bluuebunny/crossref_metadata_2025 huggingface dataset:
One‐way gates successfully facilitate the movement of burrowing bettongs (Bettongia lesueur) through exclusion fences around reserve
Authors: Butler Kate , Paton David , Moseby Katherine
Published: September 2018

When native herbivores are enclosed in fenced reserves without predators or dispersal options then overgrazing can occur, leading to damage to vegetation and co‐occurring fauna species. One‐way gates that allow medium‐sized herbivores to exit fenced reserves may be an effective management tool to address overabundance or facilitate population expansion. We tested the use of one‐way gates to facilitate the movement of the reintroduced burrowing bettong (Bettongia lesueur) from inside to outside a fenced reserve in arid South Australia. One‐way gates were installed in the exterior fence of the reserve and assessed using remote motion‐sensor cameras. The influence of gate position (dune, swale or corner) and provision of food were assessed in relation to gate visits and exits. Animals were trapped inside and outside the gates to determine any population bias in gate exits. Baited gates recorded significantly more exits than unbaited gates and dune gates had higher exit rates than interdunal swale gates. When gates were unbaited, those installed in corners of the reserve showed significantly higher visitation by bettongs and a non‐significant trend towards more exits compared to gates placed in straight sections of fence along dunes or swales. There was no sex or age bias of burrowing bettongs using the gates and bettongs travelled between 75 m and 1535 m from their warrens to use the gates. No non‐target species gained access to the reserve through the one‐way gates and only two non‐target animals used the gates to exit the reserve confirming gate specificity for bettongs. During the same period, 96 burrowing bettongs exited the reserve through the one‐way gates. One‐way gates may be a management strategy for facilitating passive movement of medium‐sized herbivores outside of fenced reserves for the purposes of reducing overpopulation or facilitating population expansion outside reserves.
Modelling large herbivore movement decisions: Beyond food availability as a predictor of ranging patterns
Authors: Boult Victoria L. , Sibly Richard M. , Quaife Tristan , Fishlock Vicki , Moss Cynthia , Lee Phyllis C.
Published: September 2018

The ability of animals to adapt to their changing environment will depend in part on shifts in their ranging patterns, but when and why individuals choose to move requires detailed understanding of their decision‐making processes. We develop a simple decision‐making model accounting for resource availability in habitually used ranges. We suggest that disparities between model predictions and animal tracking data indicate additional factors influencing movement decisions, which may be identified given detailed system‐specific knowledge. The model was evaluated using movement data from satellite‐tracked elephants (Loxodonta africana) inhabiting the Amboseli basin in Kenya, moving from savannah areas with low quality but constant resource availability, to areas with temporally constrained higher nutrient availability. Overall, the model fits the data well: There was a good correlation between predicted and observed locations for the combined data from all elephants, but variation between individuals in how well the model fits. For those elephants where model predictions were less successful, additional factors likely to affect movement decisions, including reproduction, anthropogenic threats, memory and perception are suggested. This protocol for building and testing decision‐making models should contribute to success in attempts to preserve sufficient space for large herbivores in their increasingly human‐dominated ecosystems.
Plasmacytoma variant translocation 1 (PVT1) regulates trophoblast viability, proliferation, and migration and is downregulated in spontaneous abortion
Authors: Qin Xiaoli , Chen Yan , Chen Shufang , Liu Xiaorui , Zeng Weihong , Tian Fuju , Lin Yi , Fan Cuifang
Published: September 2018

Problem

Human pregnancy is a complex biological process, and spontaneous abortion is the most common complication of pregnancy. LncRNAs have been identified that play key roles in a variety of human diseases. Recently, lncRNAPVT1 was reported to relate to the pathogenesis and progression of pregnancy. However, the role and underlying mechanism of PVT1 in trophoblast cell dysfunction in spontaneous abortion remain largely unknown.

Method of study

The effects of PVT1, miR‐424, and eIF5A on HTR8 cells and human villi tissues from spontaneous or induced abortions were investigated using CCK‐8 assay, EdU assay, real‐time polymerase chain reaction, Western blotting, cell transfection assays, cell migration assays, and luciferase reporter gene assays.

Results

Overexpression of PVT1 promoted HTR8 cell viability, proliferation, and migration. Suppression of PVT1 promoted miR‐424 expression, and miR‐424 could modulate the effects of PVT1 in HTR8 cells. MiR‐424 exerted its function via regulation of eIF5A expression in HTR8 cells. PVT1 and eIF5A expression were decreased and miR‐424 was increased in clinical samples from spontaneous abortion, compared to samples from elective induced abortion.

Conclusion

PVT1 regulates trophoblast cell function via modulation of a PVT1/miR‐424/eIF5A pathway.
Long‐term follow‐up of ICSI‐conceived offspring compared with spontaneously conceived offspring: a systematic review of health outcomes beyond the neonatal period
Authors: Catford S. R. , McLachlan R. I. , O'Bryan M. K. , Halliday J. L.
Published: September 2018

Background

A significant increase in the use of intracytoplasmic sperm injection (ICSI) since its introduction in 1992 has been observed worldwide, including beyond its original intended use for severe male factor infertility. Concerns regarding ICSI include the effects of poor quality spermatozoa on offspring health and future fertility, and of the technique itself. The health and development of ICSI‐conceived children beyond early infancy have not been comprehensively assessed.

