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Block of neuronal apoptosis by a sustained increase of steady-state free Ca2+ concentration.

Programmed death is a ubiquitous feature of the development of the vertebrate nervous system. This death is prevented in vivo by trophic factors and by afferent input. Death of neurons can also be prevented in culture models of programmed death by trophic factors and by chronic depolarization with elevated concentrations of K+ in the culture medium. The latter effect is mediated by Ca2+ influx through voltage-gated channels and may prevent death by mimicking survival-promoting effects of naturally occurring electrical activity. Little is currently known about the mechanism by which either trophic factors or increased cytoplasmic Ca2+ promote survival.

Animals↗

Discordance between ambulatory monitoring and programmed stimulation in assessing efficacy of class IA antiarrhythmic agents in patients with ventricular tachycardia.

Concordance between programmed stimulation and 24 hour ambulatory electrocardiographic (Holter) monitoring was studied in 54 patients with sustained ventricular tachycardia during 84 therapeutic trials with class IA antiarrhythmic agents. During baseline studies before treatment, all patients had frequent (greater than or equal to 30/h) ventricular premature complexes on Holter recordings and sustained ventricular tachycardia inducible by one to three extrastimuli. During treatment, programmed stimulation and Holter monitoring were repeated. Efficacy of treatment determined by programmed stimulation (ventricular tachycardia no longer inducible or nonsustained) was compared with three Holter criteria of efficacy: I = 83% or more reduction of ventricular premature complexes and abolition of ventricular tachycardia; II = 50% or more reduction of ventricular premature complexes and 90% or more reduction of couplets and abolition of ventricular tachycardia; III = abolition of ventricular tachycardia in patients with ventricular tachycardia during a baseline Holter recording. Treatments were judged effective by programmed stimulation criteria in only 25% of cases but in 51, 63 and 75% of cases by Holter criterion I, II and III, respectively. Results of programmed stimulation and Holter monitor were discordant (effective by one criterion but ineffective by the other) in 50% of cases using Holter criterion I, in 54% using Holter criterion II and in 61% using Holter criterion III. In the majority of discordant results, treatments appeared efficacious by Holter criteria but ineffective by programmed stimulation criteria, suggesting insensitivity of efficacy by Holter criteria or nonspecificity of induced ventricular tachycardia during treatment, or both.

Aged↗

The Newfoundland and Labrador Heart Health Program dissemination story: the formation and functioning of effective coalitions.

Newfoundland and Labrador is the most easterly province of Canada (O'Loughlin et al., Figure 1) with a population of 537,000. Rural in nature, 50% of the population resides in widely-dispersed communities of less than 2500 people. The economy traditionally relied on the fishing industry, but with the closure of the once lucrative cod fishery in 1991, the poorest province in Canada faced a difficult economic climate with up to 20% unemployment rates. With little funding available to supplement or sustain expensive initiatives, the Demonstration Phase of the Newfoundland and Labrador Heart Health Program (1990-1996) focused on how community-based programs are developed and sustained, with a view to diffusion throughout the province. The whole province was defined as the demonstration site for the project, and a community mobilization strategy was used with extensive reliance on community health professionals and volunteer contributions.

Cardiovascular Diseases↗

Long-term follow-up of cardiovascular disease risk factors in children after an obesity intervention.

