face these challenges. Clinical trials with classical explanatory designs may not be the best approaches for evaluating these considerations. We describe the design and rationale of a novel trial that combines both explanatory and pragmatic design features and studies persons with schizophrenia who face these challenges. Design and rationale The Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study is a prospective, open-label, randomized, 15-month study conducted between May 5, 2010, and December 9, 2013, comparing long-acting injectable paliperidone palmitate and oral antipsychotic medications in subjects with schizophrenia (according to DSM-IV criteria). Investigators and subjects had broad flexibility for treatment decision-making, thus making it a model that better reflects real-world practice. The primary end point was time to treatment failure, defined as arrest/incarceration psychiatric hospitalization; suicide; treatment discontinuation or supplementation due to inadequate efficacy, safety, or tolerability; or increased psychiatric services to prevent hospitalization. This end point was adjudicated by a blinded event monitoring board. Patients were followed to the 15-month end point, regardless of whether they were maintained on their initial randomized treatment. This article provides some of the reasoning behind the authors' choices when combining features from both explanatory and pragmatic approaches to this trial's design. Conclusions The PRIDE study incorporates real-world design features in a novel, prospective, comparative study of long-acting injectable and oral antipsychotics in persons with schizophrenia who have had recent contact with the criminal justice system. Insights provided should help the reader to better understand the need for more real-world approaches for clinical studies and how a broader approach can better aid clinical treatment and public health decision-making. Trial registration ClinicalTrials.gov identifier: NCT01157351.

The technological innovation and diffusion literatures consistently suggest the importance of the institutional environment, including non-market as well as market organizations and relationships, in the commercialization of innovation. There is, however, no general framework for studying the relevant organizations and relationships as a structured system. This paper draws on organizational ecology to develop such a framework, ‘the innovation community’. The paper then suggests how the new framework could be employed in guiding research and in developing a general institutional theory of technology commercialization.

Five multinucleate opalinids from Canada and Cameroon, Africa, commensal in anuran amphibians, are redescribed. The relative size of the falx and the presence or absence of a posterior zone of convergence of kineties in silver-impregnated specimens support three new combinations: Cepedea sudafricana (Fantham, 1923), Cepedea virguloidea (Metcalf, 1923), and Cepedea obtrigonoidea (Metcalf, 1923). These new combinations suggest that Cepedea may be a much more common genus in the Nearctic region than was previously realized.

Placebo and pharmacodynamic (PD) models were developed which link temporal measures of efficacy in children with attention deficit hyperactivity disorder (ADHD) and methylphenidate (MPH) plasma concentrations from adults. These models can be used to predict daily pediatric clinical measure profiles following administration of different MPH formulations in children without conducting pediatric pharmacokinetic (PK) or PD studies by using more easily obtained adult PK data. Mean PK data from various extended-release MPH formulations studied in adults and mean PD data from nine pediatric efficacy studies were obtained from the literature. The individual time-course of the clinical measures from three pediatric trials were also analyzed after being combined with the meta-analysis data. The clinical measure profiles following placebo administration were described by indirect response models with time-varying elimination rates. MPH pharmacodynamic effect was described by E(max) models, which included time-dependent tolerance. Internal and external evaluations using a visual predictive check technique confirmed the prediction capability of the models. This modeling exercise demonstrated that time courses of MPH concentrations in adults with different drug release patterns can be used to predict time courses of clinical efficacy parameters in pediatrics by employing the models developed by meta-analysis.

Attention deficit/hyperactivity disorder (ADHD) is estimated to affect 4-5% of adults. Impairment across multiple domains of daily living can be mild to serious. OROS methylphenidate (MPH) was evaluated in two large adult clinical trials, and in 2008 it was approved in the USA to treat ADHD in adults aged up to 65 years.Products approved for adult ADHD; chemistry, pharmacodynamics, pharmacokinetics, metabolism, efficacy, safety, tolerability, abuse liability, regulatory affairs, and relative merits and limitations associated with OROS MPH; and complexities associated with diagnosis and treatment of ADHD are discussed in this review. The reader will gain an introduction to the epidemiology, features and special issues regarding clinical management of ADHD in adults. Key features and development of OROS MPH are presented, and unique characteristics of the delivery system and their implications for clinical use of the drug are discussed.The OROS system delivers MPH in a highly consistent manner using osmotic pressure at a controlled rate over a 12-h duration of effect. Compared with immediate-release MPH, it provides a smoother pharmacokinetic curve, and it may show greater patient compliance, fewer missed doses and reduced abuse liability.

The article reviews the book Remade in America: Transplanting & Transforming Japanese Management Systems, edited by Jeffrey K. Liker, W. Mark Fruin and Paul S. Adler.