Objective

A systematic review of health outcomes of ICSI‐conceived offspring beyond the neonatal period compared to spontaneously conceived (SC) offspring.

Design

PubMed, OVID Medline/Embase, InformIT, Web of Science, and ProQuest databases were searched for studies reporting on health outcomes in ICSI‐conceived offspring beyond 28 days after birth.

Main outcomes measure(s)

Physical and psychosocial health.

Results

The search strategy yielded 2826 articles. Of these, 2580 were not relevant or did not meet inclusion criteria and 138 were duplicates. One hundred and eight full‐text papers were evaluated further, and 48 satisfied the inclusion criteria. Most studies reported on neurodevelopment during early infancy and childhood with reassuring results. Growth, vision, and hearing of ICSI and SC offspring also appear comparable, although important differences in general physical health, and particularly metabolic and reproductive health have been described, including recently poorer semen quality among ICSI‐conceived young adult men compared to SC peers.

Conclusion

Whilst neurodevelopment, growth, vision, and hearing appear similar between ICSI and SC children, evidence suggests differences in general physical health, and metabolic and reproductive endpoints. The clinical significance of many findings, however, remains unclear, and further prospective, large, and good quality studies with a focus on all these health outcomes in ICSI‐conceived young adults are required.
Autism Spectrum Disorder symptomatology in children with Mucopolysaccharide Disease Type III
Authors: Wolfenden Claire , Wittkowski Anja , Jones Simon A. , Rust Stewart , Hare Dougal J.
Published: September 2018

Accessible Summary

We now have a much better understanding of the specific characteristics of the many and often rare conditions that are associated with intellectual disabilities [learning disabilities]

We examined a condition called Mucopolysaccharidosis Type III [MPS III] sometimes called Sanfilippo syndrome

Many children with MPS III also appear to show signs of autism but an additional diagnosis of autism is time‐consuming and not always available to families

We, therefore, measured autistic symptoms in children with MPS III and found that they often had problems in social responsiveness

Children with MPS III and their families might therefore routinely benefit from the types of support offered to children with autism

Symptoms of autism spectrum disorder (ASD) are present in children with mucopolysaccharidosis type III (MPS III). Questionnaires measuring the two core domains of ASD (social responsiveness and repetitive behaviour) were completed by N = 17 parents of children with MPS III. Results indicated that scores consistent with ASD were reported by all parents on a measure of social responsiveness but lower scores were reported for repetitive behaviour. The findings provide support for the provision of additional interventions, focusing on social and communication difficulties, for children with MPS III across all phases of their disorder.
High‐fructose corn syrup consumption in adolescent rats causes bipolar‐like behavioural phenotype with hyperexcitability in hippocampal CA3‐CA1 synapses
Authors: Alten Baris , Yesiltepe Metin , Bayraktar Erva , Tas Sadik Taskin , Gocmen Ayse Yesim , Kursungoz Canan , Martinez Ana , Sara Yildirim
Published: September 2018

Background and Purpose

Children and adolescents are the top consumers of high‐fructose corn syrup (HFCS) sweetened beverages. Even though the cardiometabolic consequences of HFCS consumption in adolescents are well known, the neuropsychiatric consequences have yet to be determined.

Experimental Approach

Adolescent rats were fed for a month with 11% weight/volume carbohydrate containing HFCS solution, which is similar to the sugar‐sweetened beverages of human consumption. The metabolic, behavioural and electrophysiological characteristics of HFCS‐fed rats were determined. Furthermore, the effects of TDZD‐8, a highly specific GSK‐3B inhibitor, on the HFCS‐induced alterations were further explored.

Key Results

HFCS‐fed adolescent rats displayed bipolar‐like behavioural phenotype with hyperexcitability in hippocampal CA3‐CA1 synapses. This hyperexcitability was associated with increased presynaptic release probability and increased readily available pool of AMPA receptors to be incorporated into the postsynaptic membrane, due to decreased expression of the neuron‐specific α3‐subunit of Na+/K+‐ATPase and an increased ser845‐phosphorylation of GluA1 subunits (AMPA receptor subunit) respectively. TDZD‐8 treatment was found to restore behavioural and electrophysiological disturbances associated with HFCS consumption by inhibition of GSK‐3B, the most probable mechanism of action of lithium for its mood‐stabilizing effects.

Conclusion and Implications

This study shows that HFCS consumption in adolescent rats led to a bipolar‐like behavioural phenotype with neuronal hyperexcitability, which is known to be one of the earliest endophenotypic manifestations of bipolar disorder. Inhibition of GSK‐3B with TDZD‐8 attenuated hyperexcitability and restored HFCS‐induced behavioural alterations.
Ceftazidime‐Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups
Authors: Li Jianguo , Lovern Mark , Green Michelle L. , Chiu Joannellyn , Zhou Diansong , Comisar Craig , Xiong Yuan , Hing Jeremy , MacPherson Merran , Wright James G. , Riccobene Todd , Carrothers Timothy J. , Das Shampa
Published: September 2018

