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.

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.

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.

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.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis presenting as confusion, dysphasia, and myoclonus.

Steroid response encephalopathy associated with autoimmune thyroiditis (SREAT), or Hashimoto's encephalopathy, is a rare disorder believed to be immune-mediated. It is most often characterized by a subacute onset of confusion with altered level of consciousness, seizures, and myoclonus. We describe the case of a 48-year-old gentleman who presented with confusion and dysphasia. Specific clinical features and laboratory results led to a diagnosis of Hashimoto's encephalopathy. This case highlights the core features of this condition and the potential for complete response to steroid therapy.

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.

Reversible Foix-Chavany-Marie Syndrome in a patient treated for hydrocephalus.

The authors report the first known case of Foix-Chavany-Marie Syndrome in a patient with hydrocephalus that reversed with ventriculoperitoneal shunting. A 34-year-old x-ray technician with a history of pilocytic astrocytoma resection and radiotherapy and ventriculoperitoneal shunt placement as a child presented with altered mental status and nausea. She was found to have acute hydrocephalus. Post-operatively she did well and was discharged home. The next day she became acutely altered with anarthria, difficulty speaking, and stiff facial muscles. After multiple revisions, she slowly recovered to her pre-op baseline over the course of next 2 months. This is the first known case of acute hydrocephalus causing Foix-Chavany-Marie Syndrome. Additionally, we show that this unique syndrome is slowly reversible after treatment of hydrocephalus.

Spontaneous intracranial hypotension.

INTRODUCTION: Spontaneous/primary intracranial hypotension is characterised by orthostatic headache and is associated with characteristic magnetic resonance imaging findings. CASE REPORT: We present a case report of a patient with typical symptoms and classical radiological images. DISCUSSION: Spontaneous intracranial hypotension is an under-recognised cause of headache and can be diagnosed by history of typical orthostatic headache and findings on MRI brain.

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.

Multiple sclerosis exceptionally presenting as parkinsonism responds to intravenous methylprednisolone.

Parkinsonism due to multiple sclerosis (MS) is rare. In previously reported patients with MS-induced parkinsonism, MS manifested first, followed a typical clinical course, and parkinsonism developed later in the course of the illness. We report a 52-year-old male presenting with parkinsonism as the initial manifestation of MS, in whom a subsequent MS relapse consisted of marked deterioration in parkinsonism, a clinical pattern not previously described in MS. A brain MRI demonstrated involvement of the substantia nigra and basal ganglia. This patient illustrates that the clinical presentation and progression of MS may rarely be characterised by predominating parkinsonian features which are reversible by treatment with intravenous methylprednisolone and interferon beta1a.

A rare cause of fatal intracranial haemorrhage.

INTRODUCTION: We report the case of a 53-year-old farmer with a 5-day history of severe headache, photophobia and neck stiffness. Full blood count (platelets 173), coagulation screen were normal throughout. Liver function tests remained normal apart from an elevated gamma-GT (156). CT Brain was normal. CSF analysis showed a WCC of 454/mm(3) (60% lymphocytes), elevated CSF protein (1.42 g/l) and a normal CSF glucose. He was commenced on IV antibiotics and IV acyclivor and improved. On day 3 of admission, he complained of a sudden severe headache, became unresponsive (GCS 3/15). INVESTIGATIONS: CT Brain showed a massive left intraventricular haemorrhage. He died 4 days later. Subsequent serum serology for leptospirosis was positive. A repeat sample taken 4 days post-admission, showed a rising IgM indicating active leptospirosis. Detailed pathological examination confirmed intracerebral haemorrhage with normal cerebral vasculature. CONCLUSION: Leptospirosis is a rare cause of intracerebral haemorrhage even in the absence of coagulopathy.

Arabidopsis AtCNGC10 rescues potassium channel mutants of E. coli, yeast and Arabidopsis and is regulated by calcium/calmodulin and cyclic GMP in E. coli.

We have isolated and characterised AtCNGC10, one of the 20 members of the family of cyclic nucleotide (CN)-gated and calmodulin (CaM)-regulated channels (CNGCs) from Arabidopsis thaliana (L.) Heynh. AtCNGC10 bound CaM in a C-terminal subregion that contains a basic amphiphillic structure characteristic of CaM-binding proteins and that also overlaps with the predicted CN-binding domain. AtCNGC10 is insensitive to the broad-range K+ channel blocker, tetraethylammonium, and lacks a typical K+-signature motif. However, AtCNGC10 complemented K+ channel uptake mutants of Escherichia coli (LB650), yeast (Saccharomyces cerevisiae CY162) and Arabidopsis (akt1-1). Sense 35S-AtCNGC10 transformed into the Arabidopsis akt1-1 mutant, grew 1.7-fold better on K+-limited medium relative to the vector control. Coexpression of CaM and AtCNGC10 in E. coli showed that Ca2+ / CaM inhibited cell growth by 40%, while cGMP reversed the inhibition by Ca2+ / CaM, in a AtCNGC10-dependent manner. AtCNGC10 did not confer tolerance to Cs+ in E. coli, however, it confers tolerance to toxic levels of Na+ and Cs+ in the yeast K+ uptake mutant grown on low K+ medium. Antisense AtCNGC10 plants had 50% less potassium than wild type Columbia. Taken together, the studies from three evolutionarily diverse species demonstrated a role for the CaM-binding channel, AtCNGC10, in mediating the uptake of K+ in plants.

Concurrent hereditary haemochromatosis and idiopathic Parkinson's disease: a case report series.

Hereditary haemochromatosis (HH) is a genetic disorder in which abnormal iron handling leads to excessive iron accumulation in systemic tissues. Magnetic resonance imaging studies suggest excess iron deposition in the basal ganglia of patients with HH. The symptoms of neurological complications of HH include cognitive decline, gait difficulties, cerebellar ataxia, and extrapyramidal dysfunction, but idiopathic Parkinson's disease, in which brain iron deposition is normal, has not been reported. We describe four patients with concurrent HH and IPD. Although three of the cases had risk factors for cerebrovascular and cardiovascular disease, computed tomography did not show ischaemic changes in the basal ganglia. We speculate that in these cases, abnormal deposition of iron in the basal ganglia induced the symptoms of IPD.

Persistence and perceived consequences of cannabis use and dependence among young adults: implications for policy.

AIMS: To document patterns of cannabis use and dependence from late-adolescence through to the mid-twenties; to describe perceived consequences of cannabis use among young people; and to consider policy implications of these findings. METHODS: This was a longitudinal study of the Dunedin Multidisciplinary Health and Development Study birth cohort with repeated measures of cannabis use at ages 18, 21 and 26 years. RESULTS: Twelve month prevalence rates of cannabis use (just over 50%) and dependence (just under 10%) remained stable between age 21 and 26 years, contrary to an expected decline. Cannabis dependence, as distinct from occasional use, was associated with high rates of harder drug use, selling of drugs and drug conviction. Cumulatively, almost 3/4 of our cohort had tried cannabis by age 26. Young people thought the risk of getting caught using cannabis was trivial, and that using cannabis had few negative social consequences. CONCLUSIONS: The persistent high rates of cannabis use and dependence among young New Zealand adults raises important issues for policy makers. Current laws are not particularly effective in deterring use. Whereas occasional use does not appear to present a serious problem, cannabis dependence among users is a serious public health issue that warrants immediate action.