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26.  A continent-wide analysis of the shade requirements of red and western grey kangaroos 
Foraging time may be constrained by a suite of phenomena including weather, which can restrict a species' activity and energy intake. This is recognized as pivotal for many species whose distributions are known to correlate with climate, including kangaroos, although such impacts are rarely quantified. We explore how differences in shade seeking, a thermoregulatory behavior, of 2 closely-related kangaroo species, Macropus rufus (red kangaroos) and M. fuliginosus (western grey kangaroos), might reflect differences in their distributions across Australia. We observed foraging and shade-seeking behavior in the field and, together with local weather observations, calculated threshold radiant temperatures (based on solar and infrared radiant heat loads) over which the kangaroos retreated to shade. We apply these calculated tolerance thresholds to hourly microclimatic estimates derived from daily-gridded weather data to predict activity constraints across the Australian continent over a 10-year period. M. fuliginosus spent more time than M. rufus in the shade (7.6 ± 0.7 h versus 6.4 ± 0.9 h) and more time foraging (11.8 ± 0.5 h vs. 10.0 ± 0.6 h), although total time resting was equivalent (∼8.2 h). M. rufus tolerated 19°C higher radiant temperatures than M. fuliginosus (89°C versus 70°C radiant temperature). Across Australia, we predicted M. fuliginosus to be more restricted to shade than M. rufus, with higher absolute shade requirements farther north. These results corroborate previous findings that M. rufus is more adept at dealing with heat than M. fuliginosus and indicate that M. rufus is less dependent on shade on a continental scale.
PMCID: PMC4965007  PMID: 27857963
activity budget; endotherm; time budget; marsupial; range limits; shade-seeking behavior; thermoregulation; temperature tolerance
28.  How Can Psychological Science Inform Research About Genetic Counseling for Clinical Genomic Sequencing? 
Journal of genetic counseling  2014;24(2):193-204.
Next generation genomic sequencing technologies (including whole genome or whole exome sequencing) are being increasingly applied to clinical care. Yet, the breadth and complexity of sequencing information raise questions about how best to communicate and return sequencing information to patients and families in ways that facilitate comprehension and optimal health decisions. Obtaining answers to such questions will require multidisciplinary research. In this paper, we focus on how psychological science research can address questions related to clinical genomic sequencing by explaining emotional, cognitive, and behavioral processes in response to different types of genomic sequencing information (e.g., diagnostic results and incidental findings). We highlight examples of psychological science that can be applied to genetic counseling research to inform the following questions: (1) What factors influence patients' and providers' informational needs for developing an accurate understanding of what genomic sequencing results do and do not mean?; (2) How and by whom should genomic sequencing results be communicated to patients and their family members?; and (3) How do patients and their families respond to uncertainties related to genomic information?
PMCID: PMC4777349  PMID: 25488723
Communication; Genome sequencing; Patient understanding; Psychological; Psychosocial
29.  11β-hydroxysteroid dehydrogenase inhibition as a new potential therapeutic target for alcohol abuse 
Translational Psychiatry  2016;6(3):e760-.
The identification of new and more effective treatments for alcohol abuse remains a priority. Alcohol intake activates glucocorticoids, which have a key role in alcohol's reinforcing properties. Glucocorticoid effects are modulated in part by the activity of 11β-hydroxysteroid dehydrogenases (11β-HSD) acting as pre-receptors. Here, we tested the effects on alcohol intake of the 11β-HSD inhibitor carbenoxolone (CBX, 18β-glycyrrhetinic acid 3β-O-hemisuccinate), which has been extensively used in the clinic for the treatment of gastritis and peptic ulcer and is active on both 11β-HSD1 and 11β-HSD2 isoforms. We observed that CBX reduces both baseline and excessive drinking in rats and mice. The CBX diastereomer 18α-glycyrrhetinic acid 3β-O-hemisuccinate (αCBX), which we found to be selective for 11β-HSD2, was also effective in reducing alcohol drinking in mice. Thus, 11β-HSD inhibitors may be a promising new class of candidate alcohol abuse medications, and existing 11β-HSD inhibitor drugs may be potentially re-purposed for alcohol abuse treatment.