Ceftazidime‐avibactam is a novel β‐lactam/β‐lactamase inhibitor combination for the treatment of serious infections caused by resistant gram‐negative pathogens. Population pharmacokinetic (PopPK) models were built to incorporate pharmacokinetic (PK) data from five phase III trials in patients with complicated intra‐abdominal infection (cIAI), complicated urinary tract infection (cUTI), or nosocomial (including ventilator‐associated) pneumonia. Ceftazidime and avibactam pharmacokinetics were well‐described by two‐compartment disposition models, with creatinine clearance (CrCL) the key covariate determining clearance variability. Steady‐state ceftazidime and avibactam exposure for most patient subgroups differed by ≤ 20% vs. healthy volunteers. Probability of PK/pharmacodynamic (PD) target attainment (free plasma ceftazidime > 8 mg/L and avibactam > 1 mg/L for ≥ 50% of dosing interval) was ≥ 94.9% in simulations for all patient subgroups, including indication and renal function categories. No exposure‐microbiological response relationship was identified because target exposures were achieved in almost all patients. These modeling results support the approved ceftazidime‐avibactam dosage regimens (2000‐500 mg every 8 hours, adjusted for CrCL ≤ 50 mL/min).
Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps
Authors: Gidaro Teresa , Servais Laurent
Published: September 2018

Spinal muscular atrophy (SMA) is a recessive disorder caused by a mutation in the survival motor neuron 1 gene (SMN1); it affects 1 in 11 000 newborn infants. The most severe and most common form, type 1 SMA, is associated with early mortality in most cases and severe disability in survivors. Nusinersen, an antisense oligonucleotide, promotes production of full‐length protein from the pseudogene SMN2. Nusinersen treatment prolongs survival of patients with type 1 SMA and allows motor milestone acquisition. Patients with type 2 SMA also show progress on different motor scales after nusinersen treatment. Nusinersen was recently approved by the European Medicines Agency and the US Food and Drug Administration; it is now reimbursed in several European countries and in the USA. In Australia, the transition from expanded access programme to commercial availability is coming soon. In New Zealand, an expanded access programme is opened, and in Canada price negotiation for the treatment is in progress. In this review we exemplify the clinical benefit of nusinersen in subgroups of patients with SMA. Nusinersen represents the first efficacious marked approved drug in type 1 and type 2 SMA. Different knowledge gaps, such as results in older patients, in patients with permanent ventilation, in patients with neonatal forms, or in patients after spinal fusion, still need to be addressed.

What this paper adds

Identifies gaps in knowledge about the efficacy of nusinersen in broader populations of patients with spinal muscular atrophy.

Identifies open questions in populations of patients where proof of efficacy is available.
Reduction in insulin degludec dosing for multiple exercise sessions improves time spent in euglycaemia in people with type 1 diabetes: A randomized crossover trial
Authors: Moser Othmar , Eckstein Max L. , Mueller Alexander , Birnbaumer Philipp , Aberer Felix , Koehler Gerd , Sourij Caren , Kojzar Harald , Holler Peter , Simi Helmut , Pferschy Peter , Dietz Pavel , Bracken Richard M. , Hofmann Peter , Sourij Harald
Published: September 2018

Aims

To compare the time spent in specified glycaemic ranges in people with type 1 diabetes (T1D) during 5 consecutive days of moderate‐intensity exercise while on either 100% or 75% of their usual insulin degludec (IDeg) dose.

Materials and Methods

Nine participants with T1D (four women, mean age 32.1 ± 9.0 years, body mass index 25.5 ± 3.8 kg/m2, glycated haemoglobin 55 ± 7 mmol/mol (7.2% ± 0.6%) on IDeg were enrolled in the trial. Three days before the first exercise period, participants were randomized to either 100% or 75% of their usual IDeg dose. Participants exercised on a cycle ergometer for 55 minutes at a moderate intensity for 5 consecutive days. After a 4‐week wash‐out period, participants performed the last exercise period for 5 consecutive days with the alternate IDeg dose. Time spent in specified glycaemic ranges, area under the curve and numbers of hypoglycaemic events were compared for the 5 days on each treatment allocation using a paired Students' t test, Wilcoxon matched‐pairs signed‐rank test and two‐way ANOVA.

Results

Time spent in euglycaemia over 5 days was greater for the 75% IDeg dose versus the 100% IDeg dose (4008 ± 938 minutes vs. 3566 ± 856 minutes; P = 0.04). Numbers of hypoglycaemic events (P = 0.91) and time spent in hypoglycaemia (P = 0.07) or hyperglycaemia (P = 0.38) was similar for both dosing schemes.

Conclusions

A 25% reduction in usual IDeg dose around regular exercise led to more time spent in euglycaemia, with small effects on time spent in hypo‐ and hyperglycaemia.
A NEW MONETARIST MODEL OF FIAT AND E‐MONEY
Authors: Lotz Sébastien , Vasselin Françoise
Published: September 2018

We develop a dual payment New Monetarist model, where an electronic money (e‐purse) competes with fiat money (cash). The two payment instruments differ in terms of security, cost, and acceptability. Strategic complementarities lead to multiple monetary equilibria. We establish the conditions under which e‐money can coexist with, or replace fiat money, and explain the reasons for the e‐purse failure/success in a few countries. We also compare welfare when one currency or both circulate. When the risk of theft of cash is endogenous, e‐money cannot replace cash entirely; however, low inflation can facilitate the adoption of e‐money in parallel with fiat money. (JEL D83, E40, E50)
Ten lessons from a quarter of a century of post‐communist economic transformation
Authors: Åslund Anders
Published: September 2018

