Dimethylsulfide (DMS) production in polar oceans is resilient to ocean acidification

Emissions of dimethylsulfide (DMS) from the polar oceans play a key role in atmospheric processes and climate. Therefore, it is important we increase our understanding of how DMS production in these regions may respond to environmental change. The polar oceans are particularly vulnerable to ocean acidification (OA). However, our understanding of the polar DMS response is limited to two studies conducted in Arctic waters, where in both cases DMS concentrations decreased with increasing acidity. Here, we report on our findings from seven summertime shipboard microcosm experiments undertaken in a variety of locations in the Arctic Ocean and Southern Ocean. These experiments reveal no significant effects of short term OA on the net production of DMS by planktonic communities. This is in contrast to identical experiments from temperate NW European shelf waters where surface ocean communities responded to OA with significant increases in dissolved DMS concentrations. A meta-analysis of the findings from both temperate and polar waters (n=18 experiments) reveals clear regional differences in the DMS response to OA. We suggest that these regional differences in DMS response reflect the natural variability in carbonate chemistry to which the respective communities may already be adapted. Future temperate oceans could be more sensitive to OA resulting in a change in DMS emissions to the atmosphere, whilst perhaps surprisingly DMS emissions from the polar oceans may remain relatively unchanged. By demonstrating that DMS emissions from geographically distinct regions may vary in response to OA, our results may facilitate a better understanding of Earth's future climate. Our study suggests that the way in which processes that generate DMS respond to OA may be regionally distinct and this should be taken into account in predicting future DMS emissions and their influence on Earth's climate

Cross Sectional Associations between Socio-Demographic Factors and Cognitive Performance in an Older British Population: The European Investigation of Cancer in Norfolk (EPIC-Norfolk) Study

$\textbf{BACKGROUND}$: Cognition covers a range of abilities, such as memory, response time and language, with tests assessing either specific or generic aspects. However differences between measures may be observed within the same individuals. $\textbf{OBJECTIVE}$: To investigate the cross-sectional association of cognitive performance and socio-demographic factors using different assessment tools across a range of abilities in a British cohort study. $\textbf{METHODS}$: Participants of the European Prospective Investigation of Cancer (EPIC) in Norfolk Study, aged 48-92 years, underwent a cognitive assessment between 2006 and 2011 (piloted between 2004 and 2006) and were investigated over a different domains using a range of cognitive tests. $\textbf{RESULTS}$: Cognitive measures were available on 8584 men and women. Though age, sex, education and social class were all independently associated with cognitive performance in multivariable analysis, different associations were observed for different cognitive tests. Increasing age was associated with increased risk of a poor performance score in all of the tests, except for the National Adult Reading Test (NART), an assessment of crystallized intelligence. Compared to women, men were more likely to have had poor performance for verbal episodic memory, Odds Ratio, OR = 1.99 (95% Confidence Interval, 95% CI 1.72, 2.31), attention OR = 1.62, (95% CI 1.39, 1.88) and prospective memory OR = 1.46, (95% CI 1.29, 1.64); however, no sex difference was observed for global cognition, OR = 1.07 (95%CI 0.93, 1.24). The association with education was strongest for NART, and weakest for processing speed. $\textbf{CONCLUSION}$: Age, sex, education and social class were all independently associated with performance on cognitive tests assessing a range of different domains. However, the magnitude of associations of these factors with different cognitive tests differed. The varying relationships seen across different tests may help explain discrepancies in results reported in the current literature, and provides insights into influences on cognitive performance in later life.The infrastructure for this study was supported by the Medical Research Council, UK http://www.mrc.ac.uk/ (Ref: G0401527) and Cancer Research UK http://www.cancerresearchuk.org/ (CRUK, Ref: C864/A8257). The clinic for EPIC-Norfolk 3 was funded by Research into Ageing, now known as Age UK http://www.ageuk.org.uk/ (Grant Ref: 262). The pilot phase was supported by MRC (Ref: G9502233) and CRUK (Ref: C864/A2883). KK received the above funding. FEM Is supported by MRC (Ref: U105292687)

Relationships of brain cholesterol and cholesterol biosynthetic enzymes to Alzheimer’s pathology and dementia in the CFAS population-derived neuropathology cohort

Altered cholesterol metabolism is implicated in brain ageing and Alzheimer’s disease. We examined whether key genes regulating cholesterol metabolism and levels of brain cholesterol are altered in dementia and Alzheimer’s disease neuropathological change (ADNC). Temporal cortex (n = 99) was obtained from the Cognitive Function and Ageing Study. Expression of the cholesterol biosynthesis rate-limiting enzyme HMG-CoA reductase (HMGCR) and its regulator, SREBP2, were detected using immunohistochemistry. Expression of HMGCR, SREBP2, CYP46A1 and ABCA1 were quantified by qPCR in samples enriched for astrocyte and neuronal RNA following laser-capture microdissection. Total cortical cholesterol was measured using the Amplex Red assay. HMGCR and SREBP2 proteins were predominantly expressed in pyramidal neurones, and in glia. Neuronal HMGCR did not vary with ADNC, oxidative stress, neuroinflammation or dementia status. Expression of HMGCR neuronal mRNA decreased with ADNC (p = 0.022) and increased with neuronal DNA damage (p = 0.049), whilst SREBP2 increased with ADNC (p = 0.005). High or moderate tertiles for cholesterol levels were associated with increased dementia risk (OR 1.44, 1.58). APOE ε4 allele was not associated with cortical cholesterol levels. ADNC is associated with gene expression changes that may impair cholesterol biosynthesis in neurones but not astrocytes, whilst levels of cortical cholesterol show a weak relationship to dementia status