PMCID: PMC4872439  PMID: 26978742
30.  Physiological response of the cold-water coral Desmophyllum dianthus to thermal stress and ocean acidification 
PeerJ  2016;4:e1606.
Rising temperatures and ocean acidification driven by anthropogenic carbon emissions threaten both tropical and temperate corals. However, the synergistic effect of these stressors on coral physiology is still poorly understood, in particular for cold-water corals. This study assessed changes in key physiological parameters (calcification, respiration and ammonium excretion) of the widespread cold-water coral Desmophyllum dianthus maintained for ∼8 months at two temperatures (ambient 12 °C and elevated 15 °C) and two pCO2 conditions (ambient 390 ppm and elevated 750 ppm). At ambient temperatures no change in instantaneous calcification, respiration or ammonium excretion rates was observed at either pCO2 levels. Conversely, elevated temperature (15 °C) significantly reduced calcification rates, and combined elevated temperature and pCO2 significantly reduced respiration rates. Changes in the ratio of respired oxygen to excreted nitrogen (O:N), which provides information on the main sources of energy being metabolized, indicated a shift from mixed use of protein and carbohydrate/lipid as metabolic substrates under control conditions, to less efficient protein-dominated catabolism under both stressors. Overall, this study shows that the physiology of D. dianthus is more sensitive to thermal than pCO2 stress, and that the predicted combination of rising temperatures and ocean acidification in the coming decades may severely impact this cold-water coral species.
PMCID: PMC4741066  PMID: 26855864
Cold-water corals; Thermal stress; Ocean acidification; Coral calcification; Coral respiration; Coral excretion
31.  Factors Affecting Recall of Different Types of Personal Genetic Information about Alzheimer's Disease Risk: The REVEAL Study 
Public health genomics  2015;18(2):78-86.
Risk communication and assuring comprehension of risk information are essential components of providing persons with personalized genetic risk information. One measure that is commonly used to assess the efficacy of risk communication is risk recall. Our primary aim was to examine whether particular types of genetic risk information are especially challenging for some people to recall.
Data were obtained through a multi-site clinical trial in which different types of genetic risk-related information were disclosed to individuals (n=246) seeking a risk assessment for Alzheimer's disease.
Six weeks after disclosure, 83% of participants correctly recalled the number of risk-increasing APOE alleles they possessed, and 74% correctly recalled their APOE genotype. While 84% of participants recalled their lifetime risk estimate to within five percentage points, only 51% correctly recalled their lifetime risk estimate exactly. Correct recall of the number of APOE risk-increasing alleles was independently associated with higher education (p<0.001), greater numeracy (p<0.05) and stronger family history of Alzheimer's disease (p<0.05). Before adjustments for confounding, correct recall of APOE genotype was also associated with higher education, greater numeracy and stronger family history of Alzheimer's disease, as well as with higher comfort with numbers, and European American ethnicity (all p<0.05). Correct recall of the lifetime risk estimate was independently associated only with younger age (p<0.05).
Recall of genotype-specific information is high, but recall of exact risk estimates is lower. Incorrect recall of numeric risk may lead to distortions in understanding risk. Further research is needed to determine how best to communicate different types of genetic risk information to patients, particularly those with lower educational levels and lower numeracy. Healthcare professionals should be aware that each type of genetic risk information may be differentially interpreted and retained by patients, and that some patient subgroups may have more problems with recall than others.
