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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)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Enterococcus is ubiquitous in human feces and has been adopted as a useful indicator of human fecal pollution in water. Although regular enterococci monitoring only examines their numbers, identifying human-specific Enterococcus species or genotypes could help discriminate human fecal contamination from other environmental sources. We documented a new approach to characterize enterococci using a high-throughput 16S rRNA gene amplicon sequencing platform from Quanti Trays after following the counting of the most probable numbers of enterococci. We named this method QT-AMP (Quanti-Tray-based amplicon sequencing). We tested surface water samples collected from three rivers in southwest Florida. We detected 11 Enterococcus species from 45 samples in 1.1 million sequence reads. The method detected three rare species and eight cosmopolitan species (Enterococcus faecalis, E. faecium, E. casseliflavus, E. hirae, E. mundtii, E. gallinarum, E. avium, and E. durans) which have been commonly documented in previous studies. The approximate detection level of QT-AMP was four orders of magnitude higher than regular 16S rRNA gene amplicon sequencing. The current Enterolert MPN method only provides quantitative information but now we can look into the relative abundance of Enterococci species composition by accompanying Illumina sequencing. This QT-AMP could be a useful tool to streamline the quantification and identification of enterococci and could be used in various water management projects and human health risk assessment., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (© 2022 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Contact Lens Association of Ophthalmologists.)

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., Competing Interests: The authors have declared that no competing interests exist.

Between October 2020 and January 2021, we conducted three national surveys to track anaesthetic, surgical and critical care activity during the second COVID-19 pandemic wave in the UK. We surveyed all NHS hospitals where surgery is undertaken. Response rates, by round, were 64%, 56% and 51%. Despite important regional variations, the surveys showed increasing systemic pressure on anaesthetic and peri-operative services due to the need to support critical care pandemic demands. During Rounds 1 and 2, approximately one in eight anaesthetic staff were not available for anaesthetic work. Approximately one in five operating theatres were closed and activity fell in those that were open. Some mitigation was achieved by relocation of surgical activity to other locations. Approximately one-quarter of all surgical activity was lost, with paediatric and non-cancer surgery most impacted. During January 2021, the system was largely overwhelmed. Almost one-third of anaesthesia staff were unavailable, 42% of operating theatres were closed, national surgical activity reduced to less than half, including reduced cancer and emergency surgery. Redeployed anaesthesia staff increased the critical care workforce by 125%. Three-quarters of critical care units were so expanded that planned surgery could not be safely resumed. At all times, the greatest resource limitation was staff. Due to lower response rates from the most pressed regions and hospitals, these results may underestimate the true impact. These findings have important implications for understanding what has happened during the COVID-19 pandemic, planning recovery and building a system that will better respond to future waves or new epidemics., (© 2021 Association of Anaesthetists.)

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.

Randomised controlled trials are the gold standard in clinical research, but remain rare due to their expense and a perceived lack of 'real-world' applicability. At the same time, there has been an exponential increase in routinely collected data which presents opportunities for audit, quality improvement, adverse event reporting and more efficient clinical research. Registry-based research benefits from reduced cost, large sample size and real-world applicability, with methodological developments, particularly registry-based randomised controlled trials and causal inference techniques, showing promise. Limitations include data quality and validity, the need for data linkage, the restrictions of fixed data fields, regulatory barriers, and privacy and security concerns. However, the principal factor hampering current efforts is a lack of anaesthesia-specific datasets in the UK and the fact that most surgical registries do not collect any anaesthetic data. This presents an opportunity for anaesthetists, through enhanced engagement and collaboration, to influence and improve the design of these datasets and increase the value and volume of data collected. Better datasets, coupled with a growing appreciation of new analysis methodologies, would allow significant progress towards realising the potential of routinely collected data for patient benefit. At the same time, work should begin on the development of a minimum dataset for anaesthesia to underpin new data sharing networks and, ideally, a national registry of anaesthesia., (© 2020 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

The COVID-19 pandemic continues to cause critical illness and deaths internationally. Up to 31 May 2020, mortality in patients admitted to intensive care units (ICU) with COVID-19 was 41.6%. Since then, changes in therapeutics and management may have improved outcomes. Also, data from countries affected later in the pandemic are now available. We searched MEDLINE, Embase, PubMed and Cochrane databases up to 30 September 2020 for studies reporting ICU mortality among adult patients with COVID-19 and present an updated systematic review and meta-analysis. The primary outcome measure was death in intensive care as a proportion of completed ICU admissions, either through discharge from intensive care or death. We identified 52 observational studies including 43,128 patients, and first reports from the Middle East, South Asia and Australasia, as well as four national or regional registries. Reported mortality was lower in registries compared with other reports. In two regions, mortality differed significantly from all others, being higher in the Middle East and lower in a single registry study from Australasia. Although ICU mortality (95%CI) was lower than reported in June (35.5% (31.3-39.9%) vs. 41.6% (34.0-49.7%)), the absence of patient-level data prevents a definitive evaluation. A lack of standardisation of reporting prevents comparison of cohorts in terms of underlying risk, severity of illness or outcomes. We found that the decrease in ICU mortality from COVID-19 has reduced or plateaued since May 2020 and note the possibility of some geographical variation. More standardisation in reporting would improve the ability to compare outcomes from different reports., (© 2021 Association of Anaesthetists.)

