First Observation of Cyclotron Radiation from MeV-Scale e

We present an apparatus for detection of cyclotron radiation yielding a frequency-based ß^{±} kinetic energy determination in the 5 keV to 2.1 MeV range, characteristic of nuclear ß decays. The cyclotron frequency of the radiating ß particles in a magnetic field is used to determine the ß energy precisely. Our work establishes the foundation to apply the cyclotron radiation emission spectroscopy (CRES) technique, developed by the Project 8 Collaboration, far beyond the 18-keV tritium endpoint region. We report initial measurements of ß^{-}'s from ^{6}He and ß^{+}'s from ^{19}Ne decays to demonstrate the broadband response of our detection system and assess potential systematic uncertainties for ß spectroscopy over the full (MeV) energy range. To our knowledge, this is the first direct observation of cyclotron radiation from individual highly relativistic ß's in a waveguide. This work establishes the application of CRES to a variety of nuclei, opening its reach to searches for new physics beyond the TeV scale via precision ß-decay measurements.

Which adolescents develop persistent substance dependence in adulthood? Using population-representative longitudinal data to inform universal risk assessment.

BACKGROUND: To our knowledge, there are no universal screening tools for substance dependence that (1) were developed using a population-based sample, (2) estimate total risk briefly and inexpensively by incorporating a relatively small number of well-established risk factors, and (3) aggregate risk factors using a simple algorithm. We created a universal screening tool that incorporates these features to identify adolescents at risk for persistent substance dependence in adulthood. METHOD: Participants were members of a representative cohort of 1037 individuals born in Dunedin, New Zealand in 1972-1973 and followed prospectively to age 38 years, with 95% retention. We assessed a small set of childhood and adolescent risk factors: family history of substance dependence, childhood psychopathology (conduct disorder, depression), early exposure to substances, frequent substance use in adolescence, sex, and childhood socioeconomic status. We defined the outcome (persistent substance dependence in adulthood) as dependence on one or more of alcohol, tobacco, cannabis, or hard drugs at ⩾3 assessment ages: 21, 26, 32, and 38 years. RESULTS: A cumulative risk index, a simple sum of nine childhood and adolescent risk factors, predicted persistent substance dependence in adulthood with considerable accuracy (AUC = 0.80). CONCLUSIONS: A cumulative risk score can accurately predict which adolescents in the general population will develop persistent substance dependence in adulthood.

Internalizing disorders and leukocyte telomere erosion: a prospective study of depression, generalized anxiety disorder and post-traumatic stress disorder.

There is evidence that persistent psychiatric disorders lead to age-related disease and premature mortality. Telomere length has emerged as a promising biomarker in studies that test the hypothesis that internalizing psychiatric disorders are associated with accumulating cellular damage. We tested the association between the persistence of internalizing disorders (depression, generalized anxiety disorder and post-traumatic stress disorder) and leukocyte telomere length (LTL) in the prospective longitudinal Dunedin Study (n=1037). Analyses showed that the persistence of internalizing disorders across repeated assessments from ages 11 to 38 years predicted shorter LTL at age 38 years in a dose-response manner, specifically in men (ß=-0.137, 95% confidence interval (CI): -0.232, -0.042, P=0.005). This association was not accounted for by alternative explanatory factors, including childhood maltreatment, tobacco smoking, substance dependence, psychiatric medication use, poor physical health or low socioeconomic status. Additional analyses using DNA from blood collected at two time points (ages 26 and 38 years) showed that LTL erosion was accelerated among men who were diagnosed with internalizing disorder in the interim (ß=-0.111, 95% CI: -0.184, -0.037, P=0.003). No significant associations were found among women in any analysis, highlighting potential sex differences in internalizing-related telomere biology. These findings point to a potential mechanism linking internalizing disorders to accelerated biological aging in the first half of the life course, particularly in men. Because internalizing disorders are treatable, the findings suggest the hypothesis that treating psychiatric disorders in the first half of the life course may reduce the population burden of age-related disease and extend health expectancy.

Specificity of childhood psychotic symptoms for predicting schizophrenia by 38 years of age: a birth cohort study.