PMCID: PMC4470386  PMID: 25634646
Risk recall; genetic testing; complex diseases; genetic counseling; risk assessment
32.  Outcome following Resection of Biliary Cystadenoma: A Single Centre Experience and Literature Review 
Background. Biliary cystadenomas (BCAs) are rare, benign, potentially malignant cystic lesions of the liver, accounting for less than 5% of cystic liver tumours. We report the outcome following resection of biliary cystadenoma from a single tertiary centre. Methods. Data of patients who had resection of BCA between January 1993 and July 2014 were obtained from liver surgical database. Patient demographics, clinicopathological characteristics, operative data, and postoperative outcome were analysed. Results. 29 patients had surgery for BCA. Male : female ratio was 1 : 28. Clinical presentation was abdominal pain (74%), jaundice (20%), abdominal mass (14%), and deranged liver function tests (3%). Cyst characteristics included septations (48%), wall thickening (31%), wall irregularity (38%), papillary projections (10%), and mural nodule (3%). Surgical procedures included atypical liver resection (52%), left hemihepatectomy (34%), right hemihepatectomy (10%), and left lateral segmentectomy (3%). Median length of stay was 7 (IQ 6.5–8.5) days. Two patients developed postoperative bile leak. No patients had malignancy on final histology. Median follow-up was 13 (IQ 6.5–15.7) years. One patient developed delayed biliary stricture and one died of cholangiocarcinoma 11 years later. Conclusion. Biliary cystadenomas can be resected safely with significantly low morbidity. Malignant transformation and recurrence are rare. Complete surgical resection provides a cure.
PMCID: PMC4709616  PMID: 26839708
33.  Crystal structure of bis­(1,3-di­amino­propane-κ2 N,N′)bis­[2-(4-nitro­phen­yl)acetato-κO]zinc(II) 
In the structure of the title compound, [Zn(C8H6NO4)2(C3H10N2)2], the ZnII atom is located on a center of symmetry with one independent Zn—O distance of 2.199 (2) Å, and two Zn—N distances of 2.157 (2) and 2.144 (2) Å. The overall coordination geometry around the ZnII atom is octa­hedral. Several types of hydrogen-bonding inter­actions are evident. Both intra­molecular [2.959 (3) Å] and inter­molecular [3.118 (3) and 3.124 (3) Å inter­actions occur between the O atoms of the acetate group and the amino N atoms, and weak inter­molecular C—H—O inter­actions involving the nitro groups, leading to an extended chain of the molecules aligned along the ac plane.
PMCID: PMC4719853  PMID: 26870444
crystal structure; zinc complex; coordination
34.  Using Quantum Confinement to Uniquely Identify Devices 
Scientific Reports  2015;5:16456.
Modern technology unintentionally provides resources that enable the trust of everyday interactions to be undermined. Some authentication schemes address this issue using devices that give a unique output in response to a challenge. These signatures are generated by hard-to-predict physical responses derived from structural characteristics, which lend themselves to two different architectures, known as unique objects (UNOs) and physically unclonable functions (PUFs). The classical design of UNOs and PUFs limits their size and, in some cases, their security. Here we show that quantum confinement lends itself to the provision of unique identities at the nanoscale, by using fluctuations in tunnelling measurements through quantum wells in resonant tunnelling diodes (RTDs). This provides an uncomplicated measurement of identity without conventional resource limitations whilst providing robust security. The confined energy levels are highly sensitive to the specific nanostructure within each RTD, resulting in a distinct tunnelling spectrum for every device, as they contain a unique and unpredictable structure that is presently impossible to clone. This new class of authentication device operates with minimal resources in simple electronic structures above room temperature.
PMCID: PMC4639737  PMID: 26553435
35.  The impact of direct-to-consumer personal genomic testing on perceived risk of breast, prostate, colorectal, and lung cancer: findings from the PGen study 
BMC Medical Genomics  2015;8:63.
Direct access to genomic information has the potential to transform cancer risk counseling. We measured the impact of direct-to-consumer genomic risk information on changes to perceived risk (ΔPR) of breast, prostate, colorectal and lung cancer among personal genomic testing (PGT) customers. We hypothesized that ΔPR would reflect directionality of risk estimates, attenuate with time, and be modified by participant characteristics.
Pathway Genomics and 23andMe customers were surveyed prior to receiving PGT results, and 2 weeks and 6 months post-results. For each cancer, PR was measured on a 5-point ordinal scale from “much lower than average” to “much higher than average.” PGT results, based on genotyping of common genetic variants, were dichotomized as elevated or average risk. The relationship between risk estimate and ΔPR was evaluated with linear regression; generalized estimating equations modeled this relationship over time.