Purpose: Determine the repeatability of and optimum stimulus parameters for testing polarization pattern perception in a real-world clinical population, and assess the ability of polarization perception to distinguish normal from abnormal eyes., Methods: Polarization perception was evaluated in staff and patients attending ophthalmology clinics at Warwick Hospital, UK. A series of visual stimuli were presented in pseudorandom order using a liquid-crystal-display-based polarization pattern generator. Stimuli included geometric patterns, gratings, checkerboards, and optotypes. Participants had one or both eyes diagnosed as normal or abnormal following ophthalmic examination, optical coherence tomography, and measures of visual acuity. Measurement scores were assigned to the eye(s) of each participant depending on the total number of stimuli perceived or identified., Results: Stimuli covered the range of spatial scales resolvable within polarization perception by normal and abnormal eyes. Different stimuli had different saliencies. For each stimulus type, polarization perception in the abnormal group was significantly reduced compared with normal eyes ( P < 0.001). Relative stimulus salience was broadly similar for normal-eye and abnormal-eye viewing groups, being greatest for radially symmetric patterns and least for optotypes. Checkerboard pattern salience had an inverse logarithmic relationship with check fundamental spatial frequency. A devised metric covering the dynamic range of polarization perception was repeatable, and the score derived from the metric was reduced in the abnormal group compared with the normal group ( P < 0.001)., Conclusions: Clinically useful metrics of polarization perception distinguish between normal and abnormal eyes., Translational Relevance: Perception of spatial patterns formed of non-uniform polarization fields has potential as a quantitative clinical diagnostic measurement., Competing Interests: Disclosure: G.P. Misson, None; S.J. Anderson, None; R.A. Armstrong, None; M. Gillett, None; D. Reynolds, None, (Copyright 2020 The Authors.)

The emergence of coronavirus disease 2019 (COVID-19) has led to high demand for intensive care services worldwide. However, the mortality of patients admitted to the intensive care unit (ICU) with COVID-19 is unclear. Here, we perform a systematic review and meta-analysis, in line with PRISMA guidelines, to assess the reported ICU mortality for patients with confirmed COVID-19. We searched MEDLINE, EMBASE, PubMed and Cochrane databases up to 31 May 2020 for studies reporting ICU mortality for adult patients admitted with COVID-19. The primary outcome measure was death in intensive care as a proportion of completed ICU admissions, either through discharge from the ICU or death. The definition thus did not include patients still alive on ICU. Twenty-four observational studies including 10,150 patients were identified from centres across Asia, Europe and North America. In-ICU mortality in reported studies ranged from 0 to 84.6%. Seven studies reported outcome data for all patients. In the remaining studies, the proportion of patients discharged from ICU at the point of reporting varied from 24.5 to 97.2%. In patients with completed ICU admissions with COVID-19 infection, combined ICU mortality (95%CI) was 41.6% (34.0-49.7%), I 2  = 93.2%). Sub-group analysis by continent showed that mortality is broadly consistent across the globe. As the pandemic has progressed, the reported mortality rates have fallen from above 50% to close to 40%. The in-ICU mortality from COVID-19 is higher than usually seen in ICU admissions with other viral pneumonias. Importantly, the mortality from completed episodes of ICU differs considerably from the crude mortality rates in some early reports., (© 2020 Association of Anaesthetists.)

We conducted a survey and semi-structured qualitative interviews to investigate current anaesthetic practice for arteriovenous fistula formation surgery in the UK. Responses were received from 39 out of 59 vascular centres where arteriovenous access surgery is performed, a response rate of 66%. Thirty-five centres reported routine use of brachial plexus blocks, but variation in anaesthetic skill-mix and practice were observed. Interviews were conducted with 19 clinicians from 10 NHS Trusts including anaesthetists, vascular access and renal nurses, surgeons and nephrologists. Thematic analysis identified five key findings: (1) current anaesthetic practice showed that centres could be classified as 'regional anaesthesia dominant' or 'local anaesthesia/mixed'; (2) decision making around mode of anaesthesia highlighted the key role of surgeons as frontline decision makers across both centre types; (3) perceived barriers and facilitators of regional block use included clinicians' beliefs and preferences, resource considerations and patients' treatment preferences; (4) anaesthetists' preference for supraclavicular blocks emerged, alongside acknowledgement of varied practice; (5) there was widespread support for a future randomised controlled trial, although clinician equipoise issues and logistical/resource-related concerns were viewed as potential challenges. The use of regional anaesthesia for arteriovenous fistula formation in the UK is varied and influenced by a multitude of factors. Despite the availability of anaesthetists capable of performing regional blocks, there are other limiting factors that influence the routine use of this technique. The study also highlighted the perceived need for a large multicentre, randomised controlled trial to provide an evidence base to inform current practice., (© 2020 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Stress fractures are common amongst healthy military recruits and athletes. Reduced vitamin D availability, measured by serum 25-hydroxyvitamin D (25OHD) status, has been associated with stress fracture risk during the 32-week Royal Marines (RM) training programme. A gene-environment interaction study was undertaken to explore this relationship to inform specific injury risk mitigation strategies. Fifty-one males who developed a stress fracture during RM training (n = 9 in weeks 1-15; n = 42 in weeks 16-32) and 141 uninjured controls were genotyped for the vitamin D receptor (VDR) FokI polymorphism. Serum 25OHD was measured at the start, middle and end (weeks 1, 15 and 32) of training. Serum 25OHD concentration increased in controls between weeks 1-15 (61.8±29.1 to 72.6±28.8 nmol/L, p = 0.01). Recruits who fractured did not show this rise and had lower week-15 25OHD concentration (p = 0.01). Higher week-15 25OHD concentration was associated with reduced stress fracture risk (adjusted OR 0.55[0.32-0.96] per 1SD increase, p = 0.04): the greater the increase in 25OHD, the greater the protective effect (p = 0.01). The f-allele was over-represented in fracture cases compared with controls (p<0.05). Baseline 25OHD status interacted with VDR genotype: a higher level was associated with reduced fracture risk in f-allele carriers (adjusted OR 0.39[0.17-0.91], p = 0.01). Improved 25OHD status between weeks 1-15 had a greater protective effect in FF genotype individuals (adjusted OR 0.31[0.12-0.81] vs. 1.78[0.90-3.49], p<0.01). Stress fracture risk in RM recruits is impacted by the interaction of VDR genotype with vitamin D status. This further supports the role of low serum vitamin D concentrations in causing stress fractures, and hence prophylactic vitamin D supplementation as an injury risk mitigation strategy., Competing Interests: The authors have declared that no competing interests exist.