Association of Aortic Stiffness With Biomarkers of Neuroinflammation, Synaptic Dysfunction, and Neurodegeneration

OBJECTIVES: To test the hypothesis that increased aortic stiffening is associated with greater cerebrospinal fluid (CSF) evidence of core Alzheimer's disease pathology (Aβ, phosphorylated tau (p-tau)), neurodegeneration (total tau (t-tau)), synaptic dysfunction (neurogranin), neuroaxonal injury (neurofilament light (NFL)), and neuroinflammation (YKL-40, sTREM2), we analyzed pulse wave velocity (PWV) data and CSF data among older adults. METHODS: Participants free of stroke and dementia from the Vanderbilt Memory and Aging Project, an observational community-based study, underwent cardiac magnetic resonance to assess aortic pulse wave velocity (PWV, m/sec) and lumbar puncture to obtain CSF. Linear regressions related aortic PWV to CSF Aβ, p-tau, t-tau, neurogranin, NFL, YKL-40, and sTREM2 concentrations adjusting for age, race/ethnicity, education, apolipoprotein (APOE) ε4 status, Framingham Stroke Risk Profile, and cognitive diagnosis. Models were repeated testing PWV interactions with age, diagnosis, APOE-ε4, and hypertension on each biomarker. RESULTS: 146 participants were examined (72±6 years). Aortic PWV interacted with age on p-tau (β=0.31, p=0.04), t-tau, (β=2.67, p=0.05), neurogranin (β=0.94, p=0.04), and sTREM2 (β=20.4, p=0.05). Among participants over age 73 years, higher aortic PWV related to higher p-tau (β=2.4, p=0.03), t-tau (β=19.3, p=0.05), neurogranin (β=8.4, p=0.01), and YKL-40 concentrations (β=7880, p=0.005). Aortic PWV had modest interactions with diagnosis on neurogranin (β=-10.76, p=0.03) and hypertension status on YKL-40 (β=-18020, p<0.001). CONCLUSIONS: Among our oldest participants, age 74 years and older, greater aortic stiffening is associated with in vivo biomarker evidence of neuroinflammation, tau phosphorylation, synaptic dysfunction, and neurodegeneration, but not amyloidosis. Central arterial stiffening may lead to cumulative cerebral microcirculatory damage and blood flow delivery to tissue, resulting in neuroinflammation and neurodegeneration in more advanced age

Focused Deterrence and the Prevention of Violent Gun Injuries: Practice, Theoretical Principles, and Scientific Evidence

Focused deterrence strategies are a relatively new addition to a growing portfolio of evidence-based violent gun injury prevention practices available to policy makers and practitioners. These strategies seek to change offender behavior by understanding the underlying violence-producing dynamics and conditions that sustain recurring violent gun injury problems and by implementing a blended strategy of law enforcement, community mobilization, and social service actions. Consistent with documented public health practice, the focused deterrence approach identifies underlying risk factors and causes of recurring violent gun injury problems, develops tailored responses to these underlying conditions, and measures the impact of implemented interventions. This article reviews the practice, theoretical principles, and evaluation evidence on focused deterrence strategies. Although more rigorous randomized studies are needed, the available empirical evidence suggests that these strategies generate noteworthy gun violence reduction impacts and should be part of a broader portfolio of violence prevention strategies available to policy makers and practitioners

Early and Middle Holocene Hunter-Gatherer Occupations in Western Amazonia: The Hidden Shell Middens

We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region's past and offers a new context within which the late Holocene "Earthmovers" of the Llanos de Moxos could have emerged. © 2013 Lombardo et al

Using Human Disease Outbreaks as a Guide to Multilevel Ecosystem Interventions

Human health often depends on environmental variables and is generally subject to widespread and comprehensive surveillance. Compared with other available measures of ecosystem health, human disease incidence may be one of the most useful and practical bioindicators for the often elusive gauge of ecologic well-being. We argue that many subtle ecosystem disruptions are often identified only as a result of detailed epidemiologic investigations after an anomalous increase in human disease incidence detected by routine surveillance mechanisms. Incidence rates for vector-mediated diseases (e.g., arboviral illnesses) and direct zoonoses (e.g., hantaviruses) are particularly appropriate as bioindicators to identify underlying ecosystem disturbances. Outbreak data not only have the potential to act as a pivotal warning system for ecosystem disruption, but may also be used to identify interventions for the preservation of ecologic health. With this approach, appropriate ecologically based strategies for remediation can be introduced at an earlier stage than would be possible based solely on environmental monitoring, thereby reducing the level of “ecosystem distress” as well as resultant disease burden in humans. This concept is discussed using local, regional, and global examples, thereby introducing the concept of multilevel ecosystem interventions

Cross Sectional Associations between Socio-Demographic Factors and Cognitive Performance in an Older British Population: The European Investigation of Cancer in Norfolk (EPIC-Norfolk) Study.