BACKGROUND: Childhood psychotic symptoms have been used as a subclinical phenotype of schizophrenia in etiological research and as a target for preventative interventions. However, recent studies have cast doubt on the specificity of these symptoms for schizophrenia, suggesting alternative outcomes such as anxiety and depression. Using a prospective longitudinal birth cohort we investigated whether childhood psychotic symptoms predicted a diagnosis of schizophrenia or other psychiatric disorders by 38 years of age. METHOD: Participants were drawn from a birth cohort of 1037 children from Dunedin, New Zealand, who were followed prospectively to 38 years of age (96% retention rate). Structured clinical interviews were administered at age 11 to assess psychotic symptoms and study members underwent psychiatric assessments at ages 18, 21, 26, 32 and 38 to obtain past-year DSM-III-R/IV diagnoses and self-reports of attempted suicides since adolescence. RESULTS: Psychotic symptoms at age 11 predicted elevated rates of research diagnoses of schizophrenia and posttraumatic stress disorder (PTSD) and also suicide attempts by age 38, even when controlling for gender, social class and childhood psychopathology. No significant associations were found for persistent anxiety, persistent depression, mania or persistent substance dependence. Very few of the children presenting with age-11 psychotic symptoms were free from disorder by age 38. CONCLUSIONS: Childhood psychotic symptoms were not specific to a diagnosis of schizophrenia in adulthood and thus future studies of early symptoms should be cautious in extrapolating findings only to this clinical disorder. However, these symptoms may be useful as a marker of adult mental health problems more broadly.

Zigzag persistence for coral reef resilience using a stochastic spatial model.

A complex interplay between species governs the evolution of spatial patterns in ecology. An open problem in the biological sciences is characterizing spatio-temporal data and understanding how changes at the local scale affect global dynamics/behaviour. Here, we extend a well-studied temporal mathematical model of coral reef dynamics to include stochastic and spatial interactions and generate data to study different ecological scenarios. We present descriptors to characterize patterns in heterogeneous spatio-temporal data surpassing spatially averaged measures. We apply these descriptors to simulated coral data and demonstrate the utility of two topological data analysis techniques-persistent homology and zigzag persistence-for characterizing mechanisms of reef resilience. We show that the introduction of local competition between species leads to the appearance of coral clusters in the reef. We use our analyses to distinguish temporal dynamics stemming from different initial configurations of coral, showing that the neighbourhood composition of coral sites determines their long-term survival. Using zigzag persistence, we determine which spatial configurations protect coral from extinction in different environments. Finally, we apply this toolkit of multi-scale methods to empirical coral reef data, which distinguish spatio-temporal reef dynamics in different locations, and demonstrate the applicability to a range of datasets.

Progressive multifocal leucoencephalopathy in a patient with idiopathic CD4+ lymphocytopenia.

Progressive multifocal leucoencephalopathy (PML) is an opportunistic, demyelinating neurological disease caused by reactivation of the JC polyomavirus. PML occurs almost exclusively in immunosuppressed individuals, with only isolated case reports of PML occurring in patients without apparent immunosuppression. Idiopathic CD4+ lymohocytopenia (ICL) is a syndrome defined by the Centre for Disease Control and Prevention as a CD4+ count <300 cells/uL or <20% of total T cell count on >1 occasion, with no evidence of human immunodeficiency virus (HIV) infection, and the absence of other known immunodeficiency or therapy associated with lymphocytopenia. We describe a case of PML occurring in a patient with idiopathic CD4+ lymphocytopenia.

Research capacity training for surveillance and response in the Indo-Pacific: a case study of implementation.

SETTING: Surveillance and response workforce in the Indo-Pacific region, including Papua New Guinea (PNG), Solomon Islands, Fiji, Eastern Indonesia and Timor-Leste. OBJECTIVE: To evaluate the implementation of a modified WHO SORT IT research training programme which included a workplace-based research project. The training was designed for surveillance and response frontline workforce in the Indo-Pacific region. DESIGN: This was a programme evaluation using mixed methods. Fifty-three health and biosecurity workers from Fiji, Indonesia, PNG, Solomon Islands and Timor-Leste participated in the research training programme. RESULTS: Implementation of the programme was modified to reflect the context of participant countries. Work-place research projects focused on priority issues identified by local policy makers and in-country stakeholders. Self-reported research skills showed a significant increase (P < 0.01) after the completion of training. Participants reported high scores for satisfaction with training. CONCLUSIONS: This case study provides lessons learnt for future research training, and demonstrates that the SORT IT model can be modified to reflect the context of implementation without compromising purpose or outcomes.

