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Aim: The British Thyroid Association (BTA) Guidelines for the Management of Thyroid Cancer advocate for fine-needle aspiration cytology for all thyroid nodules graded indeterminate (U3) at ultrasound assessment. This approach raises concerns regarding potential over-diagnosis of low-risk lesions. Conversely, equivalent Thyroid Imaging Reporting and Data Systems (TIRADS) guidelines permit surveillance or discharge of indeterminate thyroid nodules of certain sizes. This service analysis analyses how guideline choice impacts the fine-needle aspiration cytology rate and subsequent surgical management of indeterminate thyroid nodules., Materials and Methods: All patients with an indeterminate (U3) thyroid nodule identified on ultrasound over a 12-month period were included. Indeterminate thyroid nodules were retrospectively rescored using three equivalent TIRADS classifications by three independent reviewers, blinded to the histopathology. Hypothetical differences in fine-needle aspiration cytology rates and surgical activity were then compared., Results: Ninety-six nodules were identified. Retrospective application of TIRADS guidelines resulted in a hypothetical 44.8-55.2% reduction in fine-needle aspiration cytology performed for indeterminate thyroid nodules compared to BTA. A statistically significant increase in rates of surgical activity for indeterminate thyroid nodules was observed between BTA guidance and all retrospectively applied TIRADS guidelines (p < 0.001). Of four confirmed thyroid cancers, three would have been unanimously removed., Conclusion: Under BTA guidance, increased fine-needle aspiration cytology rates for indeterminate thyroid nodules resulted in significantly increased surgical activity in our cohort compared to retrospectively applied TIRADS guidelines., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: The human ZFP57 gene is a major regulator of imprinted genes, maintaining DNA methylation marks that distinguish parent-of-origin-specific alleles. DNA methylation of the gene itself has shown sensitivity to environmental stimuli, particularly folate status. However, the role of DNA methylation in ZFP57's own regulation has not been fully investigated., Methods: We used samples and data from our previously described randomised controlled trial (RCT) in pregnancy called Folic Acid Supplementation in the Second and Third Trimester (FASSTT), including follow-up of the children at age 11. Biometric and blood biochemistry results were examined for mothers and children. Methylation of ZFP57 was analysed by EPIC arrays, pyrosequencing and clonal analysis, and transcription assessed by PCR-based methods. Functional consequences of altered methylation were examined in cultured cells with mutations or by inhibition of the main DNA methyltransferases. DNA variants were examined using pyrosequencing and Sanger sequencing, with results compared to published studies using bioinformatic approaches. Cognitive outcomes were assessed using the Wechsler Intelligence Scale for Children 4th UK Edition (WISC-IV), with neural activity during language tasks quantified using magnetoencephalography (MEG)., Results: Here we show that methylation at an alternative upstream promoter of ZFP57 is controlled in part by a quantitative trait locus (QTL). By altering DNA methylation levels, we demonstrate that this in turn controls the expression of the ZFP57 isoforms. Methylation at this region is also sensitive to folate levels, as we have previously shown in this cohort. Fully methylated alleles were associated with poorer performance in the Symbol Search and Cancellation subtests of WISC-IV in the children at age 11 years. There were also differences in neural activity during language tasks, as measured by MEG. Analysis of published genome-wide studies indicated other SNPs in linkage disequilibrium with the mQTL were also associated with neurodevelopmental outcomes., Conclusions: While numbers in the current RCT were small and require further validation in larger cohorts, the results nevertheless suggest a molecular mechanism by which maternal folic acid supplementation during pregnancy may help to counteract the effects of folate depletion and positively influence cognitive development in the offspring., Competing Interests: Declarations. Ethics approval and consent to participate: The Office for Research Ethics Committee for Northern Ireland (ORECNI) has granted ethical approval for the original randomised controlled FASSTT trial (ref:05/Q2008/21) and for the follow-up FASSTT Offspring Trial (12/NI/0077). Ulster University Research Ethics Committee also approved the FASSTT Off spring Trial (UUREC: 12/0121). Written informed consent from the mother and assent from the child were obtained. The trials were registered at ISRCTN Registry (ISRCTN19917787). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The term athlete does not currently have an agreed definition or standardized use across the literature. We analyzed the use of the term "athlete" amongst review studies specific to Anterior Cruciate Ligament (ACL) rehabilitation to investigate if the term was justified in its use. A comprehensive review of a database was performed to identify review papers which used the term "athlete" in the title, and which were related to ACL rehabilitation and surveillance. These papers were analyzed and their source papers were extracted for review. Twenty-eight review papers were identified. Source studies were extracted and analyzed. After removal of duplicates 223 source papers were identified. Despite using the term "athlete" in the review study titles only 5/17 (10.7%) sufficiently justified the use of this term. The term athlete was used in 117/223 (52.5%) of the source studies. Of those, 78/117 source studies (66.7%) justified the term athlete. The remaining 39/117 (33.3%) papers where participants were stated to be athletes, gave no justification. The ambiguous use of the term athlete amongst published studies highlights the need for a definition or justification of the term to be used in studies. The lack of a standard definition leads to the potential for studies to dilute high quality data by the potentially differing rehabilitation requirements and access to resources available to those with varying exercise levels. The indiscriminate use of the term athlete could lead to participants with widely ranging physical activity levels being included in the same study, and being used to create clinical advice for all. Advice could potentially vary across those of differing physical activity levels., (© 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Suboptimal status of folate and/or interrelated B vitamins (B 12 , B 6 and riboflavin) can perturb one-carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate-related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence-based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition-epigenome-brain relationship, particularly focussing on folate-related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio-banked samples from existing well-characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition-epigenome-brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state-of-the-art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle., (© 2023 The Authors. Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

The SNO+ Collaboration reports the first evidence of reactor antineutrinos in a Cherenkov detector. The nearest nuclear reactors are located 240 km away in Ontario, Canada. This analysis uses events with energies lower than in any previous analysis with a large water Cherenkov detector. Two analytical methods are used to distinguish reactor antineutrinos from background events in 190 days of data and yield consistent evidence for antineutrinos with a combined significance of 3.5σ.

