Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure disorder that often presents at infancy. Progress has been made in revealing causal mutated genes (SBDS and others), ribosome defects, and hematopoietic aberrations in SDS. However, the mechanism underlying the hematopoietic failure remained unknown, and treatment options are limited. Herein, we investigated the onset of SDS embryonic hematopoietic impairments. We generated SDS and control human-derived induced pluripotent stem cells (iPSCs). SDS iPSCs recapitulated the SDS hematological phenotype. Detailed stepwise evaluation of definitive hematopoiesis revealed defects that started at the early emerging hematopoietic progenitor (EHP) stage after mesoderm and hemogenic endothelium were normally induced. Hematopoietic potential of EHPs was markedly reduced, and the introduction of SBDS in SDS iPSCs improved colony formation. Transcriptome analysis revealed reduced expression of ribosome and oxidative phosphorylation-related genes in undifferentiated and differentiated iPSCs. However, certain pathways (e.g., DNA replication) and genes (e.g., CHCHD2) were exclusively or more severely dysregulated in EHPs compared with earlier and later stages. To our knowledge, this study offers for the first time an insight into the embryonic onset of human hematopoietic defects in an inherited bone marrow failure syndrome and reveals cellular and molecular aberrations at critical stages of hematopoietic development toward EHPs.

Anaesthesia associates' clinical activity, case mix, supervision and involvement in peri-operative cardiac arrest: analysis from the 7th National Audit Project.

BACKGROUND: We analysed the clinical practice of anaesthesia associates in the UK, as reported to the 7th National Audit Project of the Royal College of Anaesthetists, and compared these with medically qualified anaesthetists. METHODS: We included data from our baseline survey, activity survey and case registry as with other reports from the project. RESULTS: Among 197 departments of anaesthesia, 52 (26%) employed anaesthesia associates. Of 10,009 responding anaesthesia care providers, 71 (< 1%) were anaesthesia associates, of whom 33 (47%) reporting working nights or weekends (compared with 97% of medically qualified anaesthetists in training and > 90% of consultants). Anaesthesia associates reported less training and confidence in managing peri-operative cardiac arrest and its aftermath compared with medically qualified anaesthetists. Anaesthesia associates were less directly involved in the management and the aftermath of peri-operative cardiac arrest than medically qualified anaesthetists, and the psychological impacts on professional and personal life appeared to be less. Among 24,172 cases, anaesthesia associates attended 432 (2%) and were the senior anaesthesia care provider in 63 (< 1%), with indirect supervision in 27 (43%). Anaesthesia associates worked predominantly in a small number of surgical specialties during weekdays and working daytime hours. Complication rates were low in cases managed by anaesthesia associates, likely reflecting case mix. However, activity and registry case mix data show anaesthesia associates do manage high-risk cases (patients who are older, comorbid, obese and frail) with the potential for serious complications. Registry cases included higher risk cases with respect to the clinical setting and patient factors. CONCLUSION: Anaesthesia associates work in enhanced roles, relative to the scope of practice at qualification agreed by organisations. Recent changes mean the Royal College of Anaesthetists and Association of Anaesthetists do not currently support an enhanced scope of practice.

Advanced life support interventions during intra-operative cardiac arrest among adults as reported to the 7th National Audit Project of the Royal College of Anaesthetists.

BACKGROUND: Few existing resuscitation guidelines include specific reference to intra-operative cardiac arrest, but its optimal treatment is likely to require some adaptation of standard protocols. METHODS: We analysed data from the 7th National Audit Project of the Royal College of Anaesthetists to determine the incidence and outcome from intra-operative cardiac arrest and to summarise the advanced life support interventions reported as being used by anaesthetists. RESULTS: In the baseline survey, > 50% of anaesthetists responded that they would start chest compressions when the non-invasive systolic pressure was < 40-50 mmHg. Of the 881 registry patients, 548 were adult patients (aged > 18 years) having non-obstetric procedures under the care of an anaesthetist, and who had arrested during anaesthesia (from induction to emergence). Sustained return of spontaneous circulation was achieved in 425 (78%) patients and 338 (62%) were alive at the time of reporting. In the 365 patients with pulseless electrical activity or bradycardia, adrenaline was given as a 1 mg bolus in 237 (65%). A precordial thump was used in 14 (3%) patients, and although this was associated with return of spontaneous circulation at the next rhythm check in almost three-quarters of patients, in only one of these was the initial rhythm shockable. Calcium (gluconate or chloride) and 8.4% sodium bicarbonate were given to 51 (9%) and 25 (5%) patients, but there were specific indications for these treatments in less than half of the patients. A thrombolytic drug was given to 5 (1%) patients, and extracorporeal cardiopulmonary resuscitation was used in 9 (2%) of which eight occurred during cardiac procedures. CONCLUSIONS: The specific characteristics of intra-operative cardiac arrest imply that its optimal treatment requires modifications to standard advanced life support guidelines.

