Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

Background Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. Methods We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Results Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB’s atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Conclusions Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed

Vitamin a Deficiency in an Elderly Patient: A Diagnostic Challenge in the Age of AMD

Jakob M Pericak,1,2 Eric K Chin,3,4 David RP Almeida2 1State University of New York at Geneseo, Geneseo, NY, USA; 2Erie Retina Research & Center for Advanced Surgical Exploration, Erie, PA, USA; 3Retina Consultants of Southern California, Redlands, CA, USA; 4Loma Linda Eye Institute; Veterans Affair Hospital, Loma Linda, CA, USACorrespondence: David RP Almeida, Erie Retina Research & Center for Advanced Surgical Exploration, 300 State Street, Suite 302, Erie, PA, 16507, USA, Tel +1 814 476 6227, Fax +1 888 422 5096, Email [email protected]: The presentation of vitamin A deficiency (VAD)-induced ocular complications can be challenging to diagnose in elderly patients, particularly due to the overlap with age-related macular degeneration (AMD) symptoms. This case report details the presentation, diagnosis, and management of an 88-year-old female with vision loss, highlighting the ocular manifestations of presumed VAD. Despite vitamin A levels being at the lower end of the normal range, the patient’s symptoms and spectral domain optical coherence tomography (SD-OCT) findings suggested insufficient levels, leading to thinning of the outer nuclear layer. This case underscores the necessity of considering VAD in differential diagnoses of unexplained vision impairment, particularly in individuals with a history of intestinal malabsorption, while also emphasizing the importance of distinguishing VAD from AMD in elderly patients.Keywords: vitamin A deficiency, malabsorption syndrome, age-related macular degeneratio

Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

Early SUSVIMO in Neovascular Age-Related Macular Degeneration: Real Word Case Report and Clinical Implications

Jakob Pericak,1,2 Eric K Chin,3,4 David RP Almeida2 1State University of New York at Geneseo, Geneseo, NY, USA; 2Erie Retina Research & Center for Advanced Surgical Exploration, Erie, PA, USA; 3Retina Consultants of Southern California, Redlands, CA, USA; 4Loma Linda Eye Institute; Veterans Affair Hospital, Loma Linda, CA, USACorrespondence: David RP Almeida, Erie Retina Research & Center for Advanced Surgical Exploration, 300 State Street, Suite 302, Erie, PA, 16507, USA, Tel +1 814.476.6227, Fax +1 888.422.5096, Email [email protected]: The current standard of care for neovascular age-related macular degeneration is serial vascular endothelial growth factor (VEGF) inhibitor intravitreal injections at varying treatment intervals. SUSVIMO is a port-delivery system of ranibizumab that serves as an alternative, lower-maintenance treatment.Methods: A case report from a retinal surgery clinic describing the ocular findings, diagnostic workup, and alternative treatment for an 80-year-old man presenting with new-onset neovascular age-related macular degeneration.Results: Resolved foveal thickness, macular volume, and subretinal fluid after SUSVIMO implantation OD. The patient showed a better response to SUSVIMO than to previous anti-VEGF injections. Before the first refill, the patient began to experience subretinal fluid; however, it was resolved after the refill.Conclusion: Although effective, real-world management of neovascular age-related macular degeneration is associated with an extensive treatment burden that can compromise treatment adherence. Herein, we describe how the port delivery system (PDS; SUSVIMO) - a refillable ocular implant that can continuously deliver a novel formulation of ranibizumab with refills possible at six months or longer - is a viable early therapy that mitigates the treatment burden of intravitreal injections.Keywords: neovascular age-related macular degeneration, SUSVIMO, port delivery syste

The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population

The c.G4883C variant in the leucine-rich repeat kinase 2 (LRRK2) gene (protein effect: Arg1628Pro) has been recently proposed as a second risk factor for sporadic Parkinson's disease in the Han Chinese population (after the Gly2385Arg variant). In this paper, we analyze the Arg1628Pro variant and the associated haplotype in a large sample of 1,337 Han subjects (834 patients and 543 controls) ascertained from a single referral center in Taiwan. In our sample, the Arg1628Pro allele was more frequent among patients (3.8%) than among controls (1.8%; p = 0.004, OR 2.13, 95% CI 1.29-3.52). Sixty heterozygous and two homozygous carriers of the Arg1628Pro variant were identified among the patients, of which only one was also a carrier of the LRRK2 Gly2385Arg variant. We also show that carriers of the Arg1628Pro variant share a common, extended haplotype, suggesting a founder effect. Parkinson's disease onset age was similar in patients who carried the Arg1628Pro variant and in those who did not carry it. Our data support the contention that the Arg1628Pro variant is a second risk factor for Parkinson's disease in the Han Chinese population. Adding the estimated effects of Arg1628Pro (population attributable risk [PAR] ∼4%) and Gly2385Arg variants (PAR ∼6%) yields a total PAR of ∼10%