Background: Although delivering a chosen mode of anaesthesia for certain emergency surgery procedures is potentially beneficial to patients, it is a complex intervention to evaluate. This qualitative study explored clinician and patient perspectives about mode of anaesthesia for emergency surgery., Methods: Snowball sampling was used to recruit participants from eight National Health Service Trusts that cover the following three emergency surgery settings: ruptured abdominal aortic aneurysms, hip fractures and inguinal hernias. A qualitative researcher conducted interviews with clinicians and patients. Thematic analysis was applied to the interview transcripts., Results: Interviews were conducted with 21 anaesthetists, 21 surgeons, 14 operating theatre staff and 23 patients. There were two main themes. The first, impact of mode of anaesthesia in emergency surgery, had four subthemes assessing clinician and patient ideas about: context and the 'best' mode of anaesthesia; balance in choosing it over others; change and developments in anaesthesia; and the importance of mode of anaesthesia in emergency surgery. The second, tensions in decision-making about mode of anaesthesia, comprised four subthemes: clinical autonomy and guidelines in anaesthesia; conforming to norms in mode of anaesthesia; the relationship between expertise, preference and patient involvement; and team dynamics in emergency surgery. The results highlight several interlinking factors affecting decision-making, including expertise, preference, habit, practicalities, norms and policies., Conclusion: There is variation in practice in choosing the mode of anaesthesia for surgery, alongside debate as to whether anaesthetic autonomy is necessary or results in a lack of willingness to change., (© 2019 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Purpose: Management of traumatic splenic injury may be operative or non-operative (including embolization and conservative management). Traditionally, haemodynamic instability has been an indication for operative intervention. We aimed to report our experience of managing traumatic splenic injury at a regional major trauma centre in the UK over a 4-year period, with a particular focus on the non-operative management (NOM) of haemodynamically unstable patients., Methods: All patients with splenic injuries admitted to North Bristol NHS Trust from April 2012 to March 2016 were included. Patients were classified for analyses by injury severity (low or high grade), haemodynamic instability (defined as a reverse shock index < 1) and management category (operative or non-operative)., Results: 106 patients were included. Overall 85.8% of patients received NOM: 79.2% conservative and 6.6% interventional radiology. Two patients (2.4%) managed conservatively required further intervention. Haemodynamically stable and unstable patients were equally likely to receive NOM (89.7 and 81.3% respectively, p = 1). All unstable patients with low-grade injuries were managed conservatively and only one (2.7%) required further intervention. Two unstable patients with high-grade injuries (28.6%) underwent NOM successfully., Conclusions: These data support the safe application of non-operative management to haemodynamically unstable patients with traumatic splenic injury, particularly in those with low-grade injuries. Additional prospective work is required to define the subgroup of patients for whom this is appropriate and to determine the long-term outcomes of NOM.

Purpose: To survey the use of Pearson's correlation coefficient (r) and related statistical methods in the ophthalmic literature, to consider the limitations of r, and to suggest suitable alternative methods of analysis., Recent Findings: Searching Ophthalmic and Physiological Optics (OPO), Optometry and Vision Science (OVS), and Clinical and Experimental Optometry (CXO) online archives using correlation and Pearson's r as search terms resulted in 4057 and 281 hits respectively. Coefficient of determination, r square, or r squared received fewer hits (65, 8, and 22 hits respectively). The assumption that r follows a bivariate normal distribution was rarely encountered (3 hits) although several studies applied Spearman's rank correlation (70 hits). The intra-class correlation coefficient (ICC) was widely used (178 hits), but fewer hits were recorded for partial correlation (43 hits) and multiple correlation (13) hits. There was little evidence that the problem of sample size was addressed in correlation studies., Summary: Investigators should be alert to whether: (1) the relationship between two variables could be non-linear, (2) the data are bivariate normal, (3) r accounts for a significant proportion of the variance in Y, (4) outliers are present, the data are clustered, or have a restricted range, (5) the sample size is appropriate, and (6) a significant correlation indicates causality. In addition, the number of significant digits used to express r and the problems of multiple testing should be addressed. The problems and limitations of r suggest a more cautious approach regarding its use and the application of alternative methods where appropriate., (© 2019 The Authors Ophthalmic & Physiological Optics © 2019 The College of Optometrists.)