Periprosthetic Joint Infection After Total Knee Arthroplasty With or Without Antibiotic Bone Cement.

Importance: Despite increased use of antibiotic-loaded bone cement (ALBC) in joint arthroplasty over recent decades, current evidence for prophylactic use of ALBC to reduce risk of periprosthetic joint infection (PJI) is insufficient. Objective: To compare the rate of revision attributed to PJI following primary total knee arthroplasty (TKA) using ALBC vs plain bone cement. Design, Setting, and Participants: This international cohort study used data from 14 national or regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, New Zealand, Norway, Romania, Sweden, Switzerland, the Netherlands, the UK, and the US. The study included primary TKAs for osteoarthritis registered from January 1, 2010, to December 31, 2020, and followed-up until December 31, 2021. Data analysis was performed from April to September 2023. Exposure: Primary TKA with ALBC vs plain bone cement. Main Outcomes and Measures: The primary outcome was risk of 1-year revision for PJI. Using a distributed data network analysis method, data were harmonized, and a cumulative revision rate was calculated (1 - Kaplan-Meier), and Cox regression analyses were performed within the 10 registries using both cement types. A meta-analysis was then performed to combine all aggregated data and evaluate the risk of 1-year revision for PJI and all causes. Results: Among 2 168 924 TKAs included, 93% were performed with ALBC. Most TKAs were performed in female patients (59.5%) and patients aged 65 to 74 years (39.9%), fully cemented (92.2%), and in the 2015 to 2020 period (62.5%). All participating registries reported a cumulative 1-year revision rate for PJI of less than 1% following primary TKA with ALBC (range, 0.21%-0.80%) and with plain bone cement (range, 0.23%-0.70%). The meta-analyses based on adjusted Cox regression for 1 917 190 TKAs showed no statistically significant difference at 1 year in risk of revision for PJI (hazard rate ratio, 1.16; 95% CI, 0.89-1.52) or for all causes (hazard rate ratio, 1.12; 95% CI, 0.89-1.40) among TKAs performed with ALBC vs plain bone cement. Conclusions and Relevance: In this study, the risk of revision for PJI was similar between ALBC and plain bone cement following primary TKA. Any additional costs of ALBC and its relative value in reducing revision risk should be considered in the context of the overall health care delivery system.

Subthalamic nucleus shows opposite functional connectivity pattern in Huntington's and Parkinson's disease.

Huntington's and Parkinson's disease are two movement disorders representing mainly opposite states of the basal ganglia inhibitory function. Despite being an integral part of the cortico-subcortico-cortical circuitry, the subthalamic nucleus function has been studied at the level of detail required to isolate its signal only through invasive studies in Huntington's and Parkinson's disease. Here, we tested whether the subthalamic nucleus exhibited opposite functional signatures in early Huntington's and Parkinson's disease. We included both movement disorders in the same whole-brain imaging study, and leveraged ultra-high-field 7T MRI to achieve the very fine resolution needed to investigate the smallest of the basal ganglia nuclei. Eleven of the 12 Huntington's disease carriers were recruited at a premanifest stage, while 16 of the 18 Parkinson's disease patients only exhibited unilateral motor symptoms (15 were at Stage I of Hoehn and Yahr off medication). Our group comparison interaction analyses, including 24 healthy controls, revealed a differential effect of Huntington's and Parkinson's disease on the functional connectivity at rest of the subthalamic nucleus within the sensorimotor network, i.e. an opposite effect compared with their respective age-matched healthy control groups. This differential impact in the subthalamic nucleus included an area precisely corresponding to the deep brain stimulation 'sweet spot'-the area with maximum overall efficacy-in Parkinson's disease. Importantly, the severity of deviation away from controls' resting-state values in the subthalamic nucleus was associated with the severity of motor and cognitive symptoms in both diseases, despite functional connectivity going in opposite directions in each disorder. We also observed an altered, opposite impact of Huntington's and Parkinson's disease on functional connectivity within the sensorimotor cortex, once again with relevant associations with clinical symptoms. The high resolution offered by the 7T scanner has thus made it possible to explore the complex interplay between the disease effects and their contribution on the subthalamic nucleus, and sensorimotor cortex. Taken altogether, these findings reveal for the first time non-invasively in humans a differential, clinically meaningful impact of the pathophysiological process of these two movement disorders on the overall sensorimotor functional connection of the subthalamic nucleus and sensorimotor cortex.

