Investigating the transmission risk of infectious disease outbreaks through the Aotearoa Co-incidence Network (ACN): a population-based study.

BACKGROUND: The emergence and re-emergence of infectious diseases presents a significant challenge to public health and broader society. This study utilises novel nationwide data to calculate the transmission risk and potential inequity of infectious disease outbreaks through use of network analysis. METHODS: Nationwide employment and education microdata (∼4.7 million individuals in Aotearoa New Zealand) were used to develop the Aotearoa Co-incidence Network (ACN). The ACN considers connections generated when individuals are employed at the same workplaces or enrolled at the same schools. Through forms of network analysis, connections between geospatial areas can be established and provide proxy measures of infectious disease transmission risk. The ACN was also overlayed with nationwide population vulnerability data based on the number of older adults (>65 years) and individuals with long-term health conditions. FINDINGS: We identify areas that have both high potential transmission risk (i.e., highly connected) and high vulnerability to infectious diseases. Community detection identified geographic boundaries that can be relevant to the application of regional restrictions for limiting infectious disease transmission. INTERPRETATION: Integrating novel network science and geospatial analytics provides a simple way to study infectious disease transmission risk and population vulnerability to outbreaks. Our replicable method has utility for researchers globally with access to such data. It can help inform equitable preparation for, and responses to infectious disease outbreaks. FUNDING: This project was funded by the Health Research Council of New Zealand (20/1442) and from the NZ Government via Ministry for Business Innovation and Employment and Department of Prime Minister and Cabinet.

An overview of systematic reviews on the public health consequences of social isolation and loneliness.

OBJECTIVES: Social isolation and loneliness have been associated with ill health and are common in the developed world. A clear understanding of their implications for morbidity and mortality is needed to gauge the extent of the associated public health challenge and the potential benefit of intervention. STUDY DESIGN: A systematic review of systematic reviews (systematic overview) was undertaken to determine the wider consequences of social isolation and loneliness, identify any differences between the two, determine differences from findings of non-systematic reviews and to clarify the direction of causality. METHODS: Eight databases were searched from 1950 to 2016 for English language reviews covering social isolation and loneliness but not solely social support. Suitability for inclusion was determined by two or more reviewers, the methodological quality of included systematic reviews assessed using the a measurement tool to assess systematic reviews (AMSTAR) checklist and the quality of evidence within these reviews using the grading of recommendations, assessment, development and evaluations (GRADE) approach. Non-systematic reviews were sought for a comparison of findings but not included in the primary narrative synthesis. RESULTS: Forty systematic reviews of mainly observational studies were identified, largely from the developed world. Meta-analyses have identified a significant association between social isolation and loneliness with increased all-cause mortality and social isolation with cardiovascular disease. Narrative systematic reviews suggest associations with poorer mental health outcomes, with less strong evidence for behavioural and other physical health outcomes. No reviews were identified for wider socio-economic or developmental outcomes. CONCLUSIONS: This systematic overview highlights that there is consistent evidence linking social isolation and loneliness to worse cardiovascular and mental health outcomes. The role of social isolation and loneliness in other conditions and their socio-economic consequences is less clear. More research is needed on associations with cancer, health behaviours, and the impact across the life course and wider socio-economic consequences. Policy makers and health and local government commissioners should consider social isolation and loneliness as important upstream factors impacting on morbidity and mortality due to their effects on cardiovascular and mental health. Prevention strategies should therefore be developed across the public and voluntary sectors, using an asset-based approach.

Estilos sanos de vida en adultos con discapacidad intelectual: qué conocen, factores que los benefician y dificultan / No disponible

Las personas con discapacidad intelectual son más propensas a tener problemas de salud que las que no la tienen. Hasta ahora se ha investigado poco la salud desde la perspectiva de las propias personas con discapacidad intelectual. Intentamos centrarnos sobre qué es lo que estas personas entienden por estar sanos, y cuáles son sus experiencias sobre los estilos sanos de vida. Se llevaron a cabo entrevistas semiestructuradas a 13 adultos con discapacidad intelectual para preguntarles sobre su salud y estilos sanos de vida. Los datos fueron analizados por los temas recogidos. Los participantes demostraron comprender el significado de estar sanos, llevar una dieta sana, los peligros del uso de sustancias y los beneficios del ejercicio. Mostraron cierto conocimiento sobre las razones para embarcarse en conductas sanas. Surgió la idea de la moderación, así como la existencia de factores que benefician y dificultan la implicación en un estilo sano de vida. Estos resultados sugieren que las personas con discapacidad intelectual demuestran tener cierta comprensión de lo que constituye estar sano y ser conscientes de los estilos sanos de vida, las consecuencias de conductas poco sanas y la necesidad de tener moderación (AU)

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Simple measurement of aneurysm residual after treatment: the SMART scale for evaluation of intracranial aneurysms treated with flow diverters.