Rationale: Oxygen isotope ratios (δ 18 O values) of fish otoliths (ear bones) are valuable geochemical tracers of water conditions and thermal life history. Delta Smelt (Hypomesus transpacificus) are osmerid forage fish endemic to the San Francisco Estuary, California, USA, that are on the verge of extinction. These fish exhibit a complex life history that allows them to survive in a dynamic estuarine environment; however, a rapidly warming climate threatens this thermally sensitive species. Here we quantify the accuracy and precision of using δ 18 O values in otoliths to reconstruct the thermal life histories of Delta Smelt., Methods: Delta Smelt were reared for 360 days using three different water sources with different ambient δ 18 O water values (-8.75‰, -5.28‰, and -4.06‰) and different water temperatures (16.4°C, 16.7°C, 18.7°C, and 20.5°C). Samples were collected after 170 days (n = 28) and 360 days (n = 14) post-hatch. In situ δ 18 O values were measured from the core of the otolith to the dorsal edge using secondary ion mass spectrometry (SIMS) to reconstruct temporally resolved thermal life histories., Results: The δ 18 O otolith values for Delta Smelt varied as a linear inverse function of water temperature: 1000 ln α = 18.39 (±0.43, 1SE)(10 3 TK -1 ) - 34.56 (±1.49, 1SE) and δ 18 O otolith(VPDB)  - δ 18 O water (VPDB)  = 31.34(±0.09, 1SE) - 0.19(±0.01, 1SE) × T ° C. When the ambient δ 18 O water value is known, this species-specific temperature-dependent oxygen isotope fractionation model facilitated the accurate (0.25°C) and precise (±0.37°C, 2σ) reconstruction of the water temperature experienced by the fish. In contrast, the use of existing general fractionation equations resulted in inaccurate temperature reconstructions., Conclusions: The species-specific δ 18 O otolith fractionation equation allowed for accurate and precise reconstructions of water temperatures experienced by Delta Smelt. Characterization of ambient δ 18 O water values remains a critical next step for reconstructing thermal life histories of wild Delta Smelt. This tool will provide new insights into habitat utilization, potential thermal refugia, and resilience to future warming for this critically endangered fish., (© 2019 John Wiley & Sons, Ltd.)

The incidence of cardiac arrest in the intensive care unit (ICU-CA) has not been widely reported. We undertook a systematic review and meta-analysis of studies reporting the incidence of cardiac arrest in adult, general intensive care units. The review was prospectively registered with PROSPERO (CRD42017079717). The search identified 7550 records, which included 20 relevant studies for qualitative analysis and 16 of these were included for quantitative analyses. The reported incidence of ICU-CA was 22.7 per 1000 admissions (95% CI: 17.4-29.6) with survival to hospital discharge of 17% (95% CI: 9.5-28.5%). We estimate that at least 5446 patients in the UK have a cardiac arrest after ICU admission. There are limited data and significant variation in the incidence of ICU-CA and efforts to synthesise these are limited by inconsistent reporting. Further prospective studies with standardised process and incidence measures are required to define this important patient group.

Objectives: An observational study to compare the laminar distributions in frontal and temporal cortex of the tau-immunoreactive pathologies in chronic traumatic encephalopathy (CTE) and Alzheimer's disease neuropathologic change (ADNC)., Patients: Post-mortem material of (1) four cases of CTE without ADNC, (2) seven cases of CTE with ADNC (CTE/ADNC), and (3) seven cases of ADNC alone., Results: In CTE and CTE/ADNC, neurofibrillary tangles (NFT), neuropil threads (NT), and dot-like grains (DLG) were distributed either in upper cortex or across all layers. Low densities of astrocytic tangles (AT) and abnormally enlarged neurons (EN) were not localized to any specific layer. Surviving neurons exhibited peaks of density in both upper and lower cortex, and vacuole density was greatest in superficial layers. In ADNC, neuritic plaques (NP) were more frequent, AT rare, NFT and NT were more widely distributed, NT affected lower layers more frequently, and surviving neurons were less frequently bimodal than in CTE and CTE/ADNC., Conclusion: Tau pathology in CTE and CTE/ADNC consistently affected the upper cortex but was more widely distributed in ADNC. The presence of CTE may encourage the development of ADNC pathology later in the course of the disease.

Objective: Endovascular aneurysm repair (EVAR) is used increasingly in the management of patients with abdominal aortic aneurysms (AAAs), including in the emergency setting for ruptured AAA. The lower mortality among patients undergoing emergency EVAR under local anesthesia (LA) observed in the Immediate Management of Patients with Rupture: Open Versus Endovascular Repair trial has sparked renewed interest in the anesthesia choice for EVAR. This systematic review evaluates the effect of mode of anesthesia on outcomes after EVAR., Design: The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The primary outcome was in-hospital/30-day mortality, and both emergency and elective EVAR were included. The relative risk of death was estimated for each individual study without adjustment for potential confounding factors., Setting: Hospitals., Participants: A total of 39,744 patients from 22 nonrandomized studies were included in the analysis., Interventions: None., Measurements and Main Results: Sixteen studies in 23,202 patients compared LA to general anesthesia (GA) and reported in-hospital/30-day mortality. The unadjusted risk of death after emergency EVAR with LA was lower than with GA. Trends in elective surgery were less clear., Conclusion: There is some evidence across both emergency and elective settings to suggest that mode of anesthesia may be associated with improved outcomes. In particular, LA appears to have a positive effect on outcome after emergency EVAR. Because of the lack of randomized trial data, a significant risk of confounding remains. The optimal mode of anesthesia for EVAR should be investigated further and the reasons why particular anesthesia techniques are chosen for particular patients identified., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) and its associated concussion are major causes of disability and death. All ages can be affected but children, young adults and the elderly are particularly susceptible. A decline in mortality has resulted in many more individuals living with a disability caused by TBI including those affecting vision. This review describes: (1) the major clinical and pathological features of TBI; (2) the visual signs and symptoms associated with the disorder; and (3) discusses the assessment of quality of life and visual rehabilitation of the patient. Defects in primary vision such as visual acuity and visual fields, eye movement including vergence, saccadic and smooth pursuit movements, and in more complex aspects of vision involving visual perception, motion vision ('akinopsia'), and visuo-spatial function have all been reported in TBI. Eye movement dysfunction may be an early sign of TBI. Hence, TBI can result in a variety of visual problems, many patients exhibiting multiple visual defects in combination with a decline in overall health. Patients with chronic dysfunction following TBI may require occupational, vestibular, cognitive and other forms of physical therapy. Such patients may also benefit from visual rehabilitation, including reading-related oculomotor training and the prescribing of spectacles with a variety of tints and prism combinations., (© 2018 Optometry Australia.)