The use of antibiotic-loaded bone cement and systemic antibiotic prophylactic use in 2,971,357 primary total knee arthroplasties from 2010 to 2020: an international register-based observational study among countries in Africa, Europe, North America, and Oceania.

BACKGROUND AND PURPOSE: Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). PATIENTS AND METHODS: This observational study is based on 2,971,357 primary TKAs reported in 2010-2020 to national/regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA. Aggregate-level data on trends and types of bone cement, antibiotic agents, and doses and duration of SAP used was extracted from participating registries. RESULTS: ALBC was used in 77% of the TKAs with variation ranging from 100% in Norway to 31% in the USA. Palacos R+G was the most common (62%) ALBC type used. The primary antibiotic used in ALBC was gentamicin (94%). Use of ALBC in combination with SAP was common practice (77%). Cefazolin was the most common (32%) SAP agent. The doses and duration of SAP used varied from one single preoperative dosage as standard practice in Bolzano, Italy (98%) to 1-day 4 doses in Norway (83% of the 40,709 TKAs reported to the Norwegian arthroplasty register). CONCLUSION: The proportion of ALBC usage in primary TKA varies internationally, with gentamicin being the most common antibiotic. ALBC in combination with SAP was common practice, with cefazolin the most common SAP agent. The type of ALBC and type, dose, and duration of SAP varied among participating countries.

Does melatonin administration reduce the incidence of postoperative delirium in adults? Systematic review and meta-analysis.

Postoperative delirium (POD) is common. It is associated with increased morbidity and mortality. Many cases may be preventable and melatonin offers promise as a preventative agent. OBJECTIVE: This systematic review provides an up-to-date synthesis of the evidence on the effect of melatonin in preventing POD. DESIGN: A systematic search of randomised controlled trials of melatonin in POD was run across multiple databases (EMBASE, MEDLINE, CINAHL, PsycINFO) and a clinical trials registry (ClinicalTrials.org) (1 January 1990 to 5 April 2022). Studies examining the effects of melatonin on POD incidence in adults are included. Risk of bias was assessed using the Cochrane risk of bias 2 tool. OUTCOME MEASURES: The primary outcome is POD incidence. Secondary outcomes are POD duration and length of hospital stay. Data synthesis was undertaken using a random-effects meta-analysis and presented using forest plots. A summary of methodology and outcome measures in included studies is also presented. RESULTS: Eleven studies, with 1244 patients from a range of surgical specialties were included. Seven studies used melatonin, in variable doses, and four used ramelteon. Eight different diagnostic tools were used to diagnose POD. Time points for assessment also varied. Six studies were assessed as low risk of bias and five as some concern. The combined OR of developing POD in the melatonin groups versus control was 0.41 (95% CI 0.21 to 0.80, p=0.01). CONCLUSION: This review found that melatonin may reduce the incidence of POD in adults undergoing surgery. However, included studies displayed inconsistency in their methodology and outcome reporting. Further work to determine the optimum regime for melatonin administration, along with consensus of how best to evaluate results, would be beneficial. PROSPERO REGISTRATION NUMBER: CRD42021285019.

The Differential Contribution of Macular Pigments and Foveal Anatomy to the Perception of Maxwell's Spot and Haidinger's Brushes.

The relationship of macular pigments and foveal anatomy to the perception of Maxwell's spot (MS) and Haidinger's brushes (HB) entoptic phenomena were investigated. Dual-wavelength-autofluorescence and OCT were used to define macular pigment density and foveal anatomy in 52 eyes. MS was generated by alternating unpolarized red/blue and red/green uniform field illumination. HB was generated by alternating the linear polarization axis of a uniform blue field. In Experiment 1, horizontal widths of MS and HB were measured using a micrometer system and compared with macular pigment densities and OCT-defined morphometry. MS radius (mean 1.4°) was significantly less than HB radius (mean 1.6°), with the spatial extent of both phenomena falling between the boundaries of the foveola and foveal pit. Multiple regression showed MS and HB radii to be significantly associated with the macular pigment spatial profile radius. HB radius, but not MS radius, was also significantly associated with foveolar morphometry. Experiment 2 compared perceptual profiles of MS with macular pigment distribution patterns and demonstrated close agreement. The size and appearance of MS is a direct indicator of macular pigment density and distribution. Measures of HB radii are less specific, with dependence on both macular pigment density and foveal structure.