Marketing implications of technological innovation have received considerable attention in the recent past. In this article, Mohan Reddy, John Aram, and Leonard Lynn suggest that the institutional scope for understanding technology diffusion, in addition to supplier and user organizations and industries, should include organizations that manufacture technological complementarities, institutions that possess vertical complementary assets, and the nonmarket sector. The nonmarket sector includes trade associations, professional societies, governmental agencies, independent research agencies, and public service organizations. The authors develop a set of propositions and discuss the implications of our framework for marketers of technical products.

This paper describes an application of terrain analysis where a national dataset of landform elements derived from a 25 m resolution national digital terrain model has been used to underpin soil-landscape modelling in the complex steepland terrain of New Zealand. This research supports S-map, a new initiative to improve New Zealand’s soil databases. Landform elements are derived from a fuzzy classification based on local geometry (curvature and slope) and landscape context, and provide a primary foundation for mapping soil distribution in steepland land systems, which significantly improves knowledge of soil distribution on hillslopes in complex landscapes, and over a wide range of land systems. So far, land elements and soil-landscape models have been used to model soil distribution in more than 10 distinct land systems (covering over 10% of New Zealand’s total steeplands area).

Bedside microcomputer-derived, minute-to-minute mean arterial pressure (MAP) values during the first 48 hours of life were studied in 100 preterm babies with birth weight less than or equal to 1500 gm. In those babies (n = 72) with no periventricular-intraventricular hemorrhage (PV-IVH) or with grade 1 PV-IVH, the MAP values increased during the study period, with minute-to-minute variation and interval undulation. The MAP values in those with birth weight greater than 1000 gm were higher than in those of lower birth weight. Infants in whom grades 2 to 4 PV-IVH developed (n = 28) had consistently lower MAP values during the study period. Minute-to-minute variability, expressed as the average of the coefficients of variation at 15-minute intervals, did not differ between birth weight groups, nor did they differ between the PV-IVH group and their matched control subjects. However, those with PV-IVH spent a greater percentage of time, with a coefficient of variation greater than or equal to 13% or less than 3%, than their matched control subjects spent (p less than 0.005). This study provides reference data for MAP changes in premature babies. The observed MAP changes in those with PV-IVH lend support to a significant role for MAP alterations in the pathogenesis of PV-IVH.

The blood pressure (BP) and transcutaneous Po2, (TcPo2) changes associated with intensive care procedures were evaluated to determine whether responses differ between babies with and without periventricular-intraventricular hemorrhage (PV-IVH). Fifty-three inborn babies ≤1500 g were studied using a microcomputer-based monitoring system. With almost any procedure including a seemingly benign one such as a diaper change, peak systolic BP increased and TcPo2 decreased. However, responses to interventions did not differ between babies with PV-IVH and those without PV-IVH. Neither did these responses differ between those with birth weight ≤1000 g and >1000 g. When each baby's record was scanned for the highest peak systolic BP before diagnosis of PV-IVH or within 48 hours in those with no PV-IVH and their BP points plotted against birth weight, a stable region was evident wherein PV-IVH occurred at a lower incidence (13%). When peak systolic BP was beyond this stable region, the incidence of PV-IVH was significantly higher, 70% (P < .0001). The stability boundary for the maximum systolic BP is birth weight-dependent; the limit for the highest tolerable peak systolic BP is lower for the low-birth-weight infant. In over 70% of instances the highest peak systolic BP was associated with motor activities either induced by nursery procedures or spontaneous. We speculate that decreasing the frequency of intensive care interventions may decrease episodic BP increases to levels beyond the birth weight-dependent stability boundary where PV-IVH is likely to occur.

The molecular diversity of rumen methanogens in feedlot cattle and the composition of the methanogen populations in these animals from two geographic locations were investigated using 16S rRNA gene libraries prepared from pooled PCR products from 10 animals in Ontario (127 clones) and 10 animals from Prince Edward Island (114 clones). A total of 241 clones were examined, with Methanobrevibacter ruminantium accounting for more than one-third (85 clones) of the clones identified. From these 241 clones, 23 different 16S rRNA phylotypes were identified. Feedlot cattle from Ontario, which were fed a corn-based diet, revealed 11 phylotypes (38 clones) not found in feedlot cattle from Prince Edward Island, whereas the Prince Edward Island cattle, which were fed potato by-products as a finishing diet, had 7 phylotypes (42 clones) not found in cattle from Ontario. Five sequences, representing the remaining 161 clones (67% of the clones), were common in both herds. Of the 23 different sequences, 10 sequences (136 clones) were 89.8 to 100% similar to those from cultivated methanogens belonging to the orders Methanobacteriales , Methanomicrobiales , and Methanosarcinales , and the remaining 13 sequences (105 clones) were 74.1 to 75.8% similar to those from Thermoplasma volcanium and Thermoplasma acidophilum . Overall, nine possible new species were identified from the two clone libraries, including two new species belonging to the order Methanobacteriales and a new genus/species within the order Methanosarcinales . From the present survey, it is difficult to conclude whether the geographical isolation between these two herds or differences between the two finishing diets directly influenced community structure in the rumen. Further studies are warranted to properly assess the differences between these two finishing diets.