Aims: To characterize the topography of white matter pathology in neuronal intermediate filament inclusion disease (NIFID), a rare subtype of frontotemporal lobar degeneration (FTLD) with "fused in sarcoma" (FUS)-immunoreactive inclusions., Material and Methods: Fiber tracts from frontal and temporal lobes of 10 cases of NIFID., Method: Spatial patterns of the vacuolation, glial cell nuclei, and glial inclusions (GI) were studied across cortical fiber tracts from each case., Results: Vacuoles and glial cells in NIFID were distributed either in regularly-distributed clusters or in large diffuse clusters contrasting with typical control cases in which smaller clusters of glial cells were surrounded by more compact clusters of vacuoles. Axonal varicosities and GI were also observed in the precentral gyrus (PCG) of 4 NIFID cases. Depending on region, the densities of glial cells and vacuoles were either positively or negatively spatially correlated, but there were no spatial correlations between the densities of the GI and either the vacuoles or glial cells. Spatial patterns in white matter were similar to those reported in adjacent gray matter., Conclusion: 1) Pathological changes across the white matter in NIFID are topographically distributed, 2) there is a correlation between the development of vacuolation and gliosis, and 3) white matter and gray matter pathologies are closely related.
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Purpose: A common experimental design in ophthalmic research is the repeated-measures design in which at least one variable is a within-subject factor. This design is vulnerable to lack of 'sphericity' which assumes that the variances of the differences among all possible pairs of within-subject means are equal. Traditionally, this design has been analysed using a repeated-measures analysis of variance (RM-anova) but increasingly more complex methods such as multivariate anova (manova) and mixed model analysis (MMA) are being used. This article surveys current practice in the analysis of designs incorporating different factors in research articles published in three optometric journals, namely Ophthalmic and Physiological Optics (OPO), Optometry and Vision Science (OVS), and Clinical and Experimental Optometry (CXO), and provides advice to authors regarding the analysis of repeated-measures designs., Recent Findings: Of the total sample of articles, 66% used a repeated-measures design. Of those articles using a repeated-measures design, 59% and 8% analysed the data using RM-anova or manova respectively and 33% used MMA. The use of MMA relative to RM-anova has increased significantly since 2009/10. A further search using terms to select those papers testing and correcting for sphericity ('Mauchly's test', 'Greenhouse-Geisser', 'Huynh and Feld') identified 66 articles, 62% of which were published from 2012 to the present., Summary: If the design is balanced without missing data then manova should be used rather than RM-anova as it gives better protection against lack of sphericity. If the design is unbalanced or with missing data then MMA is the method of choice. However, MMA is a more complex analysis and can be difficult to set up and run, and care should be taken first, to define appropriate models to be tested and second, to ensure that sample sizes are adequate., (© 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.)

To investigate cortical laminar degeneration in Parkinson's disease (PD) with dementia (PDD). Changes in density of α-synuclein-immunoreactive Lewy bodies (LB), Lewy neurites (LN), and Lewy grains (LG) together with surviving neurons, abnormally enlarged neurons (EN), vacuoles, and glial cell nuclei were measured across cortical laminae of frontal and temporal cortex in fifteen cases of PDD using quantitative methods and polynomial curve-fitting. Most frequently, LB and LN were distributed across all laminae, while LG were distributed in upper cortical laminae. Low densities of EN were present in most cases distributed across all cortical laminae. Densities of vacuoles and glia were greatest in upper and lower cortical laminae, respectively. In most gyri, there were no spatial correlations between the densities of LB, LN, and LG. Cortical degeneration of frontal and temporal lobes in PDD affects all cortical laminae. Laminar distributions may result from the spread of α-synuclein pathology from subcortical regions and subsequent spread via the cortico-cortical pathways. This spread may be a major factor in the development of dementia in PD.

Aims: To characterize white matter pathology in frontotemporal lobar degeneration (FTLD) with TDP-43 proteinopathy (FTLD-TDP) and its relationship to gray matter pathology., Material: Fiber tracts from frontal and temporal lobes of 10 sporadic cases of FTLD and 8 controls., Method: Density and spatial patterns of vacuolation, glial cell nuclei, and glial inclusions (GI) were studied in 4 fiber tracts from each case., Results: Densities of vacuoles but not glial cells were greater in FTLD-TDP than controls. No GI were observed in controls, while in FTLD-TDP, greatest densities of GI were observed in the cortex of early-onset cases. Vacuoles, glial cell nuclei, and GI were distributed in clusters which were regularly distributed across the tract. Densities of vacuoles in white matter were positively correlated with those in adjacent gray matter, and correlations were also present between GI in white matter and TDP-43-immunoreactive pathology in gray matter., Conclusions: (1) Degeneration of white matter in sporadic FTLD-TDP was characterized by increased vacuolation and GI, (2) pathological changes were topographically distributed, which suggests propagation of pathological TDP-43 in specific groups of fibers, and (3) both white matter pathology and gray matter pathology need to be considered to quantify the pathological "load" in FTLD-TDP.
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Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder which may result from repetitive brain injury. A variety of tau-immunoreactive pathologies are present, including neurofibrillary tangles (NFT), neuropil threads (NT), dot-like grains (DLG), astrocytic tangles (AT), and occasional neuritic plaques (NP). In tauopathies, cellular inclusions in the cortex are clustered within specific laminae, the clusters being regularly distributed parallel to the pia mater. To determine whether a similar spatial pattern is present in CTE, clustering of the tau-immunoreactive pathology was studied in the cortex, hippocampus, and dentate gyrus in 11 cases of CTE and 7 cases of Alzheimer's disease neuropathologic change (ADNC) without CTE. In CTE: (1) all aspects of tau-immunoreactive pathology were clustered and the clusters were frequently regularly distributed parallel to the tissue boundary, (2) clustering was similar in two CTE cases with minimal co-pathology compared with cases with associated ADNC or TDP-43 proteinopathy, (3) in a proportion of cortical gyri, estimated cluster size was similar to that of cell columns of the cortico-cortical pathways, and (4) clusters of the tau-immunoreactive pathology were infrequently spatially correlated with blood vessels. The NFT and NP in ADNC without CTE were less frequently randomly or uniformly distributed and more frequently in defined clusters than in CTE. Hence, the spatial pattern of the tau-immunoreactive pathology observed in CTE is typical of the tauopathies but with some distinct differences compared to ADNC alone. The spread of pathogenic tau along anatomical pathways could be a factor in the pathogenesis of the disease., Competing Interests: Other than the stated grants, the authors report no conflicts of interest.