CONTEXTE: Personnel de surveillance et d'intervention dans la région Indo-Pacifique incluant la Papouasie-Nouvelle-Guinée (PNG), les îles Salomon, les Fiji, l'Est de l'Indonesia et Timor-Leste. OBJECTIF: Évaluer la mise en œuvre d'un programme de formation modifiée WHO SORT-IT incluant un projet de recherche sur les lieux de travail. La formation était conçue pour le personnel de surveillance et d'intervention de première ligne dans la région Indo-Pacifique. SCHÉMA: Evaluation de programme utilisant des méthodes mixtes. Cinquante-trois travailleurs en matière de santé et de biosécurité venant des Fiji, d'Indonesie, de PNG, des îles Salomon et du Timor-Leste ont participé au programme de formation à la recherche. RÉSULTATS: La mise en œuvre du programme a été modifiée pour refléter le contexte des pays participants. Les projets de recherche sur les lieux de travail se sont focalisés sur les problèmes prioritaires identifiés par les responsables de la politique locale et les parties prenantes du pays. Les capacités de recherche rapportées par les participants ont montré une augmentation significative (P < 0,01) après la fin de la formation. Les participants ont exprimé de hauts scores de satisfaction à propos de la formation. CONCLUSION: Cette étude de cas fournit des leçons pour les formations en recherche à venir et démontré que le modèle SORT IT pouvait être modifié pour refléter le contexte de sa mise en œuvre sans compromettre le but ni les résultats.

Heat shock modulates phosphorylation status and activity of nucleoside diphosphate kinase in cultured sugarcane cells.

Nucleoside diphosphate kinase (NDPK) is involved in the regeneration of nucleoside triphosphates (NTPs) through its phosphotransferase activity via an autophosphorylating histidine residue. Additionally, autophosphorylation of serine and/or threonine residues is documented for NDPKs from various organisms. However, the metabolic significance of serine/threonine phosphorylation has not been well characterized. In this study we report the cloning and characterization of NDPKI from cultured sugarcane (Saccharum officinarum L. line H50-7209) cells, and modulation of serine autophosphorylation of NDPK1 in response to heat-shock (HS). Heat-shock treatment at 40°C for 2 h resulted in a 40% reduction in labeled phosphoserine in NDPK1. This dephosphorylation was accompanied by an increase in NDPK enzyme activity. In contrast, NDPK1 in cultured tobacco (cv. W-38) cells did not show changes in autophosphorylation or increased enzyme activity in response to HS. The mRNA or protein level of NDPK1 did not increase in response to HS. Sugarcane cells sustain the constitutive protein synthesis in addition to heat-shock protein synthesis during HS, while constitutive protein synthesis is significantly reduced in tobacco cells during HS. Thus, HS modulation of NDPK1 activity and serine dephosphorylation in sugarcane cells may represent an important physiological role in maintaining cellular metabolic functions during heat stress.

Children's self-reported psychotic symptoms and adult schizophreniform disorder: a 15-year longitudinal study.

BACKGROUND: Childhood risk factors for the development of adult schizophrenia have proved to have only modest and nonspecific effects, and most seem unrelated to the adult phenotype. We report the first direct examination of the longitudinal relationship between psychotic symptoms in childhood and adulthood. METHODS: We analyzed prospective data from a birth cohort (N = 761), in which children were asked about delusional beliefs and hallucinatory experiences at age 11 years, and then followed up to age 26 years. Structured diagnostic interviews were employed at both ages and self-report of schizophreniform symptoms was augmented by other data sources at age 26 years. RESULTS: Self-reported psychotic symptoms at age 11 years predicted a very high risk of a schizophreniform diagnosis at age 26 years (odds ratio, 16.4; 95% confidence interval, 3.9-67.8). In terms of attributable risk, 42% of the age-26 schizophreniform cases in the cohort had reported 1 or more psychotic symptoms at age 11 years. Age-11 psychotic symptoms did not predict mania or depression at age 26 years, suggesting specificity of prediction to schizophreniform disorder. The link between child and adult psychotic symptoms was not simply the result of general childhood psychopathology. CONCLUSION: These findings provide the first evidence for continuity of psychotic symptoms from childhood to adulthood.

Randomized controlled study of a retiree health promotion program. The Bank of American Study.