Intravascular lithotripsy-assisted PCI for severely calcified coronary lesions: evaluating the impact on quality of life and outcomes.

BACKGROUND: Despite the increased uptake of intravascular lithotripsy (IVL) for treating severely calcified coronary lesions, there is limited patient-level data examining the effect of IVL on quality of life, symptomatology, and outcomes beyond 30 days. We sought to assess demographics, procedural characteristics, outcomes, and impact of IVL on patient-reported angina after a minimum of 6 months follow-up. METHODS: A retrospective single-center study was conducted of patients treated with coronary IVL between January and October 2020. Baseline demographics were obtained from electronic patient records and SYNTAX scores were calculated from index coronary angiograms. Technical success and complications were assessed along with clinical outcomes, which included all-cause mortality, myocardial infarction (MI), target lesion revascularization (TLR), and MACE (composite of death, stroke, MI, and TLR). Canadian Cardiovascular Society (CCS) angina classification was assessed at virtual clinical follow-up. RESULTS: Forty-seven consecutive patients were included. At a mean follow-up of 306 ± 74 days, the mean CCS angina score was reduced by 53% post-IVL-assisted PCI (2.9 vs 1.4, p < 0.001). Technical and procedural success were high (94% and 92%, respectively). One patient (2%) met the pre-specified criteria for in-hospital MACE and 4 (9%) met pre-specified MACE at follow-up, including 2 deaths and 2 TLR. Procedural complications included coronary dissection (11%) and coronary perforation (6%) and were managed either conservatively or with PCI. CONCLUSIONS: Coronary IVL is a safe and effective adjunctive therapy for treating heavily calcified coronary lesions. This cohort shows high procedural success and a significant reduction in CCS angina at follow-up.

An investigation of movement dynamics and muscle activity during traditional and accentuated-eccentric squatting.

INTRODUCTION: Accentuated-eccentric loading (AEL) takes advantage of the high force producing potential of eccentric muscle contractions, potentially maximising mechanical tension within the muscle. However, evidence is lacking on how AEL squatting may load the involved musculature, limiting scientifically justified programming recommendations. The purpose of this study was to investigate the effects of concentric and eccentric loads on joint loading and muscle activity of the lower limbs. METHODS: Resistance trained males performed traditional squatting (20-100% of concentric one-repetition maximum [1RM]) and AEL squatting with eccentric loads (110-150% of 1RM) provided by a novel motorised isotonic resistance machine (Kineo). Kinetics and kinematics of the hip, knee, and ankle joints were collected, with electromyography from the gluteus maximus, vastus lateralis, biceps femoris, and gastrocnemius medialis. A secondary cohort underwent a kinematic and electromyography analysis of squatting technique to compare Kineo and back and front barbell squatting. RESULTS: Knee joint peak eccentric moments occurred at 120% 1RM (P = 0.045), with no further increase thereafter. As eccentric load increased, the time course of moment development occurred earlier in the eccentric phase. This resulted in a 37% increase in eccentric knee extensor work from the 80% 1RM trial to the 120% 1RM trial (P<0.001). Neither hip nor ankle joints displayed further change in kinetics as eccentric load increased above 100% 1RM. Electromyographic activity during traditional squatting was ~15-30% lower in all eccentric trials than in concentric trials for all muscles. EMG plateaued between a load of 80-100% 1RM during the eccentric trials and did not increase with AEL. No significant differences in kinematics were found between Kineo and barbell squatting. CONCLUSIONS: The knee extensors appear to be preferentially loaded during AEL squatting. The greater work performed during the eccentric phase of the squat as eccentric load increased suggests greater total mechanical tension could be the cause of adaptations from AEL. Our data suggest that AEL should be programmed with a load of 120% of 1RM. Further studies are needed to confirm the longer-term training effects of AEL.

Implementing large-scale data quality validation in a national arthroplasty registry to improve compliance : the National Joint Registry data quality audit programme.