Aims: To quantify tau pathology of chronic traumatic encephalopathy (CTE) and investigate influence of dot-like lesions (DL), brain region, comorbidity and sporting career length., Methods: Densities of neurofibrillary tangles (NFT), astrocytic tangles (AT), DL, oligodendroglial inclusions (GI), neuropil threads (NT), vacuoles, neurons and enlarged neurons (EN) were measured in tau-immunoreactive sections of upper cortical laminae of frontal and temporal lobes, hippocampus (HC), amygdala and substantia nigra (SN) in 11 cases of CTE., Results: DL were a consistent finding in CTE. Densities of NFT, NT and DL were greatest in sectors CA1 and CA2 of the HC. Densities of AT were lower than NFT, small numbers of GI were recorded in temporal lobe and low densities of vacuoles and EN were consistently present. β-Amyloid-containing neuritic plaques (NP) also occurred at low density. Densities of NFT, NT, DL and AT were greater in sulci than gyri, while vacuole density was greater in gyri. Principal components analysis (PCA) suggested that sporting career length and densities of NFT in entorhinal cortex, NT in CA2 and SN and vacuolation in the DG were significant sources of variation among cases., Conclusion: DL are frequent in CTE suggesting affinity with argyrophilic grain disease (AGD) and Parkinson's disease dementia (PD-Dem). Densities of AT in all regions and NT/DL in sectors CA2/4 were consistent features of CTE. The 11 cases are neuropathologically heterogeneous which may result from genetic diversity, and variation in anatomical pathways subjected to trauma., (© 2016 British Neuropathological Society.)

This chapter describes the visual problems likely to be encountered in Parkinson's disease (PD) and whether such signs are useful in differentiating the parkinsonian syndromes. Visual dysfunction in PD may involve visual acuity, contrast sensitivity, color discrimination, pupil reactivity, saccadic and pursuit eye movements, motion perception, visual fields, and visual processing speeds. In addition, disturbance of visuospatial orientation, facial recognition problems, rapid eye movement (REM) sleep behavior disorder, and chronic visual hallucinations may be present. Problems affecting pupil reactivity, stereopsis, pursuit eye movement, and visuomotor adaptation, when accompanied by REM sleep behavior disorder, could be early features of PD. Dementia associated with PD is associated with enhanced eye movement problems, visuospatial deficits, and visual hallucinations. Visual dysfunction may be a useful diagnostic feature in differentiating PD from other parkinsonian symptoms, visual hallucinations, visuospatial dysfunction, and variation in saccadic eye movement problems being particularly useful discriminating features., (© 2017 Elsevier Inc. All rights reserved.)

Purpose: To investigate neuropathological changes in the superior colliculus in chronic traumatic encephalopathy., Methods: The densities of the tau-immunoreactive neurofibrillary tangles, neuropil threads, dot-like grains, astrocytic tangles, and neuritic plaques, together with abnormally enlarged neurons, typical neurons, vacuolation, and frequency of contacts with blood vessels, were studied across the superior colliculus from pia mater to the periaqueductal gray in eight chronic traumatic encephalopathy and six control cases., Results: Tau-immunoreactive pathology was absent in the superior colliculus of controls but present in varying degrees in all chronic traumatic encephalopathy cases, significant densities of tau-immunoreactive neurofibrillary tangles, NT, or dot-like grains being present in three cases. No significant differences in overall density of the tau-immunoreactive neurofibrillary tangles, neuropil threads, dot-like grains, enlarged neurons, vacuoles, or contacts with blood vessels were observed in control and chronic traumatic encephalopathy cases, but chronic traumatic encephalopathy cases had significantly lower mean densities of neurons. The distribution of surviving neurons across the superior colliculus suggested greater neuronal loss in intermediate and lower laminae in chronic traumatic encephalopathy. Changes in density of the tau-immunoreactive pathology across the laminae were variable, but in six chronic traumatic encephalopathy cases, densities of tau-immunoreactive neurofibrillary tangles, neuropil threads, or dot-like grains were significantly greater in intermediate and lower laminae. Pathological changes were not correlated with the distribution of blood vessels., Conclusions: The data suggest significant pathology affecting the superior colliculus in a proportion of chronic traumatic encephalopathy cases with a laminar distribution which could compromise motor function rather than sensory analysis.