The initial results of a 12-month controlled trial of a health promotion program in 5686 Bank of America retirees, randomized into full program, questionnaire only, and insurance claims only groups, were analyzed to determine whether the health promotion program was effective. Comparisons were between program and questionnaire only groups for self-reported health habit changes, health risk scores, medical care utilization, and days confined to home, and between all groups for insurance claims data. The intervention, or full program, included health habit questionnaires administered every 6 months, individualized time-oriented health risk appraisals, personal recommendation letters, self-management materials, and a health promotion book. Twelve-month changes in health habits, health status, and economic variables favored the full program group in 31 of 32 comparisons and were statistically significant at the .05 level in two-tailed tests in 19 comparisons and at the .01 level in two-tailed tests in 13 comparisons. Over 12 months, overall computed health risk scores decreased by 4.3% in the full program experimental group and increased by 7.2% in the questionnaire only control group. Total direct and indirect costs decreased by 11% in the experimental group and increased by 6.3% in the questionnaire only control group. Analysis of claims data confirmed these trends. A low-cost health promotion program for retirees was effective in changing health behaviors and has potential to decrease health care utilization.

Carotid body tumor associated with partial Horner's syndrome and facial pain ('Raeder's syndrome').

A 35-year-old woman had partial, right-sided Horner's syndrome seven years prior to admission. Facial sweating was normal. Ipsilateral headache and facial pain followed a year later. Three months before admission a left-sided carotid body tumor was resected successfully. Soon thereafter, a mass was noted below the right mandibular angle and carotid angiography showed features typical of a carotid body tumor at the carotid bifurcation. To our knowledge this is the first report of such a lesion causing Raeder's syndrome. Review of other reported cases of this usually benign syndrome shows that some may be associated with serious but treatable diseases of the internal carotid artery.

Abnormalities of multimodality evoked potentials in amyotrophic lateral sclerosis.

Thirty-two patients with amyotrophic lateral sclerosis were studied with somatosensory evoked potentials (SEPs), visual evoked potentials, and brain-stem auditory evoked potentials. H-reflexes were used to screen for abnormalities of peripheral nerve conduction. Nineteen patients (59%) showed an abnormality of lower extremity SEPs. In 13 patients (40%) the delay was of central origin, while in six patients (19%) peripheral conduction delay was possible. Abnormality of upper limb SEPs was seen in 11 patients (34%), all but two of whom had abnormal lower limb SEPs as well. Four patients (12%) had abnormal brain-stem auditory evoked potentials, all of whom had abnormal SEPs from upper and lower limbs. Four patients had abnormal visual evoked potentials, which in three patients were of minor degree. These results give physiologic evidence to suggest that abnormalities in amyotrophic lateral sclerosis occur outside the motor system.

Intracerebral hemorrhage and oral amphetamine.

Four patients suffered intracerebral hemorrhages following the oral or nasal use of amphetamine or related compounds. Two of these patients had abnormal-appearing cerebral blood vessels on angiography. Review of previously reported cases showed that intracerebral hemorrhage may occur in patients using the drug for the first time and for nonrecreational purposes.

Failure of immunosuppression with a ten- to 14-day course of high-dose intravenous cyclophosphamide to alter the progression of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive disorder of the nervous system for which there is no known treatment. Because recent studies have suggested that there may be abnormalities of the immune function in patients with ALS and since we have found a beneficial effect from a short course of intensive immunosuppression with cyclophosphamide in progressive multiple sclerosis, we treated six patients with ALS with a ten- to 14-day course of intensive immunosuppression in a pilot study. At 18 months following therapy, all patients showed a continued progression of the disease; four of the six patients died. We conclude that this form of immunosuppression does not alter the course of ALS.

Ganglioside therapy for amyotrophic lateral sclerosis: a double-blind controlled trial.

A 6-month double-blind study of bovine brain gangliosides was carried out in 40 patients with ALS. Thirty-two patients completed the study; 18 were treated with gangliosides and 14 with placebo. Using 10 different objective tests of muscle strength, we failed to show a significant difference between the two groups in the progression of weakness. Daily intramuscular injections of 40 mg of brain gangliosides for 6 months had no beneficial effect in ALS.

Surgical treatment of post-lumbar puncture dural CSF leak causing chronic headache. Case report.