Introduction: Pharyngolaryngectomy with jejunal free-flap (JFF) reconstruction can be offered for locally advanced hypopharyngeal cancer. However, the procedure carries significant morbidity. Postoperative serial serum C-reactive protein (CRP) has been shown to be a marker predicting postoperative complications, and the aim of this study was to describe the dynamics and value of CRP in this patient group., Methods: Retrospective analysis of pharyngolaryngectomies with JFF reconstruction was performed in our institution. Daily postoperative CRP values were analysed within the first 14 days, as were complications., Results: Twenty-one cases were included. Total morbidity was 57.1% including 14.3% (temporary) anastomotic leaks and 14.3% flap failures. Patients in the normal group showed peak CRP levels around postoperative day 2 (2.2). Increased CRP levels on or after day 4 were associated with complications ( p <0.01) with a sensitivity of 83.3% and specificity of 77.8%. In keeping with CRP kinetics from other surgical studies, peak CRP values on day 2 or 3 are expected, followed by a decline. Peaks in CRP on day 4 or later raise the suspicion of complications. CRP is not specific for any one complication but rather can help guide early appropriate clinical assessment and management., Conclusions: The natural postoperative CRP response peaks around postoperative day 2 (2.2) and declines thereafter. Rising CRP levels after postoperative day 3 are suspicious of surgical complications ( p <0.01) with positive and negative predictive values of 83.3% and 77.8%, respectively. Therefore, serial postoperative CRP can be used as an adjunct to monitor outcomes in this group.

Background: The COVID-19 pandemic in 2020 resulted in the older population being asked to remain at home and avoid other people outside their household. This could have implications for both receipt and provision of informal caring., Objective: To determine if informal care provision by older carers changed during the first wave of the COVID-19 pandemic from pre-pandemic care and if this was associated with a change in mental health and well-being of carers., Design and Setting: Longitudinal nationally representative study of community dwelling adults from The Irish Longitudinal Study on Ageing (TILDA) (Waves 3-COVID-Wave 6)., Methods: We studied a cohort of 3670 adults aged ≥60 in Ireland during the COVID-19 pandemic (July-November 2020) and compared with previous data collections from the same cohort between 2014-2018. Independent variables were caregiving status and caregiving intensity, outcome measures included depressive symptoms (CES-D8), Perceived Stress (PSS4) and Quality of life (CASP12). Mixed models adjusting for socio-demographics and physical health were estimated., Results: Caregiving increased from 8.2% (2014) to 15.4% (2020). Depression, and stress scores increased while quality of life decreased for all participants. Carers reported poorer mental health, and higher caring hours were associated with increased depression and stress and decreased quality of life scores on average, and increased depression was higher for women., Conclusions: Informal caregiving increased during the pandemic and family caregivers reported increased adverse mental health and well-being and this continued throughout the early months of the pandemic. The disproportionate burden of depression was highest in women providing higher caring hours., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: To identify, appraise, and describe studies focussing on the nutritional characteristics of people experiencing homelessness (PEH)., Study Design: Systematic (narrative) review., Methods: We identified full-text studies of any design and in the English language of adults (≥18 years) fulfilling the European Typology criteria for homelessness, based in community or hospital settings, and which report nutritional measures. Five electronic databases, 13 grey literature sources, reference lists, and forward citations were searched. Data on study characteristics and nutrition measures were collected and synthesised narratively. Risk of bias was assessed using relevant checklists for each study type., Results: A total of 1130 studies were identified and retrieved. After screening, six studies were included for review: three cross-sectional studies; two case-control studies; and one randomised control trial, involving a total of 1561 participants from various settings including shelters, drop-in centres, hospitals, and hostels. All included studies were from high-income countries. Studies reported a range of nutrition measures including anthropometry (e.g., body mass index (BMI)), serum micronutrients and biomarkers, and dietary intake. Between 33.3% and 68.3% of participants were overweight or obese; 3.5%-17% were underweight; and low blood levels of iron, folate, vitamins C, D, and B12, and haemoglobin were prevalent. PEH consumed high amounts of dietary fats and alcohol, and low amounts of fruits and vegetables compared with national guidelines and housed individuals. There was moderate to high risk of selection and measurement bias and confounding in included studies., Conclusions: A majority of PEH are within unhealthy BMI ranges and are deficient in serum micronutrients and nutritional biomarkers. Studies using large data sets that examine multiple aspects of nutrition are needed to describe the nutritional characteristics of PEH., Registration: This systematic review is based on a prespecified protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO CRD42021218900)., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Dark matter with Planck-scale mass (≃10^{19}  GeV/c^{2}) arises in well-motivated theories and could be produced by several cosmological mechanisms. A search for multiscatter signals from supermassive dark matter was performed with a blind analysis of data collected over a 813 d live time with DEAP-3600, a 3.3 t single-phase liquid argon-based detector at SNOLAB. No candidate signals were observed, leading to the first direct detection constraints on Planck-scale mass dark matter. Leading limits constrain dark matter masses between 8.3×10^{6} and 1.2×10^{19}  GeV/c^{2}, and ^{40}Ar-scattering cross sections between 1.0×10^{-23} and 2.4×10^{-18}  cm^{2}. These results are interpreted as constraints on composite dark matter models with two different nucleon-to-nuclear cross section scalings.