The dominant idea in the early post‐communist economic transition was that an early and comprehensive radical economic reform programme was needed. This program was accompanied by a clear programme of political economy reform, which included; a clear understanding that the old system was finished, a political breakthrough, new political leaders, new economic policymakers, the swift elaboration of a reform programme, a functioning parliament, sufficient international financial support, fast implementation, public understanding, and the overruling of any need for consensus. In hindsight, all of these factors worked when they were present. Critics warned of too sharp an output fall, which did not come to pass, lagging institutional development, and neglect of social reforms. The biggest problem has become the absence of real property rights because of captured judicial systems in the post‐communist countries not belonging to the European Union.
Potential landscape‐scale pollinator networks across Great Britain: structure, stability and influence of agricultural land cover
Authors: Redhead John W. , Woodcock Ben A. , Pocock Michael J.O. , Pywell Richard F. , Vanbergen Adam J. , Oliver Tom H.
Published: September 2018

Understanding spatial variation in the structure and stability of plant–pollinator networks, and their relationship with anthropogenic drivers, is key for maintaining pollination services and mitigating declines. Constructing sufficient networks to examine patterns over large spatial scales remains challenging. Using biological records (citizen science), we constructed potential plant–pollinator networks at 10 km resolution across Great Britain, comprising all potential interactions inferred from recorded floral visitation and species co‐occurrence. We calculated network metrics (species richness, connectance, pollinator and plant generality) and adapted existing methods to assess robustness to sequences of simulated plant extinctions across multiple networks. We found positive relationships between agricultural land cover and both pollinator generality and robustness to extinctions under several extinction scenarios. Increased robustness was attributable to changes in plant community composition (fewer extinction‐prone species) and network structure (increased pollinator generality). Thus, traits enabling persistence in highly agricultural landscapes can confer robustness to potential future perturbations on plant–pollinator networks.
Refractory juvenile myoclonic epilepsy: a meta‐analysis of prevalence and risk factors
Authors: Stevelink R. , Koeleman B. P. C. , Sander J. W. , Jansen F. E. , Braun K. P. J.
Published: September 2018

Background and purpose

Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome for which treatment response is generally assumed to be good. We aimed to determine the prevalence and prognostic risk factors for refractoriness of JME.

Methods

We systematically searched PubMed and EMBASE and included 43 eligible studies, reporting seizure outcome after antiepileptic drug (AED) treatment in JME cohorts. We defined refractory JME as persistence of any seizure despite AED treatment and performed a random‐effects meta‐analysis to assess the prevalence of refractory JME and of seizure recurrence after AED withdrawal in individuals with well‐controlled seizures. Studies reporting potential prognostic risk factors in relation to seizure outcome were included for subsequent meta‐analysis of risk factors for refractoriness.

Results

Overall, 35% (95% confidence interval, 29–41%) of individuals (n = 3311) were refractory. There was marked heterogeneity between studies. Seizures recurred in 78% (95% confidence interval, 52–94%) of individuals who attempted to withdraw from treatment after a period of seizure freedom (n = 246). Seizure outcome by publication year suggested that prognosis did not improve over time. Meta‐analysis suggested six variables as prognostic factors for refractoriness, i.e. having three seizure types, absence seizures, psychiatric comorbidities, earlier age at seizure onset, history of childhood absence epilepsy and praxis‐induced seizures.

Conclusion

One‐third of people with JME were refractory, which is a higher prevalence than expected. Risk factors were identified and can be used to guide treatment and counselling of people with JME.
Influence of environmental conditions on the reproductive success and recruitment of the Argentine hake Merluccius hubbsi (southwestern Atlantic Ocean)
Authors: Marrari Marina , Macchi Gustavo J. , Santos Betina , Leonarduzzi Ezequiel
Published: September 2018

The Argentine hake Merluccius hubbsi represents the dominant demersal fish and one of the main fisheries in the Argentine Sea. We analyzed over 17 years (September 1997–February 2015) of satellite surface chlorophyll concentration (CHL) and sea surface temperature anomaly (SSTA) data in the main spawning (SUB) and nursery (SJG) areas of the Patagonian stock of M. hubbsi. The variability observed in these environmental conditions was related to interannual differences in the reproductive success of hake. CHL values were maximum during austral spring (October–November) and minimum during winter (June–August). Blooms started in late September and lasted on average 128 and 110 days at SUB and SJG, respectively. At SUB, average CHL at the time of reproduction, the day of occurrence of the maximum chlorophyll concentration, and fall SST anomalies were significantly related to recruitment (RVPA) a year later and to two Larval Survival Indices (LSISSB and LSITEP) considered. At SJG, RVPA, LSISSB, and LSITEP showed negative correlations with fall (March–May) SSTA. Total egg production was not related to fall SSTA or spring phytoplankton dynamics at SUB or SJG. Significant positive trends were observed in the time series of CHL and SSTA in the study area. The trends observed in CHL represent average increases of 40.7% and 35.7% since 1997 at SUB and SJG, respectively. The potential implications of long‐term changes in environmental conditions for hake reproductive success are discussed.
Operational oceanography applied to skipjack tuna (Katsuwonus pelamis) habitat monitoring and fishing in south‐western Atlantic
Authors: Coletto Juliano Lauser , Pinho Marcelo Peres , Madureira Lauro Saint Pastous
Published: September 2018