Corticobasal degeneration is a rare, progressive neurodegenerative disease and a member of the 'parkinsonian' group of disorders, which also includes Parkinson's disease, progressive supranuclear palsy, dementia with Lewy bodies and multiple system atrophy. The most common initial symptom is limb clumsiness, usually affecting one side of the body, with or without accompanying rigidity or tremor. Subsequently, the disease affects gait and there is a slow progression to influence ipsilateral arms and legs. Apraxia and dementia are the most common cortical signs. Corticobasal degeneration can be difficult to distinguish from other parkinsonian syndromes but if ocular signs and symptoms are present, they may aid clinical diagnosis. Typical ocular features include increased latency of saccadic eye movements ipsilateral to the side exhibiting apraxia, impaired smooth pursuit movements and visuo-spatial dysfunction, especially involving spatial rather than object-based tasks. Less typical features include reduction in saccadic velocity, vertical gaze palsy, visual hallucinations, sleep disturbance and an impaired electroretinogram. Aspects of primary vision such as visual acuity and colour vision are usually unaffected. Management of the condition to deal with problems of walking, movement, daily tasks and speech problems is an important aspect of the disease., (© 2016 Optometry Australia.)

Background: The aim was to derive equations for the relationship between unaided vision and age, pupil diameter, iris colour and sphero-cylindrical refractive error., Methods: Data were collected from 663 healthy right eyes of white subjects aged 20 to 70 years. Subjective sphero-cylindrical refractive errors ranged from -6.8 to +9.4 D (mean spherical equivalent), -1.5 to +1.9 D (orthogonal component, J0 ) and -0.8 to 1.0 D (oblique component, J45 ). Cylinder axis orientation was orthogonal in 46 per cent of the eyes and oblique in 18 per cent. Unaided vision (-0.3 to +1.3 logMAR), pupil diameter (2.3 to 7.5 mm) and iris colour (67 per cent light/blue irides) was recorded. The sample included mostly females (60 per cent) and many contact lens wearers (42 per cent) and so the influences of these parameters were also investigated., Results: Decision tree analysis showed that sex, iris colour, contact lens wear and cylinder axis orientation did not influence the relationship between unaided vision and refractive error. New equations for the dependence of the minimum angle of resolution on age and pupil diameter arose from step backwards multiple linear regressions carried out separately on the myopes (2.91.scalar vector +0.51.pupil diameter -3.14 ) and hyperopes (1.55.scalar vector + 0.06.age - 3.45 )., Conclusion: The new equations may be useful in simulators designed for teaching purposes as they accounted for 81 per cent (for myopes) and 53 per cent (for hyperopes) of the variance in measured data. In comparison, previously published equations accounted for not more than 76 per cent (for myopes) and 24 per cent (for hyperopes) of the variance depending on whether they included pupil size. The new equations are, as far as is known to the authors, the first to include age. The age-related decline in accommodation is reflected in the equation for hyperopes., (© 2016 Optometry Australia.)

Traditional methods of describing and classifying neurodegenerative disease are based on the clinico-pathological concept supported by molecular pathological studies and defined by 'consensus criteria'. Disease heterogeneity, overlap between disorders, and the presence of multiple co-pathologies, however, have questioned the validity and status of many traditional disorders. If cases of neurodegenerative disease are not easily classifiable into distinct entities, but more continuously distributed, then a new descriptive framework may be required. This review proposes that there are four key neuropathological features of neurodegenerative disease (the 'primary determinants') that could be used to provide such a framework, viz., the anatomical pathways affected by the disease ('anatomy'), the cell populations affected ('cells'), the molecular pathology of 'signature' pathological lesions ('molecules'), and the morphological types of neurodegeneration ('morphology'). This review first discusses the limitations of existing classificatory systems and second provides evidence that the four primary determinants could be used as axes to define all cases of neurodegenerative disease. To illustrate the methodology, the primary determinants were applied to the study of a group of closely related tauopathy cases and to heterogeneity within frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP).

Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64). Familial and sporadic cases exhibited similar survival, including progranulin (GRN) gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight. Survival was significantly reduced in cases with associated motor neuron disease (FTLD-MND) but increased with Alzheimer's disease (AD) or hippocampal sclerosis (HS) co-morbidity. Cox regression analysis suggested that reduced survival was associated with increased densities of neuronal cytoplasmic inclusions (NCI) while increased survival was associated with greater densities of enlarged neurons (EN) in the frontal and temporal lobes. The data suggest that: (1) survival in FTLD-TDP is more prolonged than typical in pre-senile dementia but shorter than some clinical subtypes such as the semantic variant of primary progressive aphasia (svPPA), (2) MND co-morbidity predicts poor survival, and (3) NCI may develop early and EN later in the disease. The data have implications for both neuropathological characterization and subtyping of FTLD-TDP.

Reef corals typically contain a number of pigments, mostly due to their symbiotic relationship with photosynthetic dinoflagellates. These pigments usually vary in presence and concentration and influence the spectral characteristics of corals. We studied the variations in pigment composition among seven Caribbean shallow-water Scleractinian corals by means of High Performance Liquid Chromatography (HPLC) analysis to further resolve the discrimination of corals. We found a total of 27 different pigments among the coral species, including some alteration products of the main pigments. Additionally, pigments typically found in endolithic algae were also identified. A Principal Components Analysis and a Hierarchical Cluster Analysis showed the separation of coral species based on pigment composition. All the corals were collected under the same physical environmental conditions. This suggests that pigment in the coral's symbionts might be more genetically-determined than influenced by prevailing physical conditions of the reef. We further investigated the use of remote sensing reflectance (Rrs) as a tool for estimating the total pigment concentration of reef corals. Depending on the coral species, the Rrs and the total symbiont pigment concentration per coral tissue area correlation showed 79.5-98.5% confidence levels demonstrating its use as a non-invasive robust technique to estimate pigment concentration in studies of coral reef biodiversity and health.