Background: There is minimal information on the utilisation of Disease Modifying Treatment (DMTs) for multiple sclerosis. The appropriate and safe use of medicines is informed by utilisation studies. Outcomes can inform health interventions to improve appropriate use of medicines and post marketing surveillance activities to improve safety., Objective: To evaluate utilisation and treatment patterns of disease modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS)., Methods: A representative sample of the Australian pharmaceutical benefits scheme data were analysed (2006-2016). Demographics of incident users and trends in incident and prevalent users were determined. Individual patient treatment pathways were determined by sequential initiation of medicines in two different periods (2006-2013 and 2014-2019)., Results: There were 20,660 patients with at least one dispensing of a DMT for RRMS during the study period (median age 41 years, 75% female). Incident and prevalent use increased by 20% and 88%, respectively. The market was responsive to 13 new listings of DMTs over the study period. Sequential treatment was found for 66% of initiators in 2006-2013 and 28.5% of initiators in 2014-2019. Diverse treatment pathways were found, with 278 and 93 unique sequences in 2006-2013 and 2014-2019, respectively., Conclusion: The availability of new DMTs has influenced both initial treatment choice and prevalence of users. Individualised treatment patterns and exposure to multiple medicines over time will challenge traditional pharmacovigilance systems., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cocooning or shielding, i.e. staying at home and reducing face-to-face interaction with other people, was an important part of the response to the COVID-19 pandemic for older people. However, concerns exist regarding the long-term adverse effects cocooning may have on their physical and mental health., Aim: To examine health trajectories and healthcare utilization while cocooning in a cohort of community-dwelling people aged ≥70 years., Design: Survey of 150 patients (55% female, mean age 80 years and mean Clinical Frailty Scale Score 4.8) attending ambulatory medical services in a large urban university hospital., Methods: The survey covered four broad themes: access to healthcare services, mental health, physical health and attitudes to COVID-19 restrictions. Survey data were presented descriptively., Results: Almost 40% (59/150) reported that their mental health was 'worse' or 'much worse' while cocooning, while over 40% (63/150) reported a decline in their physical health. Almost 70% (104/150) reported exercising less frequently or not exercising at all. Over 57% (86/150) of participants reported loneliness with 1 in 8 (19/150) reporting that they were lonely 'very often'. Half of participants (75/150) reported a decline in their quality of life. Over 60% (91/150) agreed with government advice for those ≥70 years but over 40% (61/150) reported that they disliked the term 'cocooning'., Conclusions: Given the likelihood of further restrictions in coming months, clear policies and advice for older people around strategies to maintain social engagement, manage loneliness and continue physical activity and access timely medical care and rehabilitation services should be a priority., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Association of Physicians.)

Objective: To describe the incidence, morphology and clinical significance of congenital vertebral malformations (CVM) in two breeds of brachycephalic dogs presenting to a referral veterinary hospital., Design: Prospective cohort study series., Materials and Methods: Forty-nine French Bulldogs and Pugs were prospectively evaluated and placed in one of two groups based on whether or not they presented for neurological signs referable to spinal cord disease. A computed tomography (CT) of their entire spine was obtained and the presence and classification of CVM along with the degree of spinal kyphosis recorded for all dogs. Statistical analysis was performed to identify clinical associations between these factors (P < 0.05)., Results: CVM were prevalent across both breeds with the French Bulldog having more malformations than the Pug (Kruskal-Wallis nonparametric analysis of variance, P < 0.0001). Breed associated vertebral malformation subtypes included butterfly subtype in French Bulldogs (Chi-square, P = 0.0002), and transitional subtype in Pugs (odds ratio, 22.7; P = 0.000). A new subtype, dorsal wedge, was observed in 12 cases. The presence, number and subtype of vertebral malformation were not reliable for predicting the development of neurological signs across both breeds (Chi-square, P > 0.05). However, spinal kyphosis >35° calculated via Cobb angle was associated with Pugs that had neurological deficits (Chi-square, P = 0.028)., Conclusions: Congenital vertebral malformations largely appear to be incidental findings in this population of French Bulldogs but are of more significance in the Pug breed when spinal kyphosis is >35°. French Bulldogs that have spinal cord disease and CVM are more likely to have pathology distant to CVM with intervertebral disc herniation most common., (© 2021 Australian Veterinary Association.)

Objectives: Schools in the Republic of Ireland reopened to students and staff in late August 2020. We sought to determine the test positivity rate of close contacts of cases of coronavirus disease 2019 (COVID-19) in schools during the first half-term of the 2020/2021 academic year., Methods: National-level data from the schools' testing pathway were interrogated to determine the positivity rate of close contacts of cases of COVID-19 in Irish primary, postprimary and special schools during the first half-term of 2020/2021 academic year. The positivity rates among adult and child close contacts were compared and the proportion of national cases of COVID-19 who were aged 4-18 years during the observation period was calculated to assess whether this proportion increased after schools reopened., Results: Of all, 15,533 adult and child close contacts were tested for COVID-19 through the schools' testing pathway during the first half-term of the 2020/2021 academic year. Three hundred and ninety-nine close contacts tested positive, indicating a positivity rate of 2.6% (95% confidence interval: 2.3-2.8%). The positivity rates of child and adult close contacts were similarly low (2.6% vs 2.7%, P = 0.7). The proportion of all national cases of COVID-19 who were aged 4-18 years did not increase during the first half-term of the 2020/2021 school year., Conclusions: The low positivity rate of close contacts of cases of COVID-19 in schools indicate that transmission of COVID-19 in Irish schools during the first half-term of the 2020/2021 academic year was low. These findings support policies to keep schools open during the pandemic., (Copyright © 2021 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

The DEAP-3600 detector searches for the scintillation signal from dark matter particles scattering on a 3.3 tonne liquid argon target. The largest background comes from 39 Ar beta decays and is suppressed using pulse-shape discrimination (PSD). We use two types of PSD estimator: the prompt-fraction, which considers the fraction of the scintillation signal in a narrow and a wide time window around the event peak, and the log-likelihood-ratio, which compares the observed photon arrival times to a signal and a background model. We furthermore use two algorithms to determine the number of photons detected at a given time: (1) simply dividing the charge of each PMT pulse by the mean single-photoelectron charge, and (2) a likelihood analysis that considers the probability to detect a certain number of photons at a given time, based on a model for the scintillation pulse shape and for afterpulsing in the light detectors. The prompt-fraction performs approximately as well as the log-likelihood-ratio PSD algorithm if the photon detection times are not biased by detector effects. We explain this result using a model for the information carried by scintillation photons as a function of the time when they are detected., (© The Author(s) 2021.)