Data of high quality are critical for the meaningful interpretation of registry information. The National Joint Registry (NJR) was established in 2002 as the result of an unexpectedly high failure rate of a cemented total hip arthroplasty. The NJR began data collection in 2003. In this study we report on the outcomes following the establishment of a formal data quality (DQ) audit process within the NJR, within which each patient episode entry is validated against the hospital unit's Patient Administration System and vice-versa. This process enables bidirectional validation of every NJR entry and retrospective correction of any errors in the dataset. In 2014/15 baseline average compliance was 92.6% and this increased year-on-year with repeated audit cycles to 96.0% in 2018/19, with 76.4% of units achieving > 95% compliance. Following the closure of the audit cycle, an overall compliance rate of 97.9% was achieved for the 2018/19 period. An automated system was initiated in 2018 to reduce administrative burden and to integrate the DQ process into standard workflows. Our processes and quality improvement results demonstrate that DQ may be implemented successfully at national level, while minimizing the burden on hospitals.Cite this article: Bone Jt Open 2022;3(9):716-725.

Melatonin for the prevention of postoperative delirium in older adults: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Postoperative delirium (POD) is a major cause of morbidity, particularly in elderly patients. Melatonin has been suggested as a low-risk pharmacological intervention to help prevent POD. A previous systematic review found limited high-quality evidence to support the use of melatonin in the prevention of POD. Several further randomised studies have since been published. This systematic review aims to synthesise the evidence from randomised controlled trials (RCTs) examining the effect of melatonin on the prevention of POD in older adults. METHODS AND ANALYSIS: A systematic search of RCTs of melatonin (any dose and formulation) in POD will be run across Embase, Medline, CINAHL and PsychInfo. RCTs published from January 1990 until the end of February 2022 and reporting outcomes for melatonin use to prevent POD in patients will be included. Screening of search results and data extraction from included articles will be performed by two independent reviewers. The primary outcome will be incidence of POD in older adults undergoing surgery. Secondary outcomes are delirium duration and length of hospital stay. The review will also describe the dosage, timing and administration regimes of melatonin therapy and as well as the scales and definitions used to describe POD. A registry review of ongoing trials will be also be performed. For the meta-analysis, data will be pooled using a random effects model to generate a forest plot and obtain an odds ratio (OR) for the incidence of POD. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. ETHICS AND DISSEMINATION: No ethical approval is required. This review will be disseminated via peer-reviewed manuscript and conferences. The results will be used as the basis of work to optimise this intervention for future trials in surgical populations. PROSPERO REGISTRATION NUMBER: This review is registered with PROSPERO (CRD42021285019).

Investigating target refraction advice provided to cataract surgery patients by UK optometrists and ophthalmologists.

PURPOSE: To determine whether UK optometrists and ophthalmologists provide target refraction advice to patients prior to cataract surgery, and when this should first be discussed. METHODS: Optometrists and ophthalmologists were asked to complete a survey of two clinical vignettes (both older patients with cataract; a pre-operative myope who routinely read without glasses and a patient using a monovision approach), plus multiple choice and short answer questions either using hard copy or online. RESULTS: Responses were obtained from 437 optometrists and 50 ophthalmologists. Optometrists who reported they would provide target refraction advice were more experienced (median 22 years) than those who would leave this to the Hospital Eye Service (median 10 years). The former group reported it was in the patients' best interest to make an informed decision as they had seen many myopic patients who read uncorrected pre-operatively, and were unhappy that they could no longer do so after surgery. Inexperienced optometrists reported that they did not want to overstep their authority and left the decision to the ophthalmologist. The ophthalmologists estimated their percentage of emmetropic target refractions over the last year to have been 90%. CONCLUSION: Currently, some long-term myopes become dissatisfied after cataract surgery due to an emmetropic target refraction that leaves them unable to read without glasses as they did prior to surgery. Although experienced optometrists are aware of this and attempt to discuss this issue with patients, less experienced optometrists tend not to. This suggests that target refraction needs greater exposure in university training and continuing professional development. To provide patients with the knowledge to make informed decisions regarding their surgery, we suggest an agreed protocol within funded direct referral schemes of initial target refraction discussions by optometrists to introduce the idea of refractive outcomes and outline options, with further discussion with the ophthalmologist to clarify understanding.

Tear Film Surface Quality in Modern Daily Disposable Contact Lens Wear.