A 58-year-old woman experienced incapacitating headache and occipital paresthesiae for 5 years after lumbar myelography. Conservative methods of treatment failed. Successive investigations for a suspected cerebrospinal fluid (CSF) leak were unrevealing. Leakage of CSF from the subarachnoid space into the epidural space in the lumbar region was finally confirmed when oil-soluble contrast material (Pantopaque), injected into the cervical subarachnoid space, was revealed by a specific technical modification to be escaping from the lumbar sac. Repair of the dural defect with dorsolumbar fascia resulted in almost complete alleviation of symptoms. This case is unusual because of the radiographic technique used, the duration of symptoms, and the rarity of reports of successful surgical treatment for this serious complication of lumbar puncture.

Personality differences predict health-risk behaviors in young adulthood: evidence from a longitudinal study.

In a longitudinal study of a birth cohort, the authors identified youth involved in each of 4 different health-risk behaviors at age 21: alcohol dependence, violent crime, unsafe sex, and dangerous driving habits. At age 18, the Multidimensional Personality Questionnaire (MPQ) was used to assess 10 distinct personality traits. At age 3, observational measures were used to classify children into distinct temperament groups. Results showed that a similar constellation of adolescent personality traits, with developmental origins in childhood, is linked to different health-risk behaviors at 21. Associations between the same personality traits and different health-risk behaviors were not an artifact of the same people engaging in different health-risk behaviors; rather, these associations implicated the same personality type in different but related behaviors. In planning campaigns, health professionals may need to design programs that appeal to the unique psychological makeup of persons most at risk for health-risk behaviors.

Health risk changes with a low-cost individualized health promotion program: effects at up to 30 months.

BACKGROUND AND PURPOSE: Health promotion programs are increasingly important components of health care in an era of predominantly chronic illness preceded by identified health risk behaviors. We report a large and relatively long experience with a low-cost intervention delivered through the mail and using sequential time-oriented risk appraisal and personalized recommendations, each six months, together with self-management materials. METHODS: We performed a prospective, longitudinal, observational study of 103,937 consecutive program participants observed for at least six months and up to 30 months. The primary study endpoint is overall health risk score, with secondary analysis of individual risk behaviors. A concurrent comparison group utilizes the initial scores of new participants by calendar time over the study period. RESULTS: Strong overall positive effects were observed, with improvement in computed health risk scores over 18 months of 14.7% (p less than .0001) in those 65 and over and 18.4% (p<.0001) in those under 65. At 30 months, improvement was 18.8% (p less than .0001) and 25.7% (p less than .0001), respectively. There was improvement in self-report scores for all targeted health risk behaviors, except for pounds over ideal weight, including smoking; dietary fat, salt, and fiber; alcohol; exercise; cholesterol; and reported stress. There was progressive improvement approximating 5% each six-month period. Results were consistent across age groups 16-35, 36-50, 51-65, and over 65 and over different educational level. Results could not be accounted for by sequential changes in initial health habits of participants over time. DISCUSSION: (ABSTRACT TRUNCATED AT 250 WORDS)

Randomized controlled trial of cost reductions from a health education program: the California Public Employees' Retirement System (PERS) study.

Purpose. This study evaluated the cost trend reduction from a health promotion program. Design. A randomized 12-month trial comparing claims data was conducted. Additional studies, utilizing quasi-experimental designs, analyzed changes in health habits and changes in costs estimated by self-report. Subjects. All active California Public Employees' Retirement System (PERS) employees (21,170), non-Medicare eligible retirees (8,316), and retirees with Medical Supplement coverage (25,416) administered by Blue Shield of California were included. Intervention. The program consisted of mailed health risk assessments at six- or 12-month intervals, with individualized reports and recommendation letters sent to participants emphasizing and encouraging change, self-management materials emphasizing self-care when appropriate, and quarterly newsletters. Passive participants received printed materials only. Measures. Health risks were based upon self-report; summary scores were computed by modified Framingham algorithms. Self-report cost data were estimated from reported doctor visits, hospital days, and days sick or confined to home. Claims data were those paid by Blue Shield of California. Results. The program was associated with: 1) reduction in health risk scores at 12 months, (p less than .001), 2) reduction of subject reported medical utilization from baseline (p less than .05), and 3) decrease in claims cost growth relative to controls (p=.03). Annual claims costs were approximately $3.2 to $8.0 million less than expected had costs for the experimental participants increased at the same rate as the control group. Discussion. Results suggest that appropriately designed health promotion programs can reduce health risks and at the same time reduce the medical care claims cost trend.