Skipjack tuna (Katsuwonus pelamis) ranks third among marine resources that sustain global fisheries. This study delimits the spatiotemporal habitat of the species in the south‐western Atlantic Ocean, based on operational oceanography. We used generalized additive models (GAMs) and catch data from six pole‐and‐line fishing vessels operating during 2014 and 2015 fishing seasons to assess the effect of environmental variables on catch. We also analysed Modis sensor images of sea surface temperature (SST) and surface chlorophyll‐α concentration (SCC) to describe fishing ground characteristics in time and space. Catch was positively related to thermocline depth (24–45 m), SST (22–24.5°C), SCC (0.08–0.14 mg/m³) and salinity (34.9–35.8). Through SST images, we identified that thermal fronts were the main surface feature associated with a higher probability to find skipjack. Also, we state that skipjack fishery is tightly related to shelf break because bottom topography drives the position of fronts in this area. Ocean colour fronts and plankton enrichment were important proxies, accessible through SCC, used to delineate skipjack fishing grounds. Catch per unit effort (CPUE) was higher towards summer (median 14 t/fishing day) due to the oceanographic characteristics of the southern region. High productivity in this sector of the Brazilian coast defines the main skipjack feeding areas and, as a consequence, the greatest abundance and availability for fishing.
Just a FAD? Ecosystem impacts of tuna purse‐seine fishing associated with fish aggregating devices in the western Pacific Warm Pool Province
Authors: Griffiths Shane P. , Allain Valerie , Hoyle Simon D. , Lawson Tim A. , Nicol Simon J.
Published: September 2018

The western and central Pacific Ocean supports the world's largest tuna fisheries. Since the 1990s, the purse‐seine fishery has increasingly fished in association with fish aggregating devices (FADs), which has increased catches of juvenile bigeye and yellowfin tunas and vulnerable bycatch species (e.g., sharks). This has raised concerns regarding the sustainability of these species’ populations and the supporting ecosystem, but may provide improved food security of Pacific Island nations through utilisation of FAD‐associated byproduct species (e.g., wahoo). An ecosystem model of the western Pacific Warm Pool Province was used to explore the potential ecological impacts of varying FAD fishing effort (±50% or 100%) over 30 years. The ecosystem has undergone a significant change in structure since 1980 from heavy exploitation of top predators (e.g., tunas) and “fishing up the food web” of high‐trophic‐level non‐target species. The ecosystem appeared resistant to simulated fishing perturbations, with only modest changes (<10%) in the biomass of most groups, although some less productive shark bycatch species decreased by up to 43%, which had a subsequent positive effect on several byproduct species, the prey of sharks. Reduction of FAD effort by at least 50% was predicted to increase the biomass of tuna species and sharks and return the ecosystem structure to a pre‐industrial‐fishing state within 10 years. Spatial disaggregation of the model and integration of economic information are recommended to better capture ecological and economic changes that may result from fishing and/or climate impacts and to develop appropriate management measures in response.
Coaching, Counseling, Case-Working: Do They Help the Older Unemployed Out of Benefit Receipt and Back Into the Labor Market?
Authors: Boockmann Bernhard , Brändle Tobias
Published: September 2018

Intensified counseling, job search assistance and related policies have been found to be effective for labor market integration of the unemployed by a large number of studies, but the evidence for older and hard-to-place unemployed is more mixed. In this paper, we present key results for a large-scale active labor market program directed at the older unemployed in Germany. To identify the treatment effects, we exploit regional variation in program participation. We use a combination of different evaluation estimators to check the sensitivity of the results to selection, substitution and local labor market effects. We find positive effects of the program in the range of 5-10 percentage points on integration into unsubsidized employment. However, there are also substantial lock-in effects, such that program participants have a higher probability of remaining on public welfare benefit receipt for up to 1 year after commencing the program.
Frailty state transitions and associated factors in South Australian older adults
Authors: Thompson Mark Q , Theou Olga , Adams Robert J , Tucker Graeme R , Visvanathan Renuka
Published: September 2018

Aim

Frailty is a state of decreased physiological reserve and vulnerability to stressors. Understanding the characteristics of those most at risk of worsening, or likely to improve their frailty status, are key elements in addressing this condition. The present study measured frailty state transitions and factors associated with improvement or worsening frailty status in the North West Adelaide Health Study.

Methods

Frailty was measured using the frailty phenotype (FP) and a 34‐item frailty index (FI) for 696 community‐dwelling participants aged ≥65 years, with repeated measures at 4.5‐year follow up.

Results

Improvement in frailty state was common for both tools (FP 15.5%; FI 7.9%). The majority remained stable (FP 44.4%; FI 52.6%), and many transitioned to a worse level of frailty (FP 40.1%; FI 39.5%). For both measures, multimorbidity was associated with worsening frailty among non‐frail participants. Among pre‐frail participants, normal waist circumference was associated with improvement, whereas older age was associated with worsening of frailty status. Among frail individuals, younger age was associated with improvement, and male sex and older age were associated with worsening frailty status.