BACKGROUND: Primary endovascular reconstruction with flow diversion represents a fundamental paradigm shift in the technique of endovascular aneurysm treatment. Unlike coil embolization, often there remains residual post-procedural filling within the aneurysm with flow diverters, the curative reconstruction presumably occurring over a period of weeks. Thus, conventional grading scales for post-procedural aneurysm occlusion and recanalization are inadequate. The aim of this paper is to propose a new angiographic grading scale that addresses this fundamentally new treatment option. METHOD: A five-point grading scale describes the location of residual flow within the aneurysm in the venous phase [grade 1: patent aneurysm with diffuse inflow; grade 2: residual filling of the aneurysm dome (saccular) or wall (fusiform); grade 3: only residual neck (saccular) or only intra-aneurysmal filling with former boundaries covered (fusiform); grade 4: complete occlusion]. FINDINGS: Grade 0 represents any aneurysm, regardless of occlusion rate with early phase, coherent inflow jet. Intra-aneurysmal flow stagnation is categorized into: (a) none, (b) capillary phase, and (c) venous phase. Prevailing parent vessel hemodynamics with in-stent stenosis (ISS) are divided into none (ISS0), mild (ISS1), moderate (ISS2), severe (ISS3), and total (ISS4) occlusion. The proposed grading scales allow assessment of the hemodynamic consequences of stent placement on endosaccular in-flow, stasis, and location of stasis as well as parent vessel hemodynamics. CONCLUSIONS: Further studies need to show the applicability and possible predictive value of this new grading scale on the efficacy of the stent in promoting intra-aneurysmal flow stagnation, thus creating the potential to harmonize the results of future papers. This may help to optimize treatment and future device design.

The production of hydrogen peroxide during early-stage protein aggregation: a common pathological mechanism in different neurodegenerative diseases?

By means of an ESR spin-trapping method, we have shown that Abeta (amyloid beta), alpha-synuclein and various toxic forms of the prion protein all appear to generate H2O2 in vitro. A fundamental molecular mechanism underlying the pathogenesis of cell death in several different neurodegenerative diseases could be the direct production of H2O2 during the early stages of protein aggregation.

Post-traumatic stress disorder symptoms following a head injury: does amnesia for the event influence the development of symptoms?

BACKGROUND: There is controversy as to whether PTSD can develop following a brain injury with a loss of consciousness. However, no studies have specifically examined the influence of the memories that the individuals may or may not have on the development of symptoms. AIMS: To consider how amnesia for the traumatic event effects the development and profile of traumatic stress symptoms. METHOD: Fifteen hundred case records from an Accident and Emergency Unit were screened to identify 371 individuals with traumatic brain injury who were sent questionnaires by post. The 53 subsequent valid responses yielded three groups: those with no memory (n = 14), untraumatic memories (n = 13) and traumatic memories (n = 26) of the index event. The IES-R was used as a screening measure followed by a structured interview (CAPS-DX) to determine caseness and provide details of symptom profile. RESULTS: Groups with no memories or traumatic memories of the index event reported higher levels of psychological distress than the group with untraumatic memories. Ratings of PTSD symptoms were less severe in the no memory groups compared to those with traumatic memories. CONCLUSIONS: Psychological distress was associated with having traumatic or no memories of an index event. Amnesia for the event did not protect against PTSD; however, it does appear to protect against the severity and presence of specific intrusive symptoms.

New evidence that the Alzheimer beta-amyloid peptide does not spontaneously form free radicals: an ESR study using a series of spin-traps.