With the exception of lung cancer (for which ΔPR was positive regardless of result), elevated risk results were significantly associated with positive ΔPR, and average risk results with negative ΔPR (e.g., prostate cancer, 2 weeks: least squares-adjusted ΔPR = 0.77 for elevated risk versus −0.21 for average risk; p-valuedifference < 0.0001) among 1154 participants. Large changes were rare: for each cancer, <4 % of participants overall reported a ΔPR of ±3 or more units. Effect modification by age, cancer family history, and baseline interest was observed for breast, colorectal, and lung cancer, respectively. A pattern of decreasing impact on ΔPR over time was consistently observed, but this trend was significant only in the case of colorectal cancer.
We have quantified the effect on consumer risk perception of returning genetic-based cancer risk information directly to consumers without clinician mediation. Provided via PGT, this information has a measurable but modest effect on perceived cancer risk, and one that is in some cases modified by consumers’ non-genetic risk context. Our observations of modest marginal effect sizes, infrequent extreme changes in perceived risk, and a pattern of diminishing impact with time, suggest that the ability of PGT to effect changes to cancer screening and prevention behaviors may be limited by relatively small changes to perceived risk.
Electronic supplementary material
The online version of this article (doi:10.1186/s12920-015-0140-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4606558  PMID: 26468061
36.  Public beliefs and knowledge about risk and protective factors for Alzheimer's disease 
The purpose of this study was to assess public beliefs and knowledge about risk and protective factors for Alzheimer's disease (AD).
A brief survey module was added to the Health and Retirement Study, a longstanding national panel study of the U.S. population over the age of 50.
Respondents were 1641 adults (mean age = 64.4 years, 53.6% female, 81.7% White). Most (60.1%) indicated interest in learning their AD risk, with 29.4% expressing active worry. Many failed to recognize that medications to prevent AD are not available (39.1%) or that having an affected first-degree relative is associated with increased disease risk (32%). Many respondents believed that various actions (e.g., mental activity, eating a healthy diet) would be effective in reducing AD risk.
Older and middle-aged adults are interested in their AD risk status and believe that steps can be taken to reduce disease risk. Tailored education efforts are needed to address potential misconceptions about risk and protective factors.
PMCID: PMC4163539  PMID: 24630852
Illness perceptions; Public understanding; Health education; National survey; Attitudes and beliefs
37.  Hidden impacts of ocean acidification to live and dead coral framework 
Cold-water corals, such as Lophelia pertusa, are key habitat-forming organisms found throughout the world's oceans to 3000 m deep. The complex three-dimensional framework made by these vulnerable marine ecosystems support high biodiversity and commercially important species. Given their importance, a key question is how both the living and the dead framework will fare under projected climate change. Here, we demonstrate that over 12 months L. pertusa can physiologically acclimate to increased CO2, showing sustained net calcification. However, their new skeletal structure changes and exhibits decreased crystallographic and molecular-scale bonding organization. Although physiological acclimatization was evident, we also demonstrate that there is a negative correlation between increasing CO2 levels and breaking strength of exposed framework (approx. 20–30% weaker after 12 months), meaning the exposed bases of reefs will be less effective ‘load-bearers’, and will become more susceptible to bioerosion and mechanical damage by 2100.
PMCID: PMC4632617  PMID: 26290073
ocean acidification; cold-water corals; climate change; biomineralization; calcification; Lophelia pertusa
38.  Fertility preservation in reproductive-age women facing gonadotoxic treatments 
Current Oncology  2015;22(4):e294-e304.
Advancements in the treatments for cancer and autoimmune and other hematologic conditions continue to improve survival and cure rates. Despite those changes, various gonadotoxic agents and other treatments can still compromise the future fertility of many women. Progress in medical and surgical reproductive technologies has helped to offset the reproductive consequences of the use of gonadotoxic therapies, and allows for future fertility and normal pregnancy.
A review of the literature was performed to outline the pathophysiology of gonadotoxicity from various treatments. The success of fertility preservation, fertility sparing, and cryopreservation options are reviewed. Barriers and facilitators to referral and oncofertility treatment in Canada are also outlined.
According to the quality of the evidence, recommendations are made for fertility assessment, patient referral, cryopreservation, and other assisted reproductive technologies.