Conclusions

Frailty is a dynamic process where improvement is possible. Multimorbidity, obesity, age and sex were associated with frailty transitions for both tools. Geriatr Gerontol Int 2018; 18: 1549–1555.
Associations between muscle mass, physical activity and dietary behaviour in adolescents
Authors: Hao G. , Pollock N. K. , Harris R. A. , Gutin B. , Su S. , Wang X.
Published: September 2018

Background and objectives

Investigations in older individuals suggest that adequate nutrition and physical activity are particularly important to skeletal muscle health; however, data in adolescents are scant and equivocal. The objective was to determine the associations among diet, physical activity and skeletal muscle mass in adolescents.

Methods

We assessed diet with four to seven 24‐h recalls and physical activity by accelerometry in 640 adolescents. Using total body measures of fat‐free soft tissue mass and fat mass assessed by dual‐energy X‐ray absorptiometry, the skeletal muscle mass index (SMMI) was derived by adjusting fat‐free soft tissue mass for fat mass in addition to height.

Results

Skeletal muscle mass index (SMMI) was negatively associated with consumption of sugar‐sweetened beverages (standardized beta coefficient [β] = −0.10, P = 0.001) and saturated fats (β = −0.28, P < 0.001). SMMI was positively associated with physical activity (moderate + vigorous) (β = 0.20, P < 0.001). In further analysis, we observed a significant interaction between physical activity and sugar‐sweetened beverage intake on SMMI (P = 0.002).

Conclusion

Our study in adolescence suggests that physical activity and consumption of both sugar‐sweetened beverages and saturated fats are associated with skeletal muscle mass. More importantly, our findings suggest that sugar‐sweetened beverage intake may attenuate the beneficial effects of physical activity on skeletal muscle mass.
Comparison of the gut microbiota of captive common bottlenose dolphins Tursiops truncatus in three aquaria
Authors: Suzuki A. , Segawa T. , Sawa S. , Nishitani C. , Ueda K. , Itou T. , Asahina K. , Suzuki M.
Published: September 2018

Aims

This study was conducted to assess the presence and extent of differences in the gut microbiota of common bottlenose dolphins depending on rearing facilities.

Methods and Results

Faecal samples were collected from 16 common bottlenose dolphins at three aquaria in Japan. After extracting DNA from the faeces, the V3–V4 region of bacterial 16S rRNA was amplified and sequenced using Illumina MiSeq platform. The constituent phyla of the gut microbiota were similar among aquaria; however, the most dominant phylum differed depending on the facility, and the compositions of microbiota were remarkably varied at the family level among aquaria. The alpha diversity indices tended to differ among aquaria. Some bacterial families observed in terrestrial mammalian carnivores or carnivorous fish were detected, as well as several bacterial species suspected of being pathogenic in dolphins.

Conclusion

Our findings indicate that captive environmental conditions including prey and housing types may contribute to differences in the gut microbiota of the dolphins.

Significance and Impact of the Study

This is the first study revealing the differences in gut microbiota of captive dolphins among facilities. Our findings will provide valuable information for improving the health management of dolphins.
Cumulative Antidepressant Use and Risk of Dementia in a Prospective Cohort Study
Authors: Heath Laura , Gray Shelly L. , Boudreau Denise M. , Thummel Ken , Edwards Karen L. , Fullerton Stephanie M. , Crane Paul K. , Larson Eric B.
Published: September 2018

OBJECTIVES

To determine whether antidepressant use is associated with dementia risk.

DESIGN

Prospective cohort study.

SETTING

Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system.

PARTICIPANTS

Community‐dwelling individuals aged 65 and older without dementia and with 10 years or more of KPWA enrollment at baseline (N=3,059).

MEASUREMENTS

Primary exposures were selective serotonin reuptake inhibitors (paroxetine vs other), tricyclic antidepressants, and serotonin antagonist and reuptake inhibitors. Using health plan pharmacy data, we calculated cumulative medication exposure, defined as total standardized daily doses (TSDDs), over rolling 10‐year windows. Exposure in the most recent year was excluded to avoid use related to prodromal symptoms. The Cognitive Abilities Screening Instrument was administered every 2 years; low scores triggered clinical evaluation and consensus diagnosis procedures. Dementia risk was estimated according to medication use using Cox proportional hazards models.

RESULTS

During a mean follow‐up of 7.7 years, 775 participants (25%) developed dementia; 659 (22%) developed possible or probable Alzheimer's disease. Individual antidepressant classes were not associated with differences in dementia risk, although paroxetine use was associated with higher risk of dementia for all TSDD categories than no use (0–90 TSDDs: hazard ratio (HR)=1.69, 95% confidence interval (CI)=1.18–2.42; 91–365 TSDDs: HR=1.40, 95% CI=0.88–2.23; 366–1095 TSDDs: HR=2.13, 95% CI=1.32–3.43; ≥1095 TSDDs: HR=1.42, 95% CI=0.82–2.46).

