Warmblood fragile foal syndrome type 1 mutation (PLOD1 c.2032G>A) is not associated with catastrophic breakdown and has a low allele frequency in the Thoroughbred breed.

BackgroundCatastrophic fractures are among the most common cause of fatalities in racehorses. Several factors, including genetics, likely contribute to increased risk for fatal injuries. A variant in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase1 gene (PLOD1 c.2032G>A) was shown to cause Warmblood fragile foal syndrome type 1 (WFFS), a fatal recessive defect of the connective tissue. Screening of multiple horse breeds identified the presence of the WFFS allele in the Thoroughbred. PLOD1 is involved in cross-linking of collagen fibrils and thus could potentially increase the risk of catastrophic breakdown.ObjectivesEstimate the frequency of the WFFS allele (PLOD1 c.2032G>A) and determine if it is a risk factor for catastrophic breakdown in the Thoroughbred.Study designCase-control genetic study.MethodsGenomic DNA from hair and/or tissue samples was genotyped for the WFFS allele. Fisher's Exact tests were performed to compare allele and carrier frequencies between the case cohort (catastrophic breakdown, n = 22) and several cohorts with no record of injury (n = 138 raced/trained at same track and season and n = 185 older than 7 years and raced during same season), nonracers (n = 92), and a random sample without consideration for racing history (n = 279).ResultsThe frequency of the PLOD1 c.2032G>A variant in the Thoroughbred breed is low (1.2%). Seventeen of 716 Thoroughbreds tested were carriers (2.4%) and no WFFS homozygotes were detected. Only one catastrophic breakdown case carried the WFFS allele. No statistically significant difference in allele or carrier frequency was identified between case and control cohorts (P>0.05 in all comparisons performed).Main limitationsThis study evaluated cases from one single track.ConclusionsThis study demonstrated that the PLOD1 c.2032G>A associated with WFFS is present at very low frequency in Thoroughbreds and is not a genetic risk factor for catastrophic breakdown

The Hindered M1 Radiative Decay Υ(2S) → ηb(1S)γ from Lattice NRQCD

We present a calculation of the hindered M$1$ $\Upsilon(2S) \to \eta_b(1S) \gamma$ decay rate using lattice non-relativistic QCD. The calculation includes spin-dependent relativistic corrections to the NRQCD action through $\mathcal{O}(v^6)$ in the quark's relative velocity, relativistic corrections to the leading order current which mediates the transition through the quark's magnetic moment, radiative corrections to the leading spin-magnetic coupling and for the first time a full error budget. We also use gluon field ensembles at multiple lattice spacing values, all of which include $u$, $d$, $s$ and $c$ quark vacuum polarisation. Our result for the branching fraction is $\mathcal{B}(\Upsilon(2S)\to\eta_b(1S)\gamma) = 5.4(1.8)\times 10^{-4}$, which agrees with the current experimental value.This is the author accepted manuscript. The final version is available from APS via http://dx.doi.org/10.1103/PhysRevD.92.09450

Improving the kinetic couplings in lattice nonrelativistic QCD

We improve the non-relativistic QCD (NRQCD) action by comparing the dispersion relation to that of the continuum through $\mathcal{O}(p^6)$ in perturbation theory. The one-loop matching coefficients of the $\mathcal{O}(p^4)$ kinetic operators are determined, as well as the scale at which to evaluate $\alpha_s$ in the $V$-scheme for each quantity. We utilise automated lattice perturbation theory using twisted boundary conditions as an infrared regulator. The one-loop radiative corrections to the mass renormalisation, zero-point energy and overall energy-shift of an NRQCD $b$-quark are also found. We also explore how a Fat$3$-smeared NRQCD action and changes of the stability parameter $n$ affect the coefficients. Finally, we use gluon field ensembles at multiple lattice spacing values, all of which include $u$, $d$, $s$ and $c$ quark vacuum polarisation, to test how the improvements affect the non-perturbatively determined $\Upsilon(1S)$ and $\eta_b(1S)$ kinetic masses, and the tuning of the $b$ quark mass

LC_2 formulation of supergravity

We formulate (N=1, d=11) supergravity in components in light-cone gauge (LC_2) to order $\kappa$. In this formulation, we use judicious gauge choices and the associated constraint relations to express the metric, three-form and gravitino entirely in terms of the physical degrees of freedom in the theory.Comment: 11 page

Reliability of Addenbrooke's Cognitive Examination III in differentiating between dementia, mild cognitive impairment and older adults who have not reported cognitive problems.