To ensure ongoing fertility in women undergoing gonadotoxic treatments, assisted reproductive technologies can be combined with a multidisciplinary approach to patient assessment and referral.
PMCID: PMC4530827  PMID: 26300680
Oncofertility; fertility preservation; cryopreservation; gonadotoxicity; young adults; adolescents
39.  Explaining, not just predicting, drives interest in personal genomics 
Genome Medicine  2015;7(1):74.
There is a widespread assumption that risk prediction is the major driver of customer interest in personal genomic testing (PGT). However, some customers may also be motivated by finding out whether their existing diseases have a genetic etiology. We evaluated the impact of an existing medical diagnosis on customer interest in condition-specific results from PGT.
Using a prospective online survey of PGT customers, we measured customer interest prior to receiving PGT results for 11 health conditions, and examined the association between interest and personal medical history of these conditions using logistic regression.
We analyzed data from 1,538 PGT customers, mean age 48.7 years, 61 % women, 90 % White, and 47 % college educated. The proportion of customers who were ‘very interested’ in condition-specific PGT varied considerably, from 28 % for ulcerative colitis to 68% for heart disease. After adjusting for demographic and personal characteristics including family history, having a diagnosis of the condition itself was significantly associated with interest in genetic testing for risk of that condition, with odds ratios ranging from 2.07 (95 % CI 1.28-3.37) for diabetes to 19.99 (95 % CI 4.57-87.35) for multiple sclerosis.
PGT customers are particularly interested in genetic markers for their existing medical conditions, suggesting that the value of genetic testing is not only predictive, but also explanatory.
Electronic supplementary material
The online version of this article (doi:10.1186/s13073-015-0188-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4533947  PMID: 26269719
40.  Clinical use of amyloid-positron emission tomography neuroimaging: Practical and bioethical considerations 
Until recently, estimation of β-amyloid plaque density as a key element for identifying Alzheimer's disease (AD) pathology as the cause of cognitive impairment was only possible at autopsy. Now with amyloid-positron emission tomography (amyloid-PET) neuroimaging, this AD hallmark can be detected antemortem. Practitioners and patients need to better understand potential diagnostic benefits and limitations of amyloid-PET and the complex practical, ethical, and social implications surrounding this new technology. To complement the practical considerations, Eli Lilly and Company sponsored a Bioethics Advisory Board to discuss ethical issues that might arise from clinical use of amyloid-PET neuroimaging with patients being evaluated for causes of cognitive decline. To best address the multifaceted issues associated with amyloid-PET neuroimaging, we recommend this technology be used only by experienced imaging and treating physicians in appropriately selected patients and only in the context of a comprehensive clinical evaluation with adequate explanations before and after the scan.
PMCID: PMC4878065  PMID: 27239516
Alzheimer's disease; Mild cognitive impairment; Bioethics in neurology; Positron emission tomography; Diagnostic use; Dementia; Biomarkers; Amyloid-β
41.  Amyloid imaging, risk disclosure and Alzheimer’s disease: ethical and practical issues 
PET ligands that bind with high specificity to amyloid plaques represent a major breakthrough in Alzheimer’s disease (AD) research. Amyloid neuroimaging is now approved by the US FDA to aid in the diagnosis of AD, and is being used to identify amyloid-positive but asymptomatic individuals for secondary AD prevention trials. The use of amyloid neuroimaging in preclinical populations raises important ethical and practical challenges, including determining appropriate uses of this technology, evaluating the potential benefits and harms of disclosing results, and communicating effectively about testing with patients and family members. Emerging policy issues also require consideration (e.g., legal safeguards for biomarker-positive individuals). Further research is needed to inform effective and ethical implementation and regulation of amyloid imaging.
PMCID: PMC4498486  PMID: 26167204
42.  Quantitative localisation of synaptic and extrasynaptic GABAA receptor subunits on hippocampal pyramidal cells by freeze-fracture replica immunolabelling 
The European journal of neuroscience  2010;32(11):1868-1888.