Objectives: To describe a cross-border foodborne outbreak of Shigella sonnei that occurred in Ireland and Northern Ireland (NI) in December 2016 whilst also highlighting the valuable roles of sales data and international collaboration in the investigation and control of this outbreak., Study Design: A cross-border outbreak control team was established to investigate the outbreak., Methods: Epidemiological, microbiological, and environmental investigations were undertaken. Traditional analytical epidemiological studies were not feasible in this investigation. The restaurant chain provided sales data, which allowed assessment of a possible increased risk of illness associated with exposure to a particular type of heated food product (product A)., Results: Confirmed cases demonstrated sole trimethoprim resistance: an atypical antibiogram for Shigella isolates in Ireland. Early communication and the sharing of information within the outbreak control team facilitated the early detection of the international dimension of this outbreak. A joint international alert using the European Centre for Disease Control's confidential Epidemic Intelligence Information System for Food- and Waterborne Diseases and Zoonoses (EPIS-FWD) did not reveal further cases outside of the island of Ireland. The outbreak investigation identified that nine of thirteen primary case individuals had consumed product A from one of multiple branches of a restaurant chain located throughout the island of Ireland. Product A was made specifically for this chain in a food production facility in NI. S. sonnei was not detected in food samples from the food production facility. Strong statistical associations were observed between visiting a branch of this restaurant chain between 5 and 9 December 2016 and eating product A and developing shigellosis., Conclusions: This outbreak investigation highlights the importance of international collaboration in the efficient identification of cross-border foodborne outbreaks and the value of using sales data as the analytical component of such studies., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Aim: We determined the safety, feasibility and sustainability of an outpatient model of care for infants exposed to intra-uterine drugs., Methods: This was a retrospective chart review of 774 drug-exposed infants born between 1998 and 2016 at the Royal Hospital for Women, Sydney, Australia., Results: Most (86%) of the mothers used multiple drugs, including opioids (58%). More than three-quarters (78%) of the infants were born full term at a mean gestation of 38 weeks and hospitalised for a median of seven days. This rose to 14 days if they were medicated for neonatal abstinence syndrome (NAS). Most of the NAS patients (83%) were discharged on medication, namely morphine, and the median duration of NAS treatment was 76 (interquartile range 35-120). Three medication errors occurred: two extra doses of phenobarbitone and one infant weaned off morphine faster than prescribed. No infants were rehospitalised for NAS. Four died from sudden infant death syndrome at 2.2-5.8 months after discharge and one drowned at 15 months. None were medicated at the time of death., Conclusion: Outpatient care for drug-exposed infants was sustainable and had low complication rates, even for those with NAS. The optimum duration of follow-up and impact on hospital costs should be examined., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Purpose: To test whether ill-health is associated with a decrease in quality of life (QoL) over time and if positive social circumstances are beneficial to QoL, using the shorter form CASP-12 in a sample drawn from a nationally representative cohort of older adults. To do so, the association between factors from a number of life domains and QoL was investigated., Methods: Data were from the first three waves of The Irish Longitudinal Study on Ageing, a prospective nationally representative study of community dwelling older adults in the Republic of Ireland. QoL was measured using the shorter form CASP-12 and the latent growth curve method was used to describe within- and between-person variation in longitudinal QoL trajectories., Results: There was considerable variation in QoL scores cross-sectionally and longitudinally. QoL did not decline linearly with age but increased from age 50 and peaked at 68 years before declining in older age. QoL differed significantly between individuals and decreased over time. A variety of demographic, health, and social characteristics were associated with changes in QoL over time. These included cohabiting; self-rated health; functional limitations; fear of falling; mental health; loneliness; social networks; social activities; caring for grandchildren; income; and death of a spouse., Conclusions: Changes in QoL over time were not merely a function of ageing, or declining health but resulted from factors from a variety of domains with loneliness and social participation particularly important. Policies concerned with successful ageing and QoL among older adults must consider social circumstances as well as physical and psychological well-being.

Aim: To evaluate the association between gestational weight gain (GWG) in early pregnancy and incidence of abnormal glucose tolerance (AGT) and gestational diabetes mellitus (GDM) among Latinas., Methods: We conducted a retrospective cohort study of 2039 Latinas using pooled data from two medical centres in Massachusetts. Gestational weights were abstracted from medical records and GWG was categorized as low, appropriate and excessive according to 2009 Institute of Medicine Guidelines. Diagnosis of AGT and GDM was confirmed by study obstetricians., Results: A total of 143 women (7.0%) were diagnosed with GDM and 354 (17.4%) with AGT. After adjusting for age and study site, women with low GWG up to the time of GDM screen had a lower odds of GDM (OR: 0.51, 95% CI: 0.29-0.92). Among overweight women, women with excessive first-trimester GWG had 2-fold higher odds of AGT (OR: 1.96, 95% CI: 1.17-3.30) and GDM (OR: 2.07, 95% CI: 1.04-4.12) compared to those with appropriate GWG; however, these findings were not significant among normal weight or obese women., Conclusion: Among Latinas, low GWG up to the time of GDM screen was associated with lower odds of AGT and GDM, while excessive GWG among overweight women was associated with higher odds. Findings highlight need for interventions in early pregnancy to help women meet GWG guidelines and to moderate GWG among overweight Latinas., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Introduction: Termination of resuscitation guidelines for out-of-hospital cardiac arrest can identify patients in whom continuing resuscitation has little chance of success. This study examined the outcomes of patients transferred to hospital with ongoing CPR. It assessed outcomes for those who would have met the universal prehospital termination of resuscitation criteria (no shocks administered, unwitnessed by emergency medical services, no return of spontaneous circulation)., Methods: A retrospective cohort study of consecutive adult patients who were transported to hospital with ongoing CPR was conducted at three hospitals in the West Midlands, UK between September 2016 and November 2017. Patient characteristics, interventions and response to treatment (ROSC, survival to discharge) were identified., Results: 227 (median age 69 years, 67.8% male) patients were identified. 89 (39.2%) met the universal prehospital termination of resuscitation criteria. Seven (3.1%) were identified with a potentially reversible cause of cardiac arrest. After hospital arrival, patients received few specialist interventions that were not available in the prehospital setting. Most (n = 210, 92.5%) died in the emergency department. 17 were admitted (14 to intensive care), of which 3 (1.3%) survived to hospital discharge. There were no survivors (0%) in those who met the criteria for universal prehospital termination of resuscitation., Conclusion: Overall survival amongst patients transported to hospital with ongoing CPR was very poor. Application of the universal prehospital termination of resuscitation rule, in patients without obvious reversible causes of cardiac arrest, would have allowed resuscitation to have been discontinued at the scene for 39.2% of patients who did not survive., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This Letter reports the first results of a direct dark matter search with the DEAP-3600 single-phase liquid argon (LAr) detector. The experiment was performed 2 km underground at SNOLAB (Sudbury, Canada) utilizing a large target mass, with the LAr target contained in a spherical acrylic vessel of 3600 kg capacity. The LAr is viewed by an array of PMTs, which would register scintillation light produced by rare nuclear recoil signals induced by dark matter particle scattering. An analysis of 4.44 live days (fiducial exposure of 9.87 ton day) of data taken during the initial filling phase demonstrates the best electronic recoil rejection using pulse-shape discrimination in argon, with leakage <1.2×10^{-7} (90% C.L.) between 15 and 31  keV&#95;{ee}. No candidate signal events are observed, which results in the leading limit on weakly interacting massive particle (WIMP)-nucleon spin-independent cross section on argon, <1.2×10^{-44}  cm^{2} for a 100  GeV/c^{2} WIMP mass (90% C.L.).