The effect of incorrect scanning distance on boundary detection errors and macular thickness measurements by spectral domain optical coherence tomography: a cross sectional study

BACKGROUND: To investigate the influence of scan distance on retinal boundary detection errors (RBDEs) and retinal thickness measurements by spectral domain optical coherence tomography (SD-OCT). METHODS: 10 eyes of healthy subjects, 10 eyes with diabetic macular edema (DME) and 10 eyes with neovascular age-related macular degeneration (AMD) were examined with RTVue SD-OCT. The MM5 protocol was used in two consecutive sessions to scan the macula. For the first session, the device was set 3.5 cm from the eye in order to obtain detectable signal with low fundus image quality (suboptimal setting) while in the second session a distance of 2.5 cm was set with a good quality fundus image. The signal strength (SSI) value was recorded. The score for retinal boundary detection errors (RBDE) was calculated for ten scans of each examination. RBDE scores were recorded for the whole scan and also for the peripheral 1.0 mm region. RBDE scores, regional retinal thickness values and SSI values between the two sessions were compared. The correlation between SSI and the number of RBDEs was also examined. RESULTS: The SSI was significantly lower with suboptimal settings compared to optimal settings (63.9+/-12.0 vs. 68.3+/-12.2, respectively, p = 0.001) and the number of RBDEs was significantly higher with suboptimal settings in the "all-eyes" group along with the group of healthy subjects and eyes with DME (9.1+/-6.5 vs. 6.8+/-6.3, p = 0.007; 4.4+/-2.6 vs. 2.5+/-1.6, p = 0.035 and 9.7+/-3.3 vs. 5.1+/-3.7, p = 0.008, respectively). For these groups, significant negative correlation was found between the SSI and the number of RBDEs. In the AMD group, the number of RBDEs was markedly higher compared to the other groups and there was no difference in RBDEs between optimal and suboptimal settings with the errors being independent of the SSI. There were significantly less peripheral RBDEs with optimal settings in the "all-eyes" group and the DME subgroup (2.7+/-2.6 vs. 4.2+/-2.8, p = 0.001 and 1.4+/-1.7 vs. 4.1+/-2.2, p = 0.007, respectively). Retinal thickness in the two settings was significantly different only in the outer-superior region in DME. CONCLUSIONS: Optimal distance settings improve SD-OCT SSI with a decrease in RBDEs while retinal thickness measurements are independent of scanning distance

The pattern of breeding and management within the New Zealand Thoroughbred breeding industry 2005-2015. (II) The mare population

Context: The New Zealand Thoroughbred breeding industry is heavily focused on producing horses for the export market and there has been a reduction in the number of horses racing in the past 20 years. The impact of these production constraints, and changes in production focus, have not been described at a national herd level. Aim: To describe the breeding management, reproductive performance, and careers of the New Zealand Thoroughbred broodmare herd during the 2005/06-2015/16 breeding seasons. Methods: The demographics, population structure, reproductive efficiency, breeding management and career descriptors of Thoroughbred mares were examined using descriptive analysis. Gestation length was modelled using a linear mixed effects model. The impact of different variables on breeding career were quantified by calculating odds ratio. Results: There was a consistent reduction in the size of the national broodmare herd over the 10 years investigated. Half of the mares not retained for breeding were mares that were breed to low-cost stallions. Despite a short (∼100 days) commercial breeding season few (20%) mares were mated early in the season (September), with most mating (70%) occurring between October and November. The 27 days mean foaling to conception interval (FCI) suggests that FCI was artificially shortened and most pregnancy was achieved within first oestrus cycle post-partum. Mare career length and lifetime productivity was positively associated with the stud fee of the first stallion that the mare was mated to and number of foals registered for racing. Conclusion: Mare replacement and loss within the national herd was disproportionately associated with mares that were producing foals for a contracting domestic racing market. There was a constricted breeding season with most mares being mated within the first oestrous cycle post-partum. Mare retention and breeding success were positively associated with the service fee of the sire and progeny that had raced, reflecting the commercial pressure of the industry on mare management. Implication: The changes in the broodmare herd and management reflects the increasing proportion of the industry focusing on breeding foals that will appeal to the export market. The economic drivers for early born foals provide management challenges as these are not aligned with the optimal reproductive season of the horse.fals

Career profile and pattern of racing for Thoroughbred jumps-racing horses in New Zealand