CONCLUSION

Most commonly prescribed nonanticholinergic depression medications used in late life do not appear to be associated with dementia risk. Paroxetine and other anticholinergic antidepressants may be exceptions in older individuals. Future studies are warranted to improve scientific understanding of potential associations in other settings and populations.
The Impact of Bank Credit on Labor Reallocation and Aggregate Industry Productivity
Authors: BAI JOHN (JIANQIU) , CARVALHO DANIEL , PHILLIPS GORDON M.
Published: September 2018

We provide evidence that the deregulation of U.S. state banking markets leads to a significant increase in the relative employment and capital growth of local firms with higher productivity, and that this effect is concentrated among young firms. Using financial data for a broad range of firms, our analysis suggests that this effect is driven by a shift in the composition of local bank credit supply toward more productive firms. We estimate that this effect translates into economically important gains in aggregate industry productivity and that changes in the allocation of labor play a central role in driving these gains.
Variations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil
Authors: Rossi Á. D. , Faucz F. R. , Melo A. , Pezzuto P. , de Azevedo G. S. , Schamber‐Reis B. L. F. , Tavares J. S. , Mattapallil J. J. , Tanuri A. , Aguiar R. S. , Cardoso C. C. , Stratakis C. A.
Published: September 2018

Background

Vertical transmission of Zika virus (ZIKV) is associated with congenital malformations but the mechanism of pathogenesis remains unclear. Although host genetics appear to play a role, no genetic association study has yet been performed to evaluate this question. In order to investigate if maternal genetic variation is associated with Congenital Zika Syndrome (CZS), we conducted a case–control study in a cohort of Brazilian women infected with ZIKV during pregnancy.

Methods

A total of 100 women who reported symptoms of zika during pregnancy were enrolled and tested for ZIKV. Among 52 women positive for ZIKV infection, 28 were classified as cases and 24 as controls based on the presence or absence of CZS in their infants. Variations in the coding region of 205 candidate genes involved in cAMP signaling or immune response were assessed by high throughput sequencing and tested for association with development of CZS.

Results

From the 817 single nucleotide variations (SNVs) included in association analyses, 22 SNVs in 17 genes were associated with CZS under an additive model (alpha = 0.05). Variations c.319T>C (rs11676272) and c.1297G>A, located at ADCY3 and ADCY7 genes showed the most prominent effect. The association of ADCY3 and ADCY7 genes was confirmed using a Sequence Kernel Association Test to assess the joint effect of common and rare variations, and results were statistically significant after adjustment for multiple comparisons (P < 0.002).

Conclusion

These results suggest that maternal ADCY genes contribute to ZIKV pathogenicity and influence the outcome of CZS, being promising candidates for further replication studies and functional analysis.
Resistance to activated protein C caused by the R506Q mutation in the gene for factor V is a common risk factor for venous thrombosis
Authors: DAHLBÄCK B.
Published: September 2018

The protein C system is an important natural anticoagulant pathway. Protein C is the key component of the system and it is activated by thrombin bound to thrombomodulin on the surface of endothelial cells. Activated protein C (APC) inhibits coagulation by cleaving and inactivating coagulation factors factor Va and factor Villa. Until recently, the major genetic causes of familial venous thrombophilia were inherited deficiencies of protein C, protein S or antithrombin, but together they were found in less than 5‐10% of patients with thrombosis. In 1993, the situation changed drastically with the description of inherited APC‐resistance as a novel risk factor for venous thrombosis. APC‐resistance is characterized by a poor anticoagulant response to APC. Inherited APC‐resistance is the most common genetic risk factor for this disease and it is found in 20‐60% of patients. The condition is caused by a single point mutation in the gene for factor V which predicts substitution of arginine (R) at position 506 with a glutamine (Q). Mutated factor V (FVR506Q, FV:Q506 or FV Leiden) expresses normal procoagulant properties but is partially resistant to APC. The resulting hypercoagulable state confers a life‐long increased risk of venous but not arterial thrombosis. The FVR506Q mutation is common in Caucasians with a prevalence of 1‐15%, whereas it is not found in other human races. The FVR506Q mutation may, due to its high prevalence, be an additional risk factor in individuals carrying other inherited defects such as deficiency of protein S, protein C or antithrombin. Such individuals have a high incidence of thrombosis and severe thrombophilia is a multigenetic disease. The high prevalence of inherited APC‐resistance and the availability of easy functional and genetic tests will stimulate the development of prophylactic regimens and hopefully result in a decreased incidence of thrombosis.
Transport proteins in drug resistance: biology and approaches to circumvention
Authors: TWENTYMAN P.R.
Published: September 2018

At least two transport proteins, P‐glycoprotein (Pgp) and the multidrug resistance associated protein (MRP), are believed to play a significant role in clinical resistance to cytotoxic therapy. These proteins are expressed at relatively high levels in a number of malignant diseases including various types of leukaemias. They are variably expressed on both the plasma membrane and intracellular vesicular membranes resulting in cellular drug efflux or vesicular drug sequestration, respectively. The action of MRP as a drug transporter depends on intracellular levels of glutathione. A number of strategies for circumvention of these drug resistance mechanisms have been developed and some of these are now in clinical trial.