The characteristics of indoor light (intensity, spectral, spatial distribution) originating from outdoors have been studied using experimental and modeling tools. They are influenced by many parameters such as building location, meteorological conditions, and the type of window. They have a direct impact on indoor air quality through a change in chemical processes by varying the photolysis rates of indoor pollutants. Transmittances of different windows have been measured and exhibit different wavelength cutoffs, thus influencing the potential of different species to be photolysed. The spectral distribution of light entering indoors through the windows was measured under different conditions and was found to be weakly dependent on the time of day for indirect cloudy, direct sunshine, partly cloudy conditions contrary to the light intensity, in agreement with calculations of the transmittance as a function of the zenithal angle and the calculated outdoor spectral distribution. The same conclusion can be drawn concerning the position within the room. The impact of these light characteristics on the indoor chemistry has been studied using the INCA-Indoor model by considering the variation in the photolysis rates of key indoor species. Depending on the conditions, photolysis processes can lead to a significant production of radicals and secondary species., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hepatitis A infection results in a spectrum of illness from asymptomatic disease to severe fulminant hepatitis. Since 2000, <50 cases have been reported annually in Ireland. We report on an outbreak of hepatitis A associated with a childcare facility(CCF) in 2015 in Ireland. Between January and July 2015, 12 outbreak-associated symptomatic hepatitis A cases were identified, including one delayed, retrospective diagnosis. Seven (58%) cases were adults, eight (67%) were male, six of the adults required hospitalisation. All 12 cases were confirmed on serology and the four cases that were genotyped were identical on phylogenetic analysis. Potential environmental exposures and hygiene practices at the CCF were investigated. Outbreak control measures included the provision of: hepatitis A information, infection prevention advice, hepatitis A vaccination to 554 CCF contacts, and voluntary closure of the CCF for deep-cleaning and staff education. From a healthcare perspective1, outbreak control costs were in excess of €45 000. This outbreak illustrates the considerable adult morbidity that can occur in hepatitis A outbreaks, highlights the challenges in controlling a large CCF-associated outbreak and the importance of early recognition by clinicians of hepatitis A.

The Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) trial evaluates the anti-amyloid-β antibody crenezumab in cognitively unimpaired persons who, based on genetic background and age, are at high imminent risk of clinical progression, and provides a powerful test of the amyloid hypothesis. The Neurosciences Group of Antioquia implemented a pre-screening process with the goals of decreasing screen failures and identifying participants most likely to adhere to trial requirements of the API ADAD trial in cognitively unimpaired members of Presenilin1 E280A mutation kindreds. The pre-screening failure rate was 48.2%: the primary reason was expected inability to comply with the protocol, chiefly due to work requirements. More carriers compared to non-carriers, and more males compared to females, failed pre-screening. Carriers with illiteracy or learning/comprehension difficulties failed pre-screening more than non-carriers. With the Colombian API Registry and our prescreening efforts, we randomized 169 30-60 year-old cognitively unimpaired carriers and 83 non-carriers who agreed to participate in the trial for at least 60 months. Our findings suggest multiple benefits of implementing a pre-screening process for enrolling prevention trials in ADAD., Competing Interests: Rios-Romenets, Giraldo-Chica, López, Piedrahita, Ramos, Acosta-Baena, Muñoz, Ospina, Tobón, Lopera, Langbaum, Reiman and Tariot report the funding disclosures above. S. Rios-Romenets receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. M. Giraldo-Chica receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. H. Lopez receives grant and contract support from the NIH, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. F. Piedrahita receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. C. Ramos receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. N. Acosta-Baena receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. C. Muñoz receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. P. Ospina receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. C. Tobon receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. F. Lopera receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. One co-author, a member of the GNA team, is a relative of PSEN1 E280A families. P. Tariot receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation. J. Langbaum receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop. E. Reiman receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation. P. Tariot also reports the following (pertinent for the last two years): consulting fees from Abbott Laboratories, AbbVie, AC Immune, Acadia, Auspex, Boehringer-Ingelheim, Brain Test, Inc., California Pacific Medical Center, Chase Pharmaceuticals, Clintara, CME Inc., Glia Cure, Insys Therapeutics, Pfizer, and T3D; Consulting fees and research support from AstraZeneca, Avanir, Lilly, Lundbeck, Merck and Company, and Takeda; Research support only from Amgen, Avid, Functional Neuromodulation (f(nm)), GE, and Novartis; he is a contributor to a patent owned by the University of Rochester, “Biomarkers of Alzheimer’s disease” and owns stock options in Adamas. J. Langbaum also reports the following (pertinent for the last two years): consulting fees from Biogen and Lilly. E. Reiman also reports: he is a paid research consultant to Alkahest, Alzheon, Axovant, Biogen, Denali, Pfizer, and United Neuroscience and Zinfandel. W. Cho and M. Ward are full time employee of Genentech and are Roche equity holders.

This work aims to contribute to the evidence base regarding the health of those who experience homelessness in Ireland by collating data on methadone use, drug-related deaths and emergency department presentations due to self-harm. Data from the Central Methadone Treatment List (CTL), National Self-Harm Registry Ireland and the National Drug-Related Deaths Index were analysed. The percentage on the CTL registered as being of no fixed abode (NFA) or homeless increased from 2% to 7% from 2011-2014. The absolute number of presentations with deliberate self-harm from those of NFA increased by 49% from 2007-2014. The number of drug-related deaths amongst those of NFA or homeless and who died in Dublin fluctuated from 2004-13 with an overall upward trend. There is an urgent need to adequately resource and coordinate those services which aim to address factors (social and health inequalities, mental ill-health and addiction) which lead people into - and prevent them exiting from - homelessness.