The direct formation of free radicals from Abeta has been suggested to be a key neurotoxic mechanism in Alzheimer's disease (AD). We have explored the possibility of the spontaneous formation of peptide-derived free radicals during the incubation of Abeta 1-40 by ESR spectroscopy using N-tert-butyl-alpha-phenylnitrone (PBN), 5,5-dimethyl-1-pyrroline N-oxide (DMPO), alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), and 3,5-dibromo-4-nitrosobenzenesulfonic acid sodium salt (DBNBS) as spin traps. Employing PBN, we observed spectra during the incubation of beta-amyloid peptide, at 37 degrees C, which included adducts of 2-methyl-2-nitrosopropane (MNP), despite rigorous purification of the PBN before incubation. The formation of some of these adducts was found to be enhanced by ambient laboratory light. Our experiments have led us to propose a hypothesis that PBN undergoes hydrolysis and decomposition in the presence of oxidants, which explains the origin of all of the PBN and MNP adducts observed (even when the PBN is highly purified). Hydrogen peroxide, formed during incubation, could play a major role as an oxidant in these experiments. Of the other three spin traps, only DMPO gave (very weak) spectra, but these could be assigned to its hydroxyl radical adduct, formed as an artifact by the nucleophilic addition of water to DMPO, catalyzed by trace levels of iron ions. Thus, while spectra are observed during our experiments, none of them can be assigned to adducts of radicals derived from the peptide and, therefore, our data do not support the suggestion that radicals are spontaneously formed from beta-amyloid peptide.

alpha-Synuclein implicated in Parkinson's disease catalyses the formation of hydrogen peroxide in vitro.

Some rare inherited forms of Parkinson's disease (PD) are due to mutations in the gene encoding a 140-amino acid presynaptic protein called alpha-synuclein. In PD, and some other related disorders such as dementia with Lewy bodies, alpha-synuclein accumulates in the brain in the form of fibrillar aggregates, which are found inside the neuronal cytoplasmic inclusions known as Lewy bodies. By means of an electron spin resonance (ESR) spin trapping method, we show here that solutions of full-length alpha-synuclein, and a synthetic peptide fragment of alpha-synuclein corresponding to residues 61-95 (the so-called non-Abeta component or NAC), both liberate hydroxyl radicals upon incubation in vitro followed by the addition of Fe(II). We did not observe this property for the related beta- and gamma-synucleins, which are not found in Lewy bodies, and are not linked genetically to any neurodegenerative disorder. There is abundant evidence for the involvement of free radicals and oxidative stress in the pathogenesis of nigral damage in PD. Our new data suggest that the fundamental molecular mechanism underlying this pathological process could be the production of hydrogen peroxide by alpha-synuclein.

3-p-Toluoyl-2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran and 2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran do not act as surfactants or micelles when inhibiting the aggregation of beta-amyloid peptide.

The cmc and IC50 values of the beta-amyloid (Abeta) aggregation inhibitors, 3-p-toluoyl-2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran 1, and 2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran 2 have been determined. After comparison of the cmc data and biological data (IC50 values), we conclude that these active benzofurans do not act as surfactants or micelles at the concentration required to inhibit beta-amyloid-peptide aggregation.

Production of reactive oxygen species from aggregating proteins implicated in Alzheimer's disease, Parkinson's disease and other neurodegenerative diseases.

The deposition of abnormal protein fibrils is a prominent pathological feature of many different 'protein conformational' diseases, including some important neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), motor neurone disease and the 'prion' dementias. Some of the fibril-forming proteins or peptides associated with these diseases have been shown to be toxic to cells in culture. A clear understanding of the molecular mechanisms responsible for this toxicity should shed light on the probable link between protein deposition and cell loss in these diseases. In the case of the beta-amyloid (Abeta), which accumulates in the brain in AD, there is good evidence that the toxic mechanism involves the production of reactive oxygen species (ROS). By means of an electron spin resonance (ESR) spin-trapping method, we have shown recently that solutions of Abeta liberate readily detectable amounts of hydroxyl radicals upon incubation in vitro followed by the addition of small amounts of Fe(II). We have also obtained similar results with alpha-synuclein, which accumulates in Lewy bodies in PD. Our data suggest that hydrogen peroxide accumulates during Abeta or alpha-synuclein incubation and that this is subsequently converted to hydroxyl radicals, on addition of Fe (II), by Fenton's reaction. Consequently, we now support the idea that one of the fundamental molecular mechanisms underlying the pathogenesis of cell death in AD, PD, and possibly some other protein conformational diseases, could be the direct production of ROS during formation of the abnormal protein aggregates. This hypothesis suggests a novel approach to the therapy of this group of diseases.

Attachment in anorexia nervosa: a transgenerational perspective.