BACKGROUND: Data concerning the long-term improvement of cardiovascular disease (CVD) risk factors after an obesity intervention in children are limited. OBJECTIVE: We studied changes in weight status and CVD risk factors in children in an intervention program and evaluated whether these changes were sustained 1 y after the end of the intervention. DESIGN: We analyzed changes in the SD score (SDS) of body mass index [BMI; in kg/m2 (SDS-BMI)], blood pressure (BP), lipids, and homeostasis model assessment index of insulin resistance (HOMA-IR) over the course of 2 y in 240 obese (BMI > 97th percentile) children aged 6-14 y (x age: 10.4 y; x BMI: 26.9). Of these 240 children, 203 participated in a 1-y intervention program of physical exercise, nutrition education, and behavior therapy. We compared these children with 37 obese children who underwent no intervention and with 12 normal-weight children of the same age and sex. RESULTS: Obese children had significantly (P < 0.05) higher BP, HOMA-IR, and insulin, triacylglycerol, and LDL-cholesterol concentrations and lower HDL-cholesterol concentrations than did normal-weight children. Twenty-nine children dropped out of the intervention. Only in the 126 children who reduced their SDS-BMI did BP (8% and 12% decreases in systolic and diastolic BP, respectively), lipids (12% and 5% decreases in triacylglycerol and LDL cholesterol, respectively; 7% increase in HDL cholesterol), insulin (13% decrease), and HOMA-IR (17% decrease) improve significantly (P < 0.05). Reduction in SDS-BMI and all benefits regarding CVD risk factors were sustained 1 y after the end of the intervention in the children whose SDS-BMI decreased. CONCLUSIONS: Long-term multidisciplinary intervention led to a reduction in SDS-BMI in most of the obese children 1 y after the end of the intervention. Reduction in SDS-BMI was accompanied by an improvement in CVD risk factors.

Adolescent↗

Conversion from intravenous aminophylline to sustained-release theophylline: computer simulation versus in vivo results.

The accuracy of computer-predicted theophylline serum concentrations compared with actual serum concentrations in patients whose drug therapy was being converted from aminophylline infusions to an oral sustained-release theophylline product (Theo-Dur) was measured. The SIMKIN computer program was used to simulate theophylline serum-concentration curves in nine patients receiving an initial dose of sustained-release theophylline at the time their maintenance aminophylline infusions were discontinued. The sustained-release theophylline doses were calculated using individual patient theophylline clearance values to produce mean theophylline serum concentrations in the normal therapeutic range. Pharmacokinetic variables used in the SIMKIN program were derived from individual patients' serum concentrations and average literature values. Theophylline serum concentrations were measured before the initial dose of the sustained-release product and periodically for 12 hours. Mean SIMKIN-predicted serum theophylline concentrations were within 10% of actual measurements 39% of the time, but data from individual patients varied considerably. Two patients had prolonged absorption lag times that could not be explained. Computer-simulation programs using population-based pharmacokinetic variables to predict theophylline serum concentrations must be tested against in vivo measurements to verify their accuracy.

Adult↗

Long-term impact of the Gatehouse Project on cannabis use of 16-year-olds in Australia.

This study examined the impact of a school-based preventive intervention on cannabis use in adolescence, using a cluster-randomized trial of a multilevel intervention aimed at improving social relationships within schools by promoting change in school environment. Four waves of data were collected at baseline (1997, Year 8: mean age 13 years) and six, 18, and 30 months later (1999, Year 10: mean age 16 years). Self-reported substance use, school engagement, and sociodemographic data were collected using computer-administered questionnaires. Some 2.678(74%) Year 8 students participated (wave 1) with minimal attrition (10% by wave 4). Adjusting for baseline use, weak evidence existed for an intervention effect on the prevalence of any use at Year 10 (OR 0.75, 95% CI 0.54, 1.05) and incident weekly use (OR 0.72, 95% CI 0.39, 1.33). These effects were reduced after adjusting for confounders. Moderate evidence suggested an interaction effect between intervention group and tobacco use (p = 0.04), suggesting the intervention was more effective for non-smokers at baseline (Adj. OR 0.50, 95% CI 0.26, 0.98). This study indicates that a multi-level school-based program may provide an innovative direction for sustainable school interventions with the potential to reduce substance use.

Adolescent↗

Enhanced detection criteria in implantable defibrillators.