Yttrium iron garnet has a very high Verdet constant, is transparent in the infrared and is an insulating ferrimagnet leading to its use in optical and magneto-optical applications. Its high Q-factor has been exploited to make resonators and filters in microwave devices, but it also has the lowest magnetic damping of any known material. In this article we describe the structural and magnetic properties of single crystal thin-film YIG where the temperature dependence of the magnetisation reveals a decrease in the low temperature region. In order to understand this complex material we bring a large number of structural and magnetic techniques to bear on the same samples. Through a comprehensive analysis we show that at the substrate -YIG interface, an interdiffusion zone of only 4-6 nm exists. Due to the interdiffusion of Y from the YIG and Gd from the substrate, an addition magnetic layer is formed at the interface whose properties are crucially important in samples with a thickness of YIG less than 200 nm.

In this cohort of community dwelling older adults (>60 years), we observed significant positive associations between the frequencies of yogurt intake with measures of bone density, bone biomarkers, and indicators of physical function. Improving yogurt intakes could be a valuable health strategy for maintaining bone health in older adults., Introduction: The associations of yogurt intakes with bone health and frailty in older adults are not well documented. The aim was to investigate the association of yogurt intakes with bone mineral density (BMD), bone biomarkers, and physical function in 4310 Irish adults from the Trinity, Ulster, Department of Agriculture aging cohort study (TUDA)., Methods: Bone measures included total hip, femoral neck, and vertebral BMD with bone biochemical markers. Physical function measures included Timed Up and Go (TUG), Instrumental Activities of Daily Living Scale, and Physical Self-Maintenance Scale., Results: Total hip and femoral neck BMD in females were 3.1-3.9% higher among those with the highest yogurt intakes (n = 970) compared to the lowest (n = 1109; P < 0.05) as were the TUG scores (-6.7%; P = 0.013). In males, tartrate-resistant acid phosphatase (TRAP 5b) concentrations were significantly lower in those with the highest yogurt intakes (-9.5%; P < 0.0001). In females, yogurt intake was a significant positive predictor of BMD at all regions. Each unit increase in yogurt intake in females was associated with a 31% lower risk of osteopenia (OR 0.69; 95% CI 0.49-0.96; P = 0.032) and a 39% lower risk of osteoporosis (OR 0.61; 95% CI 0.42-0.89; P = 0.012) and in males, a 52% lower risk of osteoporosis (OR 0.48; 95% CI 0.24-0.96; P = 0.038)., Conclusion: In this cohort, higher yogurt intake was associated with increased BMD and physical function scores. These results suggest that improving yogurt intakes could be a valuable public health strategy for maintaining bone health in older adults.

Introduction: Neurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than α-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive., Objectives: To study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls., Methods: CSF was collected consecutively from 134 participants; Parkinson's disease (n = 26), atypical parkinsonian syndromes (n = 78, including progressive supranuclear palsy (n = 36), multiple system atrophy (n = 28), corticobasal syndrome (n = 14)), and elderly healthy controls (n = 30). Participants were divided into a discovery and a validation set for analysis. The samples were subjected to tryptic digestion, followed by liquid chromatography-mass spectrometry analysis for identification and relative quantification by isobaric labelling. Candidate protein biomarkers were identified based on the relative abundances of the identified tryptic peptides. Their predictive performance was evaluated by analysis of the validation set., Results: 79 tryptic peptides, derived from 26 proteins were found to differ significantly between atypical parkinsonism patients and controls. They included acute phase/inflammatory markers and neuronal/synaptic markers, which were respectively increased or decreased in atypical parkinsonism, while their levels in PD subjects were intermediate between controls and atypical parkinsonism., Conclusion: Using an unbiased proteomic approach, proteins were identified that were able to differentiate atypical parkinsonian syndrome patients from healthy controls. Our study indicates that markers that may reflect neuronal function and/or plasticity, such as the amyloid precursor protein, and inflammatory markers may hold future promise as candidate biomarkers in parkinsonism., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Consumption of dairy products has been associated with positive health outcomes including a lower risk of hypertension, improved bone health and a reduction in the risk of type 2 diabetes. The suggested dairy intake for health in older adults is three servings per day but recent analysis of the NHANES data for older adults reported 98% were not meeting these recommendations. No studies have investigated the consequences of such declines in the dairy intakes of Irish older adults and the subsequent effects on vitamin micronutrient status., Objectives: To study the daily dairy intakes of older Irish adults and to examine how the frequency of dairy food consumption affects vitamin micronutrient status., Methods: Participants (n 4,317) were from the Trinity Ulster Department of Agriculture (TUDA) Study, a large study of older Irish adults (aged >60 yrs) designed to investigate gene-nutrient interactions in the development of chronic diseases of aging. The daily intake portion for milk, cheese and yoghurt was calculated from food frequency questionnaire (FFQ) responses. Blood samples were analysed for vitamin biomarkers as follows: vitamin B12 (total serum cobalamin and holotranscobalamin (holoTC)), folate (red cell folate (RCF) and serum folate), vitamin B2 (erythrocyte glutathione reductase activation coefficient (EGRac)), vitamin B6 (serum pyridoxal phosphate) and vitamin D (serum 25(OH)D)., Results: The mean total reported dairy intake was 1.16 (SD 0.79) portions per day with males consuming significantly fewer total dairy portions compared to females (1.07 vs 1.21 respectively) (P<0.05). There was no significant difference in total daily dairy serving intakes by age decade (60-69, 70-79, >80 yrs). Overall, only 3.5% of the total population (n 151) achieved the recommended daily dairy intake of three or more servings per day. A significantly higher proportion of females (4%) compared to males (2.4%) met these dairy requirements (P=0.011). Blood concentrations of vitamin B12 biomarkers, RCF, vitamin B2 and vitamin B6 were significantly worse in those with the lowest tertile of dairy intake (0-0.71 servings) compared to those in the highest tertile (1.50-4.50 servings) (P<0.05)., Conclusion: This study found that more than 96% of the older adults sampled did not meet current daily dairy intake recommendations. The study is the largest to-date examining dairy intakes in older Irish adults, and provides evidence that daily dairy intakes (in particular yogurt) contribute significantly to the B-vitamin and vitamin D biomarker status of older adults. These results suggest that older adults who are already vulnerable to micronutrient inadequacies, are forgoing the nutritional advantages of vitamin-rich dairy products., Competing Interests: Dr. Laird reports grants from Irish Department of Agriculture, Food and the Marine, grants from The National Dairy Council (NDC) Ireland, during the conduct of the study. Dr. Casey has nothing to disclose. Dr. Ward has nothing to disclose. Dr. Hoey has nothing to disclose. Dr. Hughes has nothing to disclose. Dr. McCarroll has nothing to disclose. Dr. Cunningham has nothing to disclose. Dr. Strain has nothing to disclose. Dr. McNulty has nothing to disclose. Dr. Molloy has nothing to disclose.