Both clinical and empirical studies suggest that insecure attachment is common in eating disordered populations. Clinical studies have addressed mother-daughter interactions, but there has been little empirical research into the mother's own attachment patterns and whether there might be intergenerational transmission of these patterns. We aimed to examine the attachment status of patients with severe anorexia nervosa and their mothers, using the 'gold standard' Adult Attachment Interview (AAI). We predicted: (1) a high level of insecurity among the patients (women with anorexia nervosa with or without bulimic behaviours); (2) that the mothers would show a higher rate of insecurity than predicted by population norms; and (3) that there might be attachment style associations within mother-daughter pairs. Twenty consecutive in-patients with a DSM-IV diagnosis of anorexia nervosa were interviewed using the AAI, as were 12 of their mothers. The mental state of daughters was rated by experienced clinicians, and that of mothers by the Clinical Interview Schedule (Revised). AAIs were transcribed and rated by expert raters. Nineteen (95%) daughters and 10 (83%) mothers were rated insecure on the AAI. Of these, 15 (79%) daughters and seven (70%) mothers were dismissive in type. We did not find an association between mothers' and daughters' attachment style. The incidence of unresolved loss was high among the mothers (67%). Idealization scores were high and reflective functioning scores low in both mother and daughter groups. Women with anorexia nervosa and their mothers commonly have a dismissive attachment style. Low levels of reflective functioning and high idealization scores are found in both groups, and may be learned (or transmitted) from mother to daughter. A difficulty in emotional processing, exemplified by unresolved loss, may be transmitted to daughters, and act as a risk factor for the development of anorexia nervosa.

Attachment patterns in eating disorders: past in the present.

OBJECTIVE: There is a wide literature suggesting abnormal mother-daughter and familial attachment patterns in individuals with eating disorders. We surmised that this insecurity would extend to adult attachment relationships. METHODS: The Reciprocal Attachment Questionnaire (RAQ) was administered to all inpatients and outpatients at a tertiary referral eating disorders unit over a given period of time, and to controls. The RAQ operationalizes the key components of reciprocal attachment, and is in close theoretical agreement with the Adult Attachment Interview. RESULTS: Patients scored significantly higher than controls on most scales of the RAQ, most notably on Compulsive Care-Seeking and Compulsive Self-Reliance. We did not find any associations between eating disorder diagnoses and particular attachment profiles. CONCLUSIONS: A basic "pull-push" dilemma was demonstrated in the reciprocal attachment relationships of eating-disordered subjects. This dilemma bedevils attempts at therapy and may illuminate the strong feelings elicited by these patients in their therapists. The association of attachment style with particular disorder subgroup diagnoses is complicated. Childhood attachment insecurity may provide a vulnerability whose symptomatic manifestation is colored by later events.

Predictors of outcome for two treatments for bulimia nervosa: short and long-term.

OBJECTIVE: This study examined pretreatment variables to predict outcome in two treatments for bulimia nervosa. METHOD: Patients were offered either 16 weeks of cognitive-behavioral therapy (CBT) or a self-treatment manual followed by up to 8 weeks of CBT (sequential group). Using complete data, stepwise regression analyses were performed. RESULTS: It was found that a longer duration of illness and lower binge frequency predicted a better outcome both at the end of treatment (p < .001) and at 18 months of follow-up (p < .005). In the sequential group, lower pretreatment binge frequency predicted better outcome at the end of treatment (p < .05) and at 18 months of follow-up (p < .05). In the CBT group, longer duration of illness predicted better outcome at the end of treatment (p < .02). DISCUSSION: It is concluded that (1) those with more frequent binging may require a more intense intervention and (2) those who have been ill longer may be more motivated to respond to treatment.

The demand for eating disorder care. An epidemiological study using the general practice research database.

BACKGROUND: An epidemiological study of anorexia nervosa and bulimia nervosa in primary care was performed using the General Practice Research Database (GPRD). METHOD: The GPRD was screened between 1988 and 1994 for newly diagnosed cases of anorexia nervosa and bulimia nervosa. The validity of the computer diagnosis was established by obtaining clinical details from a random sample of the general practitioners (GPs). RESULTS: Incidence rates for detection of cases by GPs in 1993 was 4.2 per 100,000 population for anorexia nervosa, and 12.2 per 100,000 for bulimia nervosa. The relative risks of females to males was 40:1 for anorexia nervosa and 47:1 for bulimia nervosa. A threefold increase in the recording of bulimia nervosa was found from 1988 to 1993. Eighty per cent of anorexia nervosa cases and 60% of bulimia nervosa cases were referred to secondary care. CONCLUSION: There is a continuing expansion of service need for bulimia nervosa. The majority of cases of eating disorders are referred to secondary services. There is scope for more effective management of bulimia nervosa in primary care.