Hippocampal CA1 pyramidal cells, which receive γ-aminobutyric acid (GABA)ergic input from at least 18 types of presynaptic neuron, express 14 subunits of the pentameric GABAA receptor. The relative contribution of any subunit to synaptic and extrasynaptic receptors influences the dynamics of GABA and drug actions. Synaptic receptors mediate phasic GABA-evoked conductance and extrasynaptic receptors contribute to a tonic conductance. We used freeze-fracture replica-immunogold labelling, a sensitive quantitative immunocytochemical method, to detect synaptic and extrasynaptic pools of the alpha1, alpha2 and beta3 subunits. Antibodies to the cytoplasmic loop of the subunits showed immunogold particles concentrated on distinct clusters of intramembrane particles (IMPs) on the cytoplasmic face of the plasma membrane on the somata, dendrites and axon initial segments, with an abrupt decrease in labelling at the edge of the IMP cluster. Neuroligin-2, a GABAergic synapse-specific adhesion molecule, co-labels all beta3 subunit-rich IMP clusters, therefore we considered them synapses. Double-labelling for two subunits showed that virtually all somatic synapses contain the alpha1, alpha2 and beta3 subunits. The extrasynaptic plasma membrane of the somata, dendrites and dendritic spines showed low-density immunolabelling. Synaptic labelling densities on somata for the alpha1, alpha2 and beta3 subunits were 78–132, 94 and 79 times higher than on the extrasynaptic membranes, respectively. As GABAergic synapses occupy 0.72% of the soma surface, the fraction of synaptic labelling was 33–48 (alpha1), 40 (alpha2) and 36 (beta3)% of the total somatic surface immunolabelling. Assuming similar antibody access to all receptors, about 60% of these subunits are in extrasynaptic receptors.
PMCID: PMC4487817  PMID: 21073549
dendritic spine; electron microscope; GABAergic synapse; hippocampus; immunoreactivity; inhibition
43.  Distinct Dendritic Arborization and In Vivo Firing Patterns of Parvalbumin-Expressing Basket Cells in the Hippocampal Area CA3 
Hippocampal CA3 area generates temporally structured network activity such as sharp waves and gamma and theta oscillations. Parvalbumin-expressing basket cells, making GABAergic synapses onto cell bodies and proximal dendrites of pyramidal cells, control pyramidal cell activity and participate in network oscillations in slice preparations, but their roles in vivo remain to be tested. We have recorded the spike timing of parvalbumin-expressing basket cells in areas CA2/3 of anesthetized rats in relation to CA3 putative pyramidal cell firing and activity locally and in area CA1. During theta oscillations, CA2/3 basket cells fired on the same phase as putative pyramidal cells, but, surprisingly, significantly later than downstream CA1 basket cells. This indicates a distinct modulation of CA3 and CA1 pyramidal cells by basket cells, which receive different inputs. We observed unexpectedly large dendritic arborization of CA2/3 basket cells in stratum lacunosum moleculare (33% of length, 29% surface, and 24% synaptic input from a total of ~35,000), different from the dendritic arborizations of CA1 basket cells. Area CA2/3 basket cells fired phase locked to both CA2/3 and CA1 gamma oscillations, and increased firing during CA1 sharp waves, thus supporting the role of CA3 networks in the generation of gamma oscillations and sharp waves. However, during ripples associated with sharp waves, firing of CA2/3 basket cells was phase locked only to local but not CA1 ripples, suggesting the independent generation of fast oscillations by basket cells in CA1 and CA2/3. The distinct spike timing of basket cells during oscillations in CA1 and CA2/3 suggests differences in synaptic inputs paralleled by differences in dendritic arborizations.
PMCID: PMC4473055  PMID: 23595740
44.  Could giant basin-forming impacts have killed Martian dynamo? 
Geophysical Research Letters  2014;41(22):8006-8012.
The observed strong remanent crustal magnetization at the surface of Mars suggests an active dynamo in the past and ceased to exist around early to middle Noachian era, estimated by examining remagnetization strengths in extant and buried impact basins. We investigate whether the Martian dynamo could have been killed by these large basin-forming impacts, via numerical simulation of subcritical dynamos with impact-induced thermal heterogeneity across the core-mantle boundary. We find that subcritical dynamos are prone to the impacts centered on locations within 30° of the equator but can easily survive those at higher latitudes. Our results further suggest that magnetic timing places a strong constraint on postimpact polar reorientation, e.g., a minimum 16° polar reorientation is needed if Utopia is the dynamo killer.