Background: The Frontal Assessment Battery (FAB) is a short battery designed to assess frontal executive functioning, but data for interpretation of performance are limited., Objectives: The Trinity, Ulster, Department of Agriculture (TUDA) study provided the opportunity to derive performance data from a large sample of community-dwelling hospital outpatient or general practitioner (GP) attenders., Methods: Normative analysis based on 2508 TUDA participants meeting these criteria: Mini-Mental State Examination (MMSE) >26/30, not depressed (Center for Epidemiologic Studies Depression <16) or anxious (Hospital Anxiety and Depression Scale <8), no history of stroke, or transient ischemic attack. Correlation and regression analyses were used to evaluate the effects of age, education, gender, and general cognition (MMSE). Norms for FAB were created stratified by age and education, using overlapping midpoint ranges of 10 years with a 3-year interval from age 60 to 97., Results: Age and education accounted for 9.6% of variance in FAB score ( r 2 = .096) with no significant effect of gender. The FAB and MMSE were modestly correlated ( r = .29, P < .01) with MMSE increasing the model's total explained variance in FAB score from 9.6% to 14%., Conclusion: This is the largest study to date to create normative data for the FAB. Age and education had the most significant impact on FAB performance, which was largely independent of global cognition (MMSE). These data may be of benefit in interpreting FAB performance in individuals with similar demographic/health status characteristics in hospital outpatient or GP settings.

Cardiac tamponade is a rare complication of coronary intervention to chronic total occlusions (CTO PCI). We report a case of persistent bleeding from a venous source following successful anterograde dissection-reentry (ADR) CTO PCI. Pericardiocentesis was performed 1 h post-procedure for tamponade. Persistent bleeding was investigated with contrast transesophageal echocardiography, pericardial manometry and blood analysis. Coronary venography revealed subtle extravasation from a cardiac vein adjacent to the site of luminal re-entry. Coronary venous perforation using ADR CTO PCI has not previously been described; however, the volume of blood loss may be significant and surgical exploration may be appropriate.

Clinical deficiency of the B-vitamin riboflavin (vitamin B2) is largely confined to developing countries; however accumulating evidence indicates that suboptimal riboflavin status is a widespread problem across the developed world. Few international data are available on riboflavin status as measured by the functional biomarker, erythrocyte glutathione reductase activation coefficient, considered to be the gold standard index. One important role of riboflavin in the form of flavin dinucleotide is as a co-factor for the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR). Homozygosity for the common C677T polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide, has been associated with an increased risk of CVD, and more recently with hypertension. This review will explore available studies reporting riboflavin status worldwide, the interaction of riboflavin with the MTHFR C677T polymorphism and the potential role of riboflavin in personalised nutrition. Evidence is accumulating for a novel role of riboflavin as an important modulator of blood pressure (BP) specifically in individuals with the MTHFR 677TT genotype, with results from a number of recent randomised controlled trials demonstrating that riboflavin supplementation can significantly reduce systolic BP by 5-13 mmHg in these genetically at risk adults. Studies are however required to investigate the BP-lowering effect of riboflavin in different populations and in response to doses higher than 1·6 mg/d. Furthermore, work focusing on the translation of this research to health professionals and patients is also required.

Background: Thrombolysis can significantly reduce the burden of stroke but the time window for safe and effective treatment is short. In patients travelling to hospital via ambulance, the sending of a 'prealert' message can significantly improve the timeliness of treatment., Objective: Examine the prevalence of hospital prealerting, the extent to which prealert protocols are followed and what factors influence emergency medical services (EMS) staff's decision to send a prealert., Methods: Cohort study of patients admitted to two acute stroke units in West Midlands (UK) hospitals using linked data from hospital and EMS records. A logistic regression model examined the association between prealert eligibility and whether a prealert message was sent. In semistructured interviews, EMS staff were asked about their experiences of patients with suspected stroke., Results: Of the 539 patients eligible for this study, 271 (51%) were recruited. Of these, only 79 (29%) were eligible for prealerting according to criteria set out in local protocols but 143 (53%) were prealerted. Increasing number of Face, Arm, Speech Test symptoms (1 symptom, OR 6.14, 95% CI 2.06 to 18.30, p=0.001; 2 symptoms, OR 31.36, 95% CI 9.91 to 99.24, p<0.001; 3 symptoms, OR 75.84, 95% CI 24.68 to 233.03, p<0.001) and EMS contact within 5 h of symptom onset (OR 2.99, 95% CI 1.37 to 6.50 p=0.006) were key predictors of prealerting but eligibility for prealert as a whole was not (OR 1.92, 95% CI 0.85 to 4.34 p=0.12). In qualitative interviews, EMS staff displayed varying understanding of prealert protocols and described frustration when their interpretation of the prealert criteria was not shared by ED staff., Conclusions: Up to half of the patients presenting with suspected stroke in this study were prealerted by EMS staff, regardless of eligibility, resulting in disagreements with ED staff during handover. Aligning the expectations of EMS and ED staff, perhaps through simplified prealert protocols, could be considered to facilitate more appropriate use of hospital prealerting in acute stroke., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease. The major pathological hallmark of MSA is the accumulation of α-synuclein in oligodendrocytes. In contrast to Parkinson's disease no definitive familial etiology for MSA has been determined. Yet, there is a growing body of evidence that perturbation of transcriptional processes leads to MSA pathology. Here we present the results of the first ribosomal-depleted strand-specific RNA-sequencing profile of the MSA brain frontal cortex tissue. Among the 123 differentially expressed genes over 50% were categorized as putative long intervening non-coding RNAs (lincRNAs). Along with the dysregulation of the non-coding portion of the transcriptome, the expression of protein coding genes was also affected, including serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 (SERPINA3), interleukin 1 receptor-like 1 (IL1RL1) and hemoglobin, beta (HBB). Also of interest was the alternative splicing of SNCA, along with the presence of an antisense transcript overlapping the 3' exon of SNCA. Moreover, we demonstrate widespread antisense transcription throughout the frontal cortex that is largely not affected by MSA-specific neurodegenerative process. MSA causes a large disruption of lincRNAs in the human brain along with protein coding genes related to iron metabolism and immune response regulation. Most of the lincRNAs specific for MSA were novel. Hence our study uncovers another level of complexity in transcriptional pathology of MSA., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: To evaluate the ability of community-based exercise programmes to facilitate public participation in exercise and hence improved cardiovascular health, we assessed the respective impacts of: a continuously monitored exercise programme based within our university (study 1); a Valleys Regional Park-facilitated community-based outdoor exercise programme (study 2); a Wales National Exercise Referral Scheme-delivered exercise-referral programme (study 3)., Methods: Biomolecular (monocytic PPARγ target gene expression), vascular haemodynamic (central/peripheral blood pressure, arterial stiffness), clinical (insulin sensitivity, blood lipids) and anthropometric (body mass index, waist circumference, heart rate) parameters were investigated using RT-PCR, applanation tonometry, chemical analysis and standard anthropometric techniques., Results: In studies 1-3, 22/28, 32/65 and 11/14 participants adhered to their respective exercise programmes, and underwent significant increases in physical activity levels. Importantly, beneficial effects similar to those seen in our previous studies (eg, modulations in expression of monocytic PPARγ target genes, decreases in blood pressure/arterial stiffness, improvements in blood lipids/insulin sensitivity) were observed (albeit to slightly differing extents) only in participants who adhered to their respective exercise programmes. While study 1 achieved more intense exercise and more pronounced beneficial effects, significant cardiovascular risk-lowering health benefits related to biomolecular markers, blood pressure, arterial stiffness and blood lipids were achieved via community/referral-based delivery modes in studies 2 and 3., Conclusions: Because cardiovascular health benefits were observed in all 3 studies, we conclude that the majority of benefits previously reported in laboratory-based studies can also be achieved in community-based/exercise-referral settings. These findings may be of use in guiding policymakers with regard to introduction and/or continued implementation of community/referral-based exercise programmes.