OBJECTIVES: As reported previously, tear film surface quality (TFSQ) should be considered in contact lens (CL) fitting. This study followed noninvasive keratograph tear film break-up time (NIKBUT) in CL wearers for 12 months to validate its clinical utility in predicting CL performance. METHODS: Fifty-five subjects (M/F=17/38) aged 26±4 years were prescribed silicone hydrogel or hydrogel CLs. The study included baseline measurements without CLs; 2 visits for CL fitting and control; follow-up after 3, 6, and 12 months of CL wear; and postwear visit without CLs. Ocular Surface Disease Index (OSDI), 8-Item Contact Lens Dry Eye Questionnaire (CLDEQ-8), first and mean NIKBUT (F/M-NIKBUT), fluorescein tear film break-up time (FBUT), and ocular surface staining were evaluated. RESULTS: Post hoc analysis of each pair of visits showed differences between baseline and all CL visits for F-NIKBUT, M-NIKBUT, FBUT, and corneal staining. No difference was reported in symptoms. In addition, differences between baseline and postwear visits were noted in OSDI, M-NIKBUT, FBUT, and corneal staining, with three of the latter parameters showing a downward trend. CONCLUSIONS: No changes in TFSQ and symptoms were reported over 12 months. Introducing NIKBUT as part of routine CL fitting is advised to improve CL fit and predict success.

Impaired autonomic function after incomplete revascularisation.

INTRODUCTION: Incomplete cardiac revascularisation (ICR) assessed by residual SYNTAX score (rSs) is associated with increased 5-year mortality. Furthermore, in the general population, our group has demonstrated that impaired autonomic function determined by heart rate recovery time between 10 and 20 s (HRR10-20) following an active stand is associated with increased all-cause mortality. PURPOSE: We hypothesised that ICR would be associated with impaired autonomic function determined by HRR10-20. METHODS: After ethical approval and informed consent, consecutive patients attending cardiac rehabilitation in a tertiary referral centre were enrolled. All patients had percutaneous coronary revascularisation. During an active stand, real-time heart rate, blood pressure and ECG recordings were taken using non-invasive digital photoplethysmography and HRR10-20 determined. Assessment of autonomic function was performed by determining speed of HRR10-20 post-orthostatic challenge.Patients with an rSs >0 were considered incompletely revascularised and those with an rSs of 0 fully revascularised. Demographic data were recorded and statistical analysis performed. RESULTS: Patients (n=53) comprised those with complete revascularisation (CR) (n=37) and ICR (n=16). In the ICR group, mean rSs was 9.4.HRR10-20 was impaired in the ICR group (-3±0.60) compared with the CR cohort (-6.56±0.52) (p<0.0001). Completeness of revascularisation was strongly associated with HRR10-20 (Pearson's correlation coefficient 0.529; p<0.0001). Baseline demographics did not differ significantly. Use of rate-limiting medication was similar between cohorts (beta blockers, calcium channel blockers, ivabradine). CONCLUSIONS: Our data confirm significant correlation between ICR and impaired autonomic function determined by speed of heart rate recovery. Thus, determining autonomic dysfunction post-ICR may identify those at increased mortality risk.

Biogeochemical processes create distinct isotopic fingerprints to track floodplain rearing of juvenile salmon.

Floodplains represent critical nursery habitats for a variety of fish species due to their highly productive food webs, yet few tools exist to quantify the extent to which these habitats contribute to ecosystem-level production. Here we conducted a large-scale field experiment to characterize differences in food web composition and stable isotopes (δ¹³C, δ¹5N, δ³4S) for salmon rearing on a large floodplain and adjacent river in the Central Valley, California, USA. The study covered variable hydrologic conditions including flooding (1999, 2017), average (2016), and drought (2012-2015). In addition, we determined incorporation rates and tissue fractionation between prey and muscle from fish held in enclosed locations (experimental fields, cages) at weekly intervals. Finally, we measured δ³4S in otoliths to test if these archival biominerals could be used to reconstruct floodplain use. Floodplain-reared salmon had a different diet composition and lower δ13C and δ³4S (δ¹³C = -33.02±2.66‰, δ³4S = -3.47±2.28‰; mean±1SD) compared to fish in the adjacent river (δ¹³C = -28.37±1.84‰, δ³4S = +2.23±2.25‰). These isotopic differences between habitats persisted across years of extreme droughts and floods. Despite the different diet composition, δ¹5N values from prey items on the floodplain (δ¹5N = 7.19±1.22‰) and river (δ¹5N = 7.25±1.46‰) were similar, suggesting similar trophic levels. The food web differences in δ13C and δ³4S between habitats were also reflected in salmon muscle tissue, reaching equilibrium between 24-30 days (2014, δ¹³C = -30.74±0.73‰, δ³4S = -4.6±0.68‰; 2016, δ¹³C = -34.74 ±0.49‰, δ³4S = -5.18±0.46‰). δ³4S measured in sequential growth bands in otoliths recorded a weekly time-series of shifting diet inputs, with the outermost layers recording time spent on the floodplain (δ³4S = -5.60±0.16‰) and river (δ³4S = 3.73±0.98‰). Our results suggest that δ¹³C and δ³4S can be used to differentiate floodplain and river rearing habitats used by native fishes, such as Chinook Salmon, across different hydrologic conditions and tissues. Together these stable isotope analyses provide a toolset to quantify the role of floodplains as fish habitats.