INTRODUCTION: Enhanced detection criteria in third-generation implantable defibrillators have been implemented to avoid inappropriate therapy of fast supraventricular arrhythmias. We prospectively analyzed the use of these criteria in patients with an implantable defibrillator with electrogram storing capability. METHODS AND RESULTS: In 82 consecutive patients with a Guidant-CPI implantable defibrillator, sudden onset > 9% and stability < 40 msec were systematically programmed in zone 1 of therapy together with a sustained rate duration security mechanism. All detected tachycardia episodes were analyzed. The study population consisted of 59 patients who had at least one episode of tachycardia detected in zone 1 during follow-up. The tachycardia rate in zone 1 never exceeded 210 beats/min. Twenty patients had no episodes during follow-up, and three patients had episodes detected exclusively in zone 2 of therapy. Supraventricular arrhythmias were detected frequently in the ventricular tachycardia zone (193 of 690 tachycardia episodes in 23 of 59 patients). Use of sudden onset was very effective in detecting sinus tachycardias (65 of 67 episodes), and stability was very useful in detecting atrial fibrillation (31 of 32 episodes). However, sensitivity in detecting ventricular tachycardia was only 90% (451 of 497 episodes). Application of the sustained rate duration criterion allowed appropriate treatment of all ventricular tachycardia episodes, increasing sensitivity to 100%; however, specificity in appropriate nontreatment of supraventricular decreased from 96% to 83%. Subsequent analysis of different algorithms applied to our data showed that sudden onset > 9% and stability < 40 msec was the algorithm with the best specificity and sensitivity. CONCLUSION: Programming sudden onset and stability detection criteria with a sustained rate duration safety net for triggering tachycardia therapy results in appropriate device management in most patients with supraventricular and slow (< 210 beats/min) ventricular tachycardias.

Algorithms↗

Recurrent iodine deficiency in Tasmania, Australia: a salutary lesson in sustainable iodine prophylaxis and its monitoring.

Even mild iodine deficiency during early childhood and pregnancy has the potential to impair neurological development. Often considered a problem of developing nations, a number of industrialized countries are at risk of deficiency. Despite past success with intentional and unintentional iodine fortification, recurrence of deficiency is an ever-present risk. Tasmania, an island state of the Commonwealth of Australia, has a history of endemic iodine deficiency, which was successfully eliminated by iodine prophylaxis initiated in 1950. In this report we describe a formal assessment of iodine nutrition in the Tasmanian population, 50 yr after initiation of the prophylaxis program. The requirements and obstacles to achieving sustainable iodine prophylaxis in an otherwise affluent community are considered. A cross-sectional study was undertaken during the yr 2000. Urinary iodine excretion (UIE) and thyroid ultrasonography were assessed in a representative statewide sample of school-age children. Children (n = 225) aged 4 to 17 yr from throughout Tasmania were studied. The sample comprised 99 girls and 126 boys. The median UIE was 84 microg/liter (87 microg/liter for males and 81 microg/liter for females), with UIE 50 microg/liter or less in 20%. Based on age-specific World Health Organization/International Council for the Control of Iodine Deficiency Disorders normative data for thyroid volume, the prevalence of elevated thyroid volume was 5.3% for boys and 3.5% for girls. However, after correcting the World Health Organization/International Council for the Control of Iodine Deficiency Disorders reference data, the prevalence increased to 24.6% for boys and 20.7% for girls. No significant difference in the thyroid volumes was found between males and females in this study. These data confirm the recurrence of mild iodine deficiency in Tasmania. The failure of sustained iodine prophylaxis highlights the universal importance of persistent surveillance, use of sustainable measures, public awareness, and a specific legislative framework for managing ongoing iodine prophylaxis. Our findings also emphasize the importance of accurate reference data for assessment thyroid volume.

Adolescent↗

[Treatment of malignant ventricular tachyarrhythmia with amiodarone: comparison of empirical administration and administration guided by Holter or ventricular stimulation. Results of the parallel test].