PMCID: PMC4459199  PMID: 26074641
Martian dynamo; giant impacts; thermal heterogeneity; numerical simulation
45.  Community-based care vs. centralised hospitalisation for MDR-TB patients KwaZulu-Natal, South Africa 
KwaZulu-Natal, South Africa a predominantly rural province with high burdens of TB, MDR-TB and HIV infection.
To determine the most effective model of care by comparing MDR-TB treatment outcomes at community-based sites with traditional care at a central, specialised hospital.
A non-randomised observational prospective cohort study comparing community-based and centralised care. Patients at community-based sites were closer to home, had easier access to care and home-based care was available from treatment initiation.
Four community-based sites treated 736 patients, while 813 were treated at the centralised hospital (a total of 1549 patients). Overall, 75% were HIV co-infected (community: 76% vs. hospitalised: 73%, p=0.45) and 86% received antiretroviral therapy (community: 91% vs. hospitalised: 82%, p=0.22).
In multivariate analysis MDR-TB patients were more likely to have a successful treatment outcome if they were treated at a community-based site (adjusted OR=1.43, p=0.01). However, there was heterogeneity in outcomes at the four community-based sites, with Site 1 demonstrating that home-based care was associated with increased treatment success of 72% compared with success of between 52 - 60% at the other three sites.
Community-based care for patients with MDR-TB was more effective than care in a central, specialised hospital. Home-based care further increased treatment success.
PMCID: PMC4324454  PMID: 25574914
Models of care; HIV; outcomes
46.  The formation of a large summertime Saharan dust plume: Convective and synoptic-scale analysis 
Haboobs are dust storms produced by the spreading of evaporatively cooled air from thunderstorms over dusty surfaces and are a major dust uplift process in the Sahara. In this study observations, reanalysis, and a high-resolution simulation using the Weather Research and Forecasting model are used to analyze the multiscale dynamics which produced a long-lived (over 2 days) Saharan mesoscale convective system (MCS) and an unusually large haboob in June 2010. An upper level trough and wave on the subtropical jet 5 days prior to MCS initiation produce a precipitating tropical cloud plume associated with a disruption of the Saharan heat low and moistening of the central Sahara. The restrengthening Saharan heat low and a Mediterranean cold surge produce a convergent region over the Hoggar and Aïr Mountains, where small convective systems help further increase boundary layer moisture. Emerging from this region the MCS has intermittent triggering of new cells, but later favorable deep layer shear produces a mesoscale convective complex. The unusually large size of the resulting dust plume (over 1000 km long) is linked to the longevity and vigor of the MCS, an enhanced pressure gradient due to lee cyclogenesis near the Atlas Mountains, and shallow precipitating clouds along the northern edge of the cold pool. Dust uplift processes identified are (1) strong winds near the cold pool front, (2) enhanced nocturnal low-level jet within the aged cold pool, and (3) a bore formed by the cold pool front on the nocturnal boundary layer.
PMCID: PMC4379907  PMID: 25844277
WRF; haboob; MCS; Sahara; dust; convection
47.  Associations between self-referral and health behavior responses to genetic risk information 
Genome Medicine  2015;7(1):10.
Studies examining whether genetic risk information about common, complex diseases can motivate individuals to improve health behaviors and advance planning have shown mixed results. Examining the influence of different study recruitment strategies may help reconcile inconsistencies.
Secondary analyses were conducted on data from the REVEAL study, a series of randomized clinical trials examining the impact of genetic susceptibility testing for Alzheimer’s disease (AD). We tested whether self-referred participants (SRPs) were more likely than actively recruited participants (ARPs) to report health behavior and advance planning changes after AD risk and APOE genotype disclosure.