The Effect of Age-Related Macular Degeneration on Polarization Pattern Perception.

Purpose: The purpose of this study was to determine if a battery of polarization-modulated stimuli, quantified as a single metric, is effective in identifying macular disease in the presence/absence of cataract or pseudophakia. Methods: Using a modified liquid crystal display, polarization pattern perception (PPP) for a formulated battery of geometric and logMAR stimuli was evaluated in participants that had either no eye pathology (healthy participants) or were grouped according to the presence of cataract, pseudophakia, and/or age-related macular degeneration (AMD). PPP was quantified as response frequencies to individual stimuli, and as a novel monocular polarization sensitivity score (Ps) based on perception of the stimulus battery set. Results: Stimulus response frequencies were pattern-dependent and, compared with healthy participants, reduced for cataract and AMD groups but not for subjects with pseudophakia. Compared with healthy eyes (n = 47, median Ps = 17), Ps was significantly reduced by AMD (n = 59, median Ps = 1, P < 0.001) and, to a lesser extent, by cataracts (n = 80, median Ps = 6, P < 0.001). There was no significant difference between Ps for healthy and pseudophakic eyes (n = 47, median Ps = 13, P = 0.323). There was no significant correlation between Ps and logMAR visual acuity. Conclusions: In the absence of significant cataract, or in pseudophakia, a set of polarization-modulated visual stimuli, quantified as the Ps score, distinguishes AMD from healthy maculae. Translational Relevance: Perception of polarization-modulated stimuli, previously shown to be macula-dependent in a laboratory setting, is effective as a test of macular function in health and disease in a clinic setting.

Review of Irish patients meeting ST elevation criteria during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has seen the introduction of important public health measures to minimise the spread of the virus. We aim to identify the impact government restrictions and hospital-based infection control procedures on ST elevation myocardial infarction (STEMI) care during the COVID-19 pandemic. METHODS: Patients meeting ST elevation criteria and undergoing primary percutaneous coronary intervention from 27 March 2020, the day initial national lockdown measures were announced in Ireland, were included in the study. Patients presenting after the lockdown period, from 18 May to 31 June 2020, were also examined. Time from symptom onset to first medical contact (FMC), transfer time and time of wire cross was noted. Additionally, patient characteristics, left ventricular ejection fraction, mortality and biochemical parameters were documented. Outcomes and characteristics were compared against a control group of patients meeting ST elevation criteria during the month of January. RESULTS: A total of 42 patients presented with STEMI during the lockdown period. A significant increase in total ischaemic time (TIT) was noted versus controls (8.81 hours (±16.4) vs 2.99 hours (±1.39), p=0.03), with increases driven largely by delays in seeking FMC (7.13 hours (±16.4) vs 1.98 hours (±1.46), p=0.049). TIT remained significantly elevated during the postlockdown period (6.1 hours (±5.3), p=0.05), however, an improvement in patient delays was seen versus the control group (3.99 hours (±4.5), p=0.06). There was no difference seen in transfer times and door to wire cross time during lockdown, however, a significant increase in transfer times was seen postlockdown versus controls (1.81 hours (±1.0) vs 1.1 hours (±0.87), p=0.004). CONCLUSION: A significant increase in TIT was seen during the lockdown period driven mainly by patient factors highlighting the significance of public health messages on public perception. Additionally, a significant delay in transfer times to our centre was seen postlockdown.