To assess the most appropriate method of administering amiodarone and predicting its efficacy (empiric vs guided by Holter or by ventricular stimulation), 19 patients with sustained ventricular tachycardia or ventricular fibrillation underwent a "parallel study". Fifteen patients were men and 4 women, with a mean age of 65 years. A coronary artery disease with previous myocardial infarction was present in 15 patients, dilated cardiomyopathy in 3 and arrhythmogenic right ventricular dysplasia in 1 (mean left ventricular ejection fraction = 35%). All 19 patients had, as inclusion criteria, 1) frequent (greater than or equal to 30/hour) and/or repetitive (greater than or equal to 10/24 hours) ventricular premature beats during 24-hour Holter monitoring and 2) inducible sustained (greater than 30/sec) ventricular arrhythmias during programmed ventricular stimulation (1-3 extrastimuli from 2 right ventricular sites). Amiodarone was given at an initial dosage of 15 mg/kg/day for 2 weeks and then at a dosage of 5 mg/kg/day. After 15 days 24-hour Holter monitoring and programmed ventricular stimulation were repeated. The data of these tests, however, were not used to guide the therapy that remained empiric, but served only to assess retrospectively the predictive value of Holter monitoring and ventricular stimulation. The following main results were obtained: The mean duration of follow-up was 25 +/- 13 months. During this period 6 patients (32%) died, 3 from sudden and 3 from non-sudden cardiac death. Two other patients had recurrence of sustained ventricular arrhythmias. After 15 days of therapy amiodarone was effective at Holter monitoring in 15 patients (79%) and not effective in 4 (21%). Two of the 15 patients considered responders died suddenly during the follow-up and 2 had arrhythmic recurrence, vs 1 of the 4 non-responder patients who died suddenly (negative predictive value of Holter monitoring: 73%; positive predictive value: 25%; predictive accuracy: 63%). After 15 days of therapy amiodarone was effective at ventricular stimulation in 10 patients (53%) and not effective in 9 (47%). None of the 10 patients considered responders had arrhythmic events during the follow-up, vs 5 of the 9 non-responders, 3 of whom died suddenly and 2 of whom had arrhythmic recurrences (negative predictive value of ventricular stimulation: 100%; positive predictive value: 56%; predictive accuracy: 79%). Only 1 patient discontinued amiodarone after 25 months of follow-up because of development of an important blue-grey skin discoloration.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Significant association of atrial vulnerability with atrial septal abnormalities in young patients with ischemic stroke of unknown cause.

BACKGROUND AND PURPOSE: Atrial septal abnormalities have been associated with cryptogenic ischemic stroke in young patients, but the causal link has not yet been established. Paradoxical embolism is considered the most likely mechanism but is rarely proven. It can be hypothesized that, in those patients, paroxysmal atrial arrhythmias, potentially favored by the anatomic abnormalities, can be another cause of thrombus formation and subsequent embolism to the brain. In this study we assessed the relationship between atrial vulnerability, reflecting arrhythmogenic properties of the atria, and atrial septal abnormalities in young patients with cryptogenic ischemic stroke. METHODS: We enrolled 62 consecutive patients aged <55 years who had ischemic stroke of unknown cause and transesophageal echocardiography to assess atrial septal aneurysm (ASA) or patent foramen ovale (PFO) (ie, atrial septal abnormalities). These patients underwent electrophysiological study to measure atrial refractoriness and conduction time defining a vulnerability index (ie, latent atrial vulnerability) and to assess the inducibility of sustained (lasting >60 seconds) atrial fibrillation with the use of programmed atrial stimulation. Actual atrial vulnerability was defined by the presence of both latent vulnerability and inducibility of sustained atrial fibrillation lasting >60 seconds. RESULTS: We found atrial vulnerability in 58% of patients with atrial septal abnormalities and in 25% of patients without (odds ratio=4.1 [95% CI, 1.3 to 12.7; P<0.02]). The difference between patients with and without PFO or between patients with both PFO and ASA and those without were also significant. Patients with inducible sustained atrial fibrillation had more frequent past history of palpitations and syncope than patients without (P<0.02). CONCLUSIONS: Atrial vulnerability is associated with atrial septal abnormalities in patients with cryptogenic stroke. This result raises the question of the potential role of transient atrial arrhythmias in thrombus formation in the presence of PFO or ASA.

Adult↗

Promising strategies for obesity prevention and treatment within American Indian communities.