We believe this is the first study to investigate associations between blood metabolites and neocortical amyloid burden (NAB) in the search for a blood-based biomarker for Alzheimer's disease (AD). Further, we present the first multi-modal analysis of blood markers in this field. We used blood plasma samples from 91 subjects enrolled in the University of California, San Francisco Alzheimer's Disease Research Centre. Non-targeted metabolomic analysis was used to look for associations with NAB using both single and multiple metabolic feature models. Five metabolic features identified subjects with high NAB, with 72% accuracy. We were able to putatively identify four metabolites from this panel and improve the model further by adding fibrinogen gamma chain protein measures (accuracy=79%). One of the five metabolic features was studied in the Alzheimer's Disease Neuroimaging Initiative cohort, but results were inconclusive. If replicated in larger, independent studies, these metabolic features and proteins could form the basis of a blood test with potential for enrichment of amyloid pathology in anti-amyloid trials.

The International Agency for Research on Cancer recognises five viruses, one bacterium and three parasites as having a causal relationship to cancer, and one virus, HIV, that by suppressing the immune system assists in the development of cancer. In addition numerous researchers have claimed links between cancer and other viruses and bacteria, many of which have been isolated from tumours. Excluding the non-causal HIV, 33 infectious agents linked with cancer have been identified in the literature, 27 of which have one thing in common: they are all present in mosquitoes. There are over 3000 species of mosquito and very few have been fully analysed, so the six remaining infectious agents may be present in some unexamined species. This hypothesis proposes that more cancers than are presently appreciated may arise from the long-term outcome of a mosquito bite, which by releasing a complex cocktail of up to 60 infectious agents directly into the blood stream, often results in contemporaneous immuno-suppression and a multiplicity of co-infections. These co-infections may act synergistically in whole, or in part, and in complex ways. Whether and if so which type of cancer ensues will depend on the constituent ingredients in the cocktail, determined by multiple factors such as the mosquito's drinking and feeding patterns, number of previous blood-meals and the variety of intermediate hosts from which these meals are taken. Only a few mosquito species carry malaria, dengue fever, chikungunya and the other recognised serious human ailments. This hypothesis suggests that the number of species carrying the cancer cocktail will be few in number but collectively have a worldwide presence., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The purpose of this study was to evaluate the microbial community (MC) composition as it relates to salivary metabolites and periodontal clinical parameters in a 21-d biofilm-overgrowth model. Subjects (N = 168) were enrolled equally into 5 categories of periodontal status per the biofilm-gingival interface classification. Microbial species within subgingival plaque samples were identified by human microbiome identification microarray. Whole saliva was analyzed by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry for metabolite identification. Phylum was grouped into MCs according to principal component analysis. Generalized linear and regression models were used to examine the association among MC, species, periodontal clinical parameters, and salivary metabolome. Multiple comparisons were adjusted with the false discovery rate. The study population was distributed into 8 distinct MC profiles, designated MC-1 to MC-8. MC-2 explained 14% of the variance and was dominated by Synergistetes and Spirochaetes. It was the only community structure significantly associated with high probing depth (P = 0.02) and high bleeding on probing (P = 0.008). MC-2 was correlated with traditional periodontal pathogens and several newly identified putative periodontal pathogens: Fretibacterium fastidiosum, Fretibacterium sp. OT360/OT362, Filifactor alocis, Treponema lecithinolyticum, Eubacterium saphenum, Desulfobulbus sp./OT041, and Mogibacterium timidum. Synergistetes phylum was strongly associated with 2 novel metabolites-cyclo (-leu-pro) and cyclo (-phe-pro)-at 21 d of biofilm overgrowth (P = 0.02). In subjects with severe periodontitis (P2 and P3), cyclo (-leu-pro) and cyclo (-phe-pro) were significantly associated with increased changes in probing depth at 21 d of biofilm overgrowth (P ≤ 0.05). The analysis identified a MC dominated by Synergistetes, with classic and putative newly identified pathogens/pathobionts associated with clinical disease. The metabolomic discovery of 2 novel cyclodipeptides that have been reported to serve as quorum-sensing and/or bacteriocidal/bacteriostatic molecules, in association with Synergistetes, suggests a potential role in periodontal biofilm dysbiosis and periodontal disease that warrants further investigation., (© International & American Associations for Dental Research 2015.)