Sequential treatment for bulimia nervosa incorporating a self-care manual.

BACKGROUND: The aim of this study was to evaluate the effectiveness of a stepped care approach to the treatment of bulimia nervosa: a self-care manual followed, if necessary, by a course of attenuated cognitive behavioural treatment (CBT) in comparison with standard CBT. METHOD: One hundred and ten patients, presenting at a tertiary referral centre with ICD-10 bulimia nervosa or atypical bulimia nervosa, were randomly assigned to one of two treatment conditions; a) a sequential treatment group: 8 weeks with a self-care manual followed by up to eight sessions of CBT (if still symptomatic) or b) 16 sessions of CBT. RESULTS: Bulimic symptoms improved significantly in both groups with no significant differences between the two groups on any of the measures at the end of treatment or at 18 months follow-up. At end of treatment 30% (95% CI: 18-46%) of the sequential group and 30% (95% CI: 17-47%) of the standard treatment group were free from all bulimic symptoms. Sixteen of those in the sequential group improved significantly with self-care and did not require additional treatment. The median number of sessions taken by the sequential group was three (95% CI: 0-6). At 18 months follow-up 40% (95% CI: 23-59%) of the sequential group and 41% (95% CI: 25-59%) of the CBT group were symptom free. CONCLUSIONS: A sequential approach to the treatment of bulimia may be as effective as standard CBT and can considerably reduce the amount of therapist contact required.

The effect of signal onset/offset envelope on underwater detection thresholds of a harbor seal (Phoca vitulina).

The effects of signal onset/offset envelope on the underwater hearing thresholds of a harbor seal (Phoca vitulina) were measured. Pure-tone, 540-ms pulses at 2, 4, 8, and 16 kHz were presented as test signals. An ANOVA revealed that there were no significant differences between repeated threshold measures for abrupt onset/offset signal envelopes versus slow onset/offset signal envelopes [F = 4.380, d.f. = (1,18), p > 0.05]. Seal vocalizations which have an abrupt onset/offset may be serving a short-range communicative function by helping the listener determine the direction of a nearby sender.

Descending frequency swept tones have lower thresholds than ascending frequency swept tones for a harbor seal (Phoca vitulina) and human listeners.

Many seal vocalizations consist of frequency swept tones. The signal detection thresholds of a harbor seal (Phoca vitulina) and of human listeners were measured using ascending and descending frequency swept tones at 1/3- and 1-oct bandwidths. The swept tones increased or decreased exponentially and traversed the same frequency range. The sweeps were centered on 2, 4, and 8 kHz for the seal study and 0.5, 1, and 2 kHz for the human listeners. The bandwidth of the sweep did not affect signal detection abilities of either the seal or human listeners. The seal had lower signal detection thresholds (1-5 dB) when presented with the descending frequency swept tones (F = 32.04, df = (1,31), p < 0.000001). Human listeners also had lower detection thresholds for descending frequency swept tones (t = -4.78, df = 52, p < 0.0001). Pinniped ascending frequency swept calls may not function as well as descending frequency sweeps for long-distance communicative signals.

Production of monoclonal anti-idiotype antibodies which mimic an M-like protein of Streptococcus equi.

Rat monoclonal anti-idiotype antibodies (mAb2) were raised against two mouse monoclonal antibodies (mAb1), 1D10 and 2A6, with specificity for the M-like protein of Streptococcus equi. The capacity of the mAb2 to inhibit the binding between the corresponding mouse mAb1 against which the mAb2 were raised and the M-like protein was investigated in an inhibition EIA. One of the ten mAb2 examined, namely 5D1 (anti-mAb1 1D10), was able to inhibit this binding. The mAb2 5D1 bound to the mAb1 1D10 in such a way as to completely inhibit the subsequent binding of the M-like protein antigen to the paratope of the mAb1 1D10. The mAb2 5D1 is likely to represent a true image of the M-like protein antigen and may thus be described as an Ab2 beta anti-idiotype antibody.