Context Racing structure and focus for racehorses differs across jurisdictions and is poorly described. In New Zealand and Australia, jumps racing accounts for a small proportion of total Thoroughbred races each year, as opposed to the larger jumps-racing (National Hunt) industry with purpose-bred horses found in the UK and Ireland. Aims This study aimed to describe the career profile and pattern of racing for Thoroughbred jumps-racing horses in New Zealand. Methods Metrics from every horse with a full jumps-racing career (n = 1276, 89% geldings) between the 2005/06 and 2021/22 racing seasons (n = 40,302 starts) were examined. Descriptive statistics, box plots and heat maps were used to describe the data, by using horse age as a proxy for career progression. Key results Jumps-racing horses had a median of 17 flat starts (IQR 9–30) before their first jumps-racing start. The median career of a jumps-racing horse was 3.7 years (IQR 2.3–5.2) and 29 starts (IQR 16–44). Older horses had a decreasing number of flat-racing starts and an increasing proportion of steeplechase-racing starts. However, the majority of horses still had at least one flat-race start per calendar year, often prior to the first jumps race. Most horses had one spell each season (length 194 days, IQR 124–259), and a condensed preparation length over the winter months, with a median of 14 days (IQR 10–21) between starts. Conclusion The career pattern for jumps-racing horses in New Zealand reflects the industry retention of horses with a prior career in flat racing into a secondary jumps-racing career. Successful horses have increased focus on preparation for the winter jumps-racing season. Implications Jumps racing provides a secondary racing career for some flat-racing horses, particularly geldings. This strategy reduces wastage of horses from the industry.fals

Physical Fitness of Thoroughbred Horse Racing Jockeys

Purpose Thoroughbred racing jockeys compete at maximum physiological capacity in a sport with a high risk of falls and injury. A greater understanding of the physical capacities determining jockey performance may lead to minimum physical performance parameters and corrective interventions to improve jockey fitness and performance and reduce jockey and horse injury. The aim of this study was to develop appropriate physical testing procedures for jockeys and a physical fitness profile for different licence levels. Methods Fifty-eight jockeys (n = 24 females, n = 34 males), representing all apprentice jockeys licenced in New Zealand in 2021 (100%, n = 8 probationers and n = 39 apprentices) and eleven professional jockeys (14%) were assessed to determine baseline physiological and fitness data. Descriptive statistics and boxplots were used to compare aerobic fitness, abdominal (core), upper and lower body strength, muscular power, reaction time, flexibility and a novel ‘saddle’ test targeting lower body strength, balance, and endurance between licencing levels. Effect Size (ES) was used to determine magnitude of differences between groups. Results More experienced jockeys had greater relative lower body strength (ES = 0.2–0.7) and better balance (ES = 0.5–0.9) compared to the less experienced groups. Jockeys who were in the top 20 of the premiership table (jockey rankings) had faster reaction times (ES = 0.7) and greater core extensor strength (ES = 0.7) than other cohorts. Most tests showed little differentiation between jockey licence levels, however the ‘saddle test’ showed greater variability in the less experienced race riders. This test may be an effective measure of jockey baseline performance. Conclusions These data could be used to inform minimum jockey licencing requirements and future physical fitness training programmes to increase jockey physiological fitness, thereby minimising risk of falls or injury due to physiological deficits and performance.fals

Quantification of relative stock units for horses to permit correct application within pasture-based production systems

Context. Overseer® is the primary software tool used to estimate farm-level nutrient cycle and management for regulatory purposes in New Zealand. The model compares feed demand among different livestock by using ‘revised stock units’ (RSUs, the annual energy requirement of a mature ewe to raise a single lamb to weaning; 6000 MJ metabolisable energy). The RSUs for several common equine stock classes are not yet available, while those currently available within the model are based on the linear scaling of feed demand to liveweight, which does not consider allometric scaling of metabolism to liveweight or the differences in digestive physiology and nutrient metabolism between ruminants and monogastric hindgut fermenters (horses). Aim. To compare the current RSU values used in Overseer® for different equine stock classes, with the equineRSU values calculated using equine-specific models. Methods. Weighted average estimates of the bodyweight for the different equine livestock classes were calculated from the published literature. These weighted average estimates of bodyweight were used to estimate the energy requirements on the basis of data published by National Research Council. The resulting dry-matter intake and N intake from the equineRSU values and the current RSU values in use within Overseer® were modelled using published data on diet composition, crude protein content and the digestibility of the different feeds offered. Results. The current RSUs in Overseer were 2.5–6.8 units higher than the equineRSU values obtained from the equine-specific models. This overestimation in feed demand resulted in N-intake estimates at an animal level being 52–108% higher than values derived using the equine-specific estimates. Conclusion. The use of RSUs based on linear scaling of feed demand from ruminants on the basis of liveweight overestimates feed demand and N intake in horses. If horses are to be included within nutrient management models, feed demand must be based on published equine data for energy requirements to avoid over-inflation of N excretion. The equineRSUs calculated in this study reduce the risk of over-inflation of N intake and excretion, and subsequently the N leaching estimations. Implication. Failure to accurately model feed demand of horses within nutrient management software would unfairly compromise stocking density and horse management on large commercial breeding farms. The implication for these errors on economic impact and restricted livestock number is greatest for the Thoroughbred breeding industry due to the scale of the operations.fals