In the United States, obesity prevention and treatment programs are dominated by individual-focused strategies. Yet epidemic proportions of obesity and high failure and dropout rates of conventional efforts prompt consideration of alternate approaches. A nonsystematic review of American Indian (AI) health promotion programs highlights a group-focused approach using three primary and two supportive strategies. These strategies are outlined as: (a) build and reinforce social cohesion and collective efficacy, (b) use the motivating force of friendly competition, and (c) aspire to change local norms and policies through assuring high visibility of alternate behaviors and engaging formal and informal leaders. Although evidence to demonstrate the impact of these efforts is limited and not currently available to public health audiences, AI communities' sustained acceptance and continued involvement in the programs suggest that these strategies are worthy of review and consideration by public health practitioners addressing obesity on a national level.

Group Processes↗

Accident prevention program in a glass factory in Shoubra El Khema district.

BACKGROUND: An accident can be defined as an unplanned event that results in or suggests the possibility of personal injury, property damage production interruption diminished health or environmental damage. The accidents have a cost impact on the employees and the company itself. OBJECTIVE: This intervention study was carried out to decrease the accident rate in a glass factory in Shoubra El-Khema district. METHODS: A glass factory in Shoubra El-Khema was selected to implement an intervention program. The program was done through three phases. 1. A preliminary interview questionnaire. 2. Seminars of health education were done to all workers and managers with availability of health education posters, establishment of accident committee and a new reporting system, contract with a housekeeping company was done and also training of some leaders. 3. Concurrent and final evaluation of the program was done. RESULTS: The incidence rate, frequency and severity rate of accidents were decreased at the end of the year after the intervention program. The differences were statistically significant. The opinions of the workers and managers about the different causes of accidents were changed. The belief of the workers and managers about efficiency of health educatio program was changed. Some leaders were trained on skills of health education. Modification of reporting and notification system was done. CONCLUSION: This intervention study succeeded in decreasing accidents rates and increasing the awareness of the managers to decrease accident rates. The beliefs and thoughts o both workers and managers became near to each other. The production loss due to days lost by accidents was reduced. RECOMMENDATIONS: Upgrading process in the factory are recommended to eliminate the hazards at source. Sustaining and continuation of the established preventive program should be done. Trying to apply the program in similar factories is also recommended.

Accidents, Occupational↗

Analysis of the resetting phenomenon in sustained uniform ventricular tachycardia: incidence and relation to termination.

UNLABELLED: Although the phenomenon of resetting has been studied in several experimental and clinical rhythms, it has not been systematically analyzed in ventricular tachycardia. To define the incidence and determinants of resetting as well as its relation to ventricular tachycardia termination, the response to programmed stimulation was prospectively studied during 78 electrically induced episodes of sustained, uniform ventricular tachycardia (mean cycle length 365 +/- 59 ms) in 53 patients. Single and double ventricular extrastimuli were introduced during 78 and 39 episodes of ventricular tachycardia, respectively. Rapid ventricular pacing was performed during 27 episodes. Resetting occurred in response to single ventricular extrastimuli in 43 (55%) of 78 ventricular tachycardias, to double extrastimuli in 31 (79%) of 39 ventricular tachycardias and to rapid pacing in 23 (85%) of 27 ventricular tachycardias. No ventricular tachycardia characteristic distinguished those tachycardias that were reset from those not reset. Termination of ventricular tachycardia occurred in 7 (9%) of 78 episodes with single ventricular extrastimuli, 14 (36%) of 39 episodes with double ventricular extrastimuli and 13 (48%) of 27 episodes with rapid pacing. Termination was less frequent than resetting with both single (9 versus 55%) and double (36 versus 79%) extrastimuli, as well as rapid pacing (48 versus 85%). Resetting preceded termination in 7 of 7 ventricular tachycardias terminated with single ventricular extrastimuli, 12 of 14 terminated with double ventricular extrastimuli and 9 of 13 terminated by rapid pacing. Ventricular tachycardias that were terminated could not be differentiated from those that were reset without termination. IN CONCLUSION: Resetting with programmed extrastimuli is common in hemodynamically stable sustained ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗

The OBRA-87 nursing home regulations and implementation of the Resident Assessment Instrument: effects on process quality.