[Note: In this paper, references are used to direct the reader to recent reviews rather than acknowledging the original work of very many authors.]
New therapies for the haemoglobinopathies
Authors: LOUKOPOULOS D.
Published: September 2018

Re‐activation of the fetal globin genes is the most realistic approach to correct the deranged pathophysiology of the haemoglobinopathies because the presence of γ‐chains can neutralize the toxic effects of the unbound α‐globin chains in the β‐thalassaemias and inhibit the polymerization of Hb S in the sickle cell syndromes. Re‐induction of fetal haemoglobin synthesis can be brought about either by direct activation of the respective promoter genes and possibly other positively acting elements, or by recruitment into proliferation and differentiation of a population of erythroid precursors which retain the γ‐chain synthesis programme but remain dormant in the bone marrow of the adult unless called up in cases of acute erythroid expansion. Examples of the first group include the butyric acid and derivatives and 5’ azacytidine. The second group comprises erythropoietin and a series of cytostatics, with hydroxyurea as the main representative. The activity of most of the above agents has already been studied in cell cultures and animals and confirmed in several patients, both at the haematological and biochemical level as well as through their frank clinical improvement. However, application of these drugs at large is not yet justified because a series of questions concerning their long‐term efficacy, the correct dosage and timing, their tolerance and toxicity, and the potential long‐term dangers, including mutagenicity are still unresolved.
Familial thrombophilia: genetic risk factors and management
Authors: MAKRIS M. , ROSENDAAL F.R. , PRESTON F.E.
Published: September 2018

There are now a number of potential candidates for inherited thrombophilia but a definite causal relationship has been established for only a proportion of these. Accepted causes of familial thrombophilia include the factor V Leiden defect and the prothrombin 20210 G>A variant, as well as deficiencies of antithrombin, protein C and protein S. Together these inherited abnormalities account for 30–50% of individuals presenting with venous thromboembolism. Factor V Leiden, which is present in up to 7% of the European population, is the most common cause of familial thrombophilia. On a worldwide basis its prevalence varies greatly with ethnic origin. In common with other types of familial thrombophilia the frequency of factor V Leiden is highly dependent on the population group studied. Venous thromboembolism, present in approximately 55% of individuals with familial coagulation inhibitor deficiencies, is the predominant clinical manifestation of familial thrombophilia. There are indications that the venous thrombotic risk is somewhat less in those with factor V Leiden. The thrombotic risk is markedly increased in those with combined defects and in those who are homozygous for factor V Leiden. Risk factors for thrombosis include pregnancy, including the puerperium, surgery, oral contraceptive usage and prolonged periods of immobilization. A substantial proportion of venous thrombotic events may occur spontaneously, i.e. without an obvious precipitating event. The management of patients with familial thrombophilia comprises counselling, thromboprophylaxis and thrombosis treatment. Although the immediate treatment of an acute thrombotic event is not significantly different from that of patients without recognised abnormalities, detailed patient management is seriously hampered by a lack of appropriate clinical trials. Prospective clinical studies, designed to ascertain individual thrombotic risk and to evaluate different therapeutic strategies are urgently required.
Gene therapy of haematopoietic cells
Authors: KARLSSON S.
Published: September 2018

Gene therapy of haematopoietic stem cells (HSCs) has been under investigation for 15 years. HSCs can be easily transduced with retroviral vectors (Moloney murine leukaemia virus = MMLV) in the mouse and expression of transferred genes can be achieved in long‐term reconstituted mice. While human haematopoietic progenitor cells can be transduced with high efficiency using amphotropic MMLV retroviral vectors, and expression of the transferred gene is easily obtained in their progeny cells, it has proven problematic to transfer genes efficiently into the HSCs of humans in clinical trials. Efforts are now under way, in many laboratories, to increase the gene transfer efficiency of retroviral vectors, or alternatively, to develop new vectors that can transduce quiescent human HSCs with higher efficiency than is currently possible. This brief review will address the two main research areas that are being explored. Firstly, investigations in human haematopoiesis to gain understanding into the molecular and cellular mechanisms that control HSC behaviour in vitro and in vivo. Secondly, development of new vectors that can transfer genes to quiescent human HSCs.
Oral health and access to dental care among older homeless adults: results from the HOPE HOME study
Authors: Freitas Daniel J. , Kaplan Lauren M. , Tieu Lina , Ponath Claudia , Guzman David , Kushel Margot
Published: September 2018

Objectives

To describe the prevalence of and factors associated with oral health measures in a sample of older homeless adults in Oakland, CA.

Methods

We conducted a cross‐sectional analysis of data from a population‐based study of 350 homeless adults aged ≥50 in which trained researchers conducted structured interviews using validated questions regarding sociodemographics, health‐related behaviors, healthcare utilization, and health status. We assessed self‐reported tooth loss, oral pain, and unmet need for dental care. We used multivariable logistic regression to examine factors associated with missing half or more teeth.

Results

Over half 201/350 (57.4 percent) of participants were missing at least half of their teeth. Half 191/350 (54.6 percent) reported oral pain in the past 6 months; 101/350 (28.9 percent) reported that oral pain prevented them from eating and 73/350 (20.9 percent) reported that pain prevented sleeping. Almost half, 141/350 (40.3 percent), had not seen a dentist in over 5 years, and over half 190/350 (54.3 percent) reported being unable to obtain needed dental care. In multivariate models, increased age (AOR = 1.09, 95 percent CI 1.04–1.14), moderate‐to‐high risk alcohol use (AOR = 2.17, CI = 1.23–3.84), moderate‐to‐high risk cocaine use (AOR = 1.72, CI = 1.03–2.88), and ever smoking (AOR = 2.87, CI = 1.59–5.18) were associated with an increased odds of having lost half or more teeth.

Conclusions

Tooth loss and oral pain are highly prevalent in older homeless adults. Increasing age, alcohol, drug, and tobacco use are associated with tooth loss.