BACKGROUND: Cognition covers a range of abilities, such as memory, response time and language, with tests assessing either specific or generic aspects. However differences between measures may be observed within the same individuals. OBJECTIVE: To investigate the cross-sectional association of cognitive performance and socio-demographic factors using different assessment tools across a range of abilities in a British cohort study. METHODS: Participants of the European Prospective Investigation of Cancer (EPIC) in Norfolk Study, aged 48-92 years, underwent a cognitive assessment between 2006 and 2011 (piloted between 2004 and 2006) and were investigated over a different domains using a range of cognitive tests. RESULTS: Cognitive measures were available on 8584 men and women. Though age, sex, education and social class were all independently associated with cognitive performance in multivariable analysis, different associations were observed for different cognitive tests. Increasing age was associated with increased risk of a poor performance score in all of the tests, except for the National Adult Reading Test (NART), an assessment of crystallized intelligence. Compared to women, men were more likely to have had poor performance for verbal episodic memory, Odds Ratio, OR = 1.99 (95% Confidence Interval, 95% CI 1.72, 2.31), attention OR = 1.62, (95% CI 1.39, 1.88) and prospective memory OR = 1.46, (95% CI 1.29, 1.64); however, no sex difference was observed for global cognition, OR = 1.07 (95%CI 0.93, 1.24). The association with education was strongest for NART, and weakest for processing speed. CONCLUSION: Age, sex, education and social class were all independently associated with performance on cognitive tests assessing a range of different domains. However, the magnitude of associations of these factors with different cognitive tests differed. The varying relationships seen across different tests may help explain discrepancies in results reported in the current literature, and provides insights into influences on cognitive performance in later life.The infrastructure for this study was supported by the Medical Research Council, UK http://www.mrc.ac.uk/ (Ref: G0401527) and Cancer Research UK http://www.cancerresearchuk.org/ (CRUK, Ref: C864/A8257). The clinic for EPIC-Norfolk 3 was funded by Research into Ageing, now known as Age UK http://www.ageuk.org.uk/ (Grant Ref: 262). The pilot phase was supported by MRC (Ref: G9502233) and CRUK (Ref: C864/A2883). KK received the above funding. FEM Is supported by MRC (Ref: U105292687)

Is it feasible to deliver a complex intervention to improve the outcome of falls in people with dementia? A protocol for the DIFRID feasibility study

Background: People with dementia (PWD) experience ten times as many incident falls as people without dementia. Little is known about how best to deliver services to people with dementia following a fall. We used an integrated, mixed-methods approach to develop a new intervention which combines theory generated via a realist synthesis and data on current provision and pathways, gathered through a prospective observational study as well as qualitative interviews, focus groups, and ethnographic observation. This intervention is to be tested in a feasibility study in the UK National Health Service. Methods: People living with dementia in one of three geographical areas will be eligible for the study if they experience a fall requiring healthcare attention and have an informal carer. Potential participants will be identified by community services (primary care, paramedics, telecare), secondary care (ED; facilitated discharge services; rehabilitation outreach teams) and research case registers. Participants will receive a complex multidisciplinary intervention focused on their goals and interests for up to 12 weeks. The intervention will be delivered by occupational therapists, physiotherapists and rehabilitation support workers. Feasibility outcomes will include recruitment and retention, suitability and acceptability of outcome measures and acceptability, feasibility and fidelity of intervention components. PWD outcome measures will include number of falls, Montreal Cognitive Assessment (MOCA), European Quality of Life Instrument (EQ-5D-5L), Quality of Life–Alzheimer’s Disease Scale (QOL-AD), Modified Falls Efficacy Scale (MFES) and Goal Attainment Scaling (GAS). PWD outcome measures completed by an informal carer will include Disability Assessment for Dementia (DAD), EQ-5D-5L Proxy, QoL-AD Proxy and a Health Utilisation Questionnaire (HUQ), The carer outcome measure will be the Zarit Burden Interview (ZBI). An embedded process evaluation will explore barriers and facilitators to recruitment and intervention delivery. Discussion: The study results will inform whether and how a larger multicentre RCT should be undertaken. A full RCT would have the potential to show how outcomes can be improved for people with dementia who have fallen. Ethics and dissemination: The National Research Ethics Service Committee Newcastle and North Tyneside 2 approved the feasibility study. Trial registration: International Standard Randomised Controlled Trial Registry Registration number: ISRCTN41760734 Date of registration: 16/11/201