OBJECTIVE: To characterize changes in key aspects of process quality received by nursing home residents before and after the implementation of the national nursing home Resident Assessment Instrument (RAI) and other aspects of the Omnibus Budget Reconciliation Act (OBRA) nursing home reforms. DESIGN: A quasi-experimental study using a complex, multistage probability-based sample design, with data collected before (1990) and after (1993) implementation of the RAI and other OBRA provisions. SETTING AND PARTICIPANTS: Two independent cohorts (n > 2000) of residents in a random sample of 254 nursing facilities located in metropolitan statistical areas in 10 states. INTERVENTION: OBRA-87 enhanced the regulation of nursing homes and included new requirements on quality of care, resident assessment, care planning, and the use of neuroleptic drugs and physical restraints. One of the key provisions, used to help implement the OBRA requirements in daily nursing home practice, was the mandatory use of a standardized, comprehensive system, known as the RAI, to assist in assessment and care planning. OBRA provisions went into effect in federal law on October 1, 1990, although delays issuing the regulations led to actual implementation of the RAI during the Spring of 1991. MEASUREMENTS AND ANALYSES: Research nurses spent an average of 4 days per facility in each data collection round, assessing a sample of residents, collecting data through interviews with and observations of residents, interviews with multiple shifts of direct staff caregivers for the sampled residents, and review of medical records, including physician's orders, treatment and care plans, nursing progress notes, and medication records. The RNs collected data on the characteristics of the sampled residents, on the care they received, and on facility practices. The effect of being a member of the 1990 pre-OBRA or the 1993 post-OBRA cohort was assessed on the accuracy of information in the residents' medical records, the comprehensiveness of care plans, and on other key aspects of process quality while controlling for any changes in resident case-mix. The data were analyzed using contingency tables and logistic regression and a special statistical software (SUDAAN) to assure proper variance estimation. RESULTS: Overall, the process of care in nursing homes improved in several important areas. The accuracy of information in residents' medical records increased substantially, as did the comprehensiveness of care plans. In addition, several problematic care practices declined during this period, including use of physical restraints (37.4 to 28.1% (P < .001)) and indwelling urinary catheters (9.8 to 7% (P < .001)). There were also increases in good care practices, such as the presence of advanced directives, participation in activities, and use of toileting programs for residents with bowel incontinence. These results were sustained after controlling for differences in the resident characteristics between 1990 and 1993. Other practices, such as use of antipsychotic drugs, behavior management programs, preventive skin care, and provision of therapies were unaffected, or the differences were not statistically significant, after adjusting for changes in resident case-mix. CONCLUSION: The OBRA reforms and introduction of the RAI constituted an unprecedented implementation of comprehensive geriatric assessment in Medicare- and Medicaid-certified nursing homes. The evaluation of the effects of these interventions demonstrates significant improvements in the quality of care provided to residents. At the same time, these findings suggest that more needs to be done to improve process quality. The results suggest the RAI is one tool that facility staff, therapists, pharmacy consultants, and physicians can use to support their continuing efforts to provide high quality of care and life to the nation's 1.7 million nursing home residents.

Advance Directives↗

Electrophysiologic testing in assessment of therapy with sotalol for sustained ventricular tachycardia.

Eighteen patients with sustained ventricular tachycardia underwent electrophysiologic studies to establish the therapeutic efficacy of sotalol. In each patient ventricular tachycardia could be reproducibly initiated by programmed stimulation during control studies. Sotalol prevented induction of sustained ventricular tachycardia in 12 of the 18 patients (67%). Prolongation of the QTC interval and of ventricular refractoriness was regularly observed after sotalol but did not reliably predict prophylactic efficacy. Severe adverse effects, including congestive heart failure and sinus node dysfunction, were noted early during sotalol therapy in three patients. Nine patients were placed on long-term oral treatment with sotalol and four patients on another effective agent. In these 13 patients, complete (12 patients) or partial (one patient) long-term prophylaxis against ventricular tachycardia was documented over a mean follow-up period of 16 months (range 8 to 24). The study suggests that sotalol can provide effective prophylaxis against sustained ventricular tachycardia; this prophylactic efficacy is not typical for pure beta-adrenergic antagonism but may at least partly result from experimentally observed prolongation of the ventricular action potential duration.