Diagnosing dementia can be challenging for clinicians, given the array of factors that contribute to changes in cognitive function. The Addenbrooke’s Cognitive Examination III (ACE-III) is commonly used in dementia assessments, covering the domains of attention, memory, fluency, visuospatial and language. This study aims to (1) assess the reliability of ACE-III to differentiate between dementia, mild cognitive impairment (MCI) and controls and (2) establish whether the ACE-III is useful for diagnosing dementia subtypes. Client records from the Northern Health and Social Care Trust (NHSCT) Memory Service (n = 2,331, 2013–2019) were used in the analysis including people diagnosed with Alzheimer’s disease (n = 637), vascular dementia (n = 252), mixed dementia (n = 490), MCI (n = 920) and controls (n = 32). There were significant differences in total ACE-III and subdomain scores between people with dementia, MCI and controls (p  73%) and thus the differences are not clinically relevant. The results suggest that ACE-III is a useful tool for discriminating between dementia, MCI and controls, but it is not reliable for discriminating between dementia subtypes. Nonetheless, the ACE-III is still a reliable tool for clinicians that can assist in making a dementia diagnosis in combination with other factors at assessment

High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland

Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (θsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/θ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role

Boundaries of Semantic Distraction: Dominance and Lexicality Act at Retrieval

Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category-exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1) and occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech is discussed

Randomized controlled trial of a good practice approach to treatment of childhood obesity in Malaysia: Malaysian childhood obesity treatment trial (MASCOT)

Context. Few randomized controlled trials (RCTs) of interventions for the treatment of childhood obesity have taken place outside the Western world. Aim. To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur, Malaysia. Methods. Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds. The intervention was relatively low intensity (8 hours contact over 26 weeks, group based), aiming to change child sedentary behavior, physical activity, and diet using behavior change counselling. Outcomes were measured at baseline and six months after the start of the intervention. Primary outcome was BMI z-score, other outcomes were weight change, health-related quality of life (Peds QL), objectively measured physical activity and sedentary behavior (Actigraph accelerometry over 5 days). Results. The intervention had no significant effect on BMI z score relative to control. Weight gain was reduced significantly in the intervention group compared to the control group (+1.5 kg vs. +3.5 kg, respectively, t-test p < 0.01). Changes in health-related quality of life and objectively measured physical activity and sedentary behavior favored the intervention group. Conclusions. Treatment was associated with reduced rate of weight gain, and improvements in physical activity and quality of life. More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes

Neonatal brain-directed gene therapy rescues a mouse model of neurodegenerative CLN6 Batten disease

The neuronal ceroid lipofuscinoses (NCLs), more commonly referred to as Batten disease, are a group of inherited lysosomal storage disorders that present with neurodegeneration, loss of vision and premature death. There are at least 13 genetically distinct forms of NCL. Enzyme replacement therapies and pre-clinical studies on gene supplementation have shown promising results for NCLs caused by lysosomal enzyme deficiencies. The development of gene therapies targeting the brain for NCLs caused by defects in transmembrane proteins has been more challenging and only limited therapeutic effects in animal models have been achieved so far. Here, we describe the development of an adeno-associated virus (AAV)-mediated gene therapy to treat the neurodegeneration in a mouse model of CLN6 disease, a form of NCL with a deficiency in the membrane-bound protein CLN6. We show that neonatal bilateral intracerebroventricular injections with AAV9 carrying CLN6 increase lifespan by more than 90%, maintain motor skills and motor coordination and reduce neuropathological hallmarks of Cln6-deficient mice up to 23 months post vector administration. These data demonstrate that brain-directed gene therapy is a valid strategy to treat the neurodegeneration of CLN6 disease and may be applied to other forms of NCL caused by transmembrane protein deficiencies in the future