Of 795 participants with known recruitment status, 546 (69%) were self-referred and 249 (31%) had been actively recruited. SRPs were younger, less likely to identify as African American, had higher household incomes, and were more attentive to AD than ARPs (all P < 0.01). They also dropped out of the study before genetic risk disclosure less frequently (26% versus 41%, P < 0.001). Cohorts did not differ in their likelihood of reporting a change to at least one health behavior 6 weeks and 12 months after genetic risk disclosure, nor in intentions to change at least one behavior in the future. However, interaction effects were observed where ε4-positive SRPs were more likely than ε4-negative SRPs to report changes specifically to mental activities (38% vs 19%, p < 0.001) and diets (21% vs 12%, p = 0.016) six weeks post-disclosure, whereas differences between ε4-positive and ε4-negative ARPs were not evident for mental activities (15% vs 21%, p = 0.413) or diets (8% versus 16%, P = 0.190). Similarly, ε4-positive participants were more likely than ε4-negative participants to report intentions to change long-term care insurance among SRPs (20% vs 5%, p < 0.001), but not ARPs (5% versus 9%, P = 0.365).
Individuals who proactively seek AD genetic risk assessment are more likely to undergo testing and use results to inform behavior changes than those who respond to genetic testing offers. These results demonstrate how the behavioral impact of genetic risk information may vary according to the models by which services are provided, and suggest that how participants are recruited into translational genomics research can influence findings.
Trial registration NCT00089882 and NCT00462917
Electronic supplementary material
The online version of this article (doi:10.1186/s13073-014-0124-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4311425  PMID: 25642295
48.  Emerging issues in public health genomics 
This review highlights emerging areas of interest in public health genomics. First, recent advances in newborn screening (NBS) are described, with a focus on practice and policy implications of current and future efforts to expand NBS programs (e.g., via next-generation sequencing). Next, research findings from the rapidly progressing field of epigenetics and epigenomics are detailed, highlighting ways in which our emerging understanding in these areas could guide future intervention and research efforts in public health. We close by considering various ethical, legal and social issues posed by recent developments in public health genomics; these include policies to regulate access to personal genomic information; the need to enhance genetic literacy in both health professionals and the public; and challenges in ensuring that the benefits (and burdens) from genomic discoveries and applications are equitably distributed. Needs for future genomics research that integrates across basic and social sciences are also noted.
PMCID: PMC4229014  PMID: 25184533
Newborn screening; epigenetics; epigenomics; bioethics; health education
49.  Increased response to morphine in mice lacking protein kinase C epsilon 
Genes, brain, and behavior  2006;6(4):329-338.
The protein kinase C (PKC) family of serine–threonine kinases has been implicated in behavioral responses to opiates, but little is known about the individual PKC isozymes involved. Here, we show that mice lacking PKCε have increased sensitivity to the rewarding effects of morphine, revealed as the expression of place preference and intravenous self-administration at very low doses of morphine that do not evoke place preference or self-administration in wild-type mice. The PKCε null mice also show prolonged maintenance of morphine place preference in response to repeated testing when compared with wild-type mice. The supraspinal analgesic effects of morphine are enhanced in PKCε null mice, and the development of tolerance to the spinal analgesic effects of morphine is delayed. The density of μ-opioid receptors and their coupling to G-proteins are normal. These studies identify PKCε as a key regulator of opiate sensitivity in mice.
PMCID: PMC4264050  PMID: 16899053
Analgesia; opioid; PKC; place preference; self-administration
50.  Design, methods, and participant characteristics of the Impact of Personal Genomics (PGen) Study, a prospective cohort study of direct-to-consumer personal genomic testing customers 
Genome Medicine  2014;6(12):96.
Designed in collaboration with 23andMe and Pathway Genomics, the Impact of Personal Genomics (PGen) Study serves as a model for academic-industry partnership and provides a longitudinal dataset for studying psychosocial, behavioral, and health outcomes related to direct-to-consumer personal genomic testing (PGT). Web-based surveys administered at three time points, and linked to individual-level PGT results, provide data on 1,464 PGT customers, of which 71% completed each follow-up survey and 64% completed all three surveys. The cohort includes 15.7% individuals of non-white ethnicity, and encompasses a range of income, education, and health levels. Over 90% of participants agreed to re-contact for future research.
Electronic supplementary material
The online version of this article (doi:10.1186/s13073-014-0096-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4256737  PMID: 25484922

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