Administration, Oral↗

An innovative outcomes-based medical education program built on adult learning principles.

An innovative medical curriculum at the University of New South Wales (UNSW) has been developed through a highly collaborative process aimed at building faculty ownership and ongoing sustainability. The result is a novel capability-based program that features early clinical experience and small-group teaching, which offers students considerable flexibility and achieves a high degree of alignment between graduate outcomes, learning activities and assessments. Graduate capabilities that focus student learning on generic outcomes are described (critical evaluation, reflection, communication and teamwork) along with traditional outcomes in biomedical science, social aspects, clinical performance and ethics. Each two-year phase promotes a distinctive learning process to support and develop autonomous learning across six years. The approaches emphasize important adult education themes: student autonomy; learning from experience; collaborative learning; and adult teacher-learner relationships. Teaching in each phase draws on stages of the human life cycle to provide an explicit organization for the vertical integration of knowledge and skills. A learning environment that values the social nature of learning is fostered through the program's design and assessment system, which supports interdisciplinary integration and rewards students who exhibit self-direction. Assessment incorporates criterion referencing, interdisciplinary examinations, a balance between continuous and barrier assessments, peer feedback and performance assessments of clinical competence. A portfolio examination in each phase, in which students submit evidence of reflection and achievement for each capability, ensures overall alignment.

Australia↗

A framework for monitoring maternal and infant health status.

The Mother and Infant Network (MINET) Program was established in South Western Sydney Area Health Service (SWSAHS) in 1997. MINET developed and implemented an integrated clinical data network as a key strategy to support and inform a Continuum of Care comprising hospital and community based services. There are good data sources within the MINET program. Its scope spans care for mothers and children, which begins with the first antenatal attendance and ends at school entry. This paper has three interrelated aims: to describe the development of the MINET program; to demonstrate the benefits of a sustainable Information Culture which can assist an Area Health Services in adopting a health outcomes based approach to service delivery; and to describe how MINET has the capacity to support Health Services Research.

Female↗

PRDM16 Regulates Prostate Cancer Cell Dormancy and Prevents Bone Metastatic Outgrowth.

UNLABELLED: Understanding dormancy in prostate cancer is challenging because of model availability. In this study, using murine and human prostate cancer cell lines, we generated a stress-induced model of dormancy in vitro and demonstrated that the phenotype could be sustained upon intrailiac artery delivery into the bone marrow microenvironment. RNA sequencing analysis revealed that the transcription factor positive regulatory domain-containing 16 (PRDM16) was commonly upregulated in dormant prostate cancer cells compared with controls. Furthermore, bone marrow-disseminated prostate cancer cells from primary orthotopic tumors were largely positive for PRDM16. Genetic ablation and forced ectopic expression supported a role for PRDM16 in maintaining prostate cancer dormancy in vitro and in vivo. Clinically, PRDM16 negatively correlated with disease recurrence and with the E2F cell-cycle program in disseminated tumor cells derived from the bone marrow of patients with prostate cancer. Gene enrichment and characterization studies implicated PRDM16 as a regulator of metabolic and cell-cycle pathways. Chromatin immunoprecipitation-qPCR further revealed that PRDM16 binds upstream of the promoter of RB1, a potent repressor of E2F activity. Overall, this study developed a straightforward method for inducing cancer cell dormancy and applied this approach to find that PRDM16 governs an intrinsic dormancy program in prostate cancer. SIGNIFICANCE: PRDM16 initiates a dormancy program in prostate cancer cells that is sustained in the bone marrow microenvironment, highlighting PRDM16 as a potential biomarker for relapse and target for eliminating dormant cancer cells.

Male↗