The hippocampus (HC) and adjacent gyri are implicated in dementia in several neurodegenerative disorders. To compare HC pathology among disorders, densities of 'signature' pathological lesions were measured at a standard location in eight brain regions of 12 disorders. Principal components analysis of the data suggested that the disorders could be divided into three groups: (1) Alzheimer's disease (AD), Down's syndrome (DS), sporadic Creutzfeldt-Jakob disease, and variant Creutzfeldt-Jakob disease in which either β-amyloid (Aβ) or prion protein deposits were distributed in all sectors of the HC and adjacent gyri, with high densities being recorded in the parahippocampal gyrus and subiculum; (2) Pick's disease, sporadic frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions, and neuronal intermediate filament inclusion disease in which relatively high densities of neuronal cytoplasmic inclusions were present in the dentate gyrus (DG) granule cells; and (3) Parkinson's disease dementia, dementia with Lewy bodies, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy in which densities of signature lesions were relatively low. Variation in density of signature lesions in DG granule cells and CA1 were the most important sources of neuropathological variation among disorders. Hence, HC and adjacent gyri are differentially affected in dementia reflecting either variation in vulnerability of hippocampal neurons to specific molecular pathologies or in the spread of pathological proteins to the HC. Information regarding the distribution of pathology could ultimately help to explain variations in different cognitive domains, such as memory, observed in various disorders.

Kimberlites and orangeites (previously named Group-II kimberlites) are small-volume igneous rocks occurring in diatremes, sills and dykes. They are the main hosts for diamonds and are of scientific importance because they contain fragments of entrained mantle and crustal rocks, thus providing key information about the subcontinental lithosphere. Orangeites are ultrapotassic, H2O and CO2-rich rocks hosting minerals such as phlogopite, olivine, calcite and apatite. The major, trace element and isotopic compositions of orangeites resemble those of intensely metasomatized mantle of the type represented by MARID (mica-amphibole-rutile-ilmenite-diopside) xenoliths. Here we report new data for two MARID xenoliths from the Bultfontein kimberlite (Kimberley, South Africa) and we show that MARID-veined mantle has mineralogical (carbonate-apatite) and geochemical (Sr-Nd-Hf-O isotopes) characteristics compatible with orangeite melt generation from a MARID-rich source. This interpretation is supported by U-Pb zircon ages in MARID xenoliths from the Kimberley kimberlites, which confirm MARID rock formation before orangeite magmatism in the area.

Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make life style choices that may reduce the risk of disease. This review discusses the role of genetics, sunlight, diet, cardiovascular factors, smoking, and alcohol as possible risk factors for AMD. Genetics plays a more significant role in AMD than previously thought, especially in younger patients, histocompatibility locus antigen (HLA) and complement system genes being the most significant. Whether the risk of AMD is increased by exposure to sunlight, cardiovascular risk factors, and diet is more controversial. Smoking is the risk factor most consistently associated with AMD. Current smokers are exposed to a two to three times higher risk of AMD than non-smokers and the risk increases with intensity of smoking. Moderate alcohol consumption is unlikely to increase the risk of AMD. Optometrists as front-line informers and educators of ocular health play a significant role in increasing public awareness of the risks of AMD. Cessation of smoking, the use of eye protection in high light conditions, dietary changes, and regular use of dietary supplements should all be considered to reduce the lifetime risk of AMD.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder associated with parkinsonism, ataxia, and autonomic dysfunction. Its pathology is primarily subcortical comprising vacuolation, neuronal loss, gliosis, and α-synucleinimmunoreactive glial cytoplasmic inclusions (GCI). To quantify cerebellar pathology in MSA, the density and spatial pattern of the pathological changes were studied in α-synuclein-immunolabelled sections of the cerebellar hemisphere in 10 MSA and 10 control cases. In MSA, densities of Purkinje cells (PC) were decreased and vacuoles in the granule cell layer (GL) increased compared with controls. In six MSA cases, GCI were present in cerebellar white matter. In the molecular layer (ML) and GL of MSA, vacuoles were clustered, the clusters exhibiting a regular distribution parallel to the edge of the folia. Purkinje cells were randomly or regularly distributed with large gaps between surviving cells. Densities of glial cells and surviving neurons in the ML and surviving cells and vacuoles in the GL were negatively correlated consistent with gliosis and vacuolation in response to neuronal loss. Principal components analysis (PCA) suggested vacuole densities in the ML and vacuole density and cell losses in the GL were the main source of neuropathological variation among cases. The data suggest that: (1) cell losses and vacuolation of the GCL and loss of PC were the most significant pathological changes in the cases studied, (2) pathological changes were topographically distributed, and (3) cerebellar pathology could influence cerebral function in MSA via the cerebello-dentato-thalamic tract.

To determine whether genetic factors influence frontal lobe degeneration in Alzheimer's disease (AD), the laminar distributions of diffuse, primitive, and classic β-amyloid (Aβ) peptide deposits were compared in early-onset familial AD (EO-FAD) linked to mutations of the amyloid precursor protein (APP) or presenilin 1 (PSEN1) gene, late-onset familial AD (LO-FAD), and sporadic AD (SAD). The influence of apolipoprotein E (Apo E) genotype on laminar distribution was also studied. In the majority of FAD and SAD cases, maximum density of the diffuse and primitive Aβdeposits occurred in the upper cortical layers, whereas the distribution of the classic Aβ deposits was more variable, either occurring in the lower layers, or a double-peaked (bimodal) distribution was present, density peaks occurring in upper and lower layers. The cortical layer at which maximum density of Aβ deposits occurred and maximum density were similar in EO-FAD, LO-FAD and SAD. In addition, there were no significant differences in distributions in cases expressing Apo E ε4 alleles compared with cases expressing the ε2 or ε3 alleles. These results suggest that gene expression had relatively little effect on the laminar distribution of Aβ deposits in the frontal lobe of the AD cases studied. Hence, the pattern of frontal lobe degeneration in AD is similar regardless of whether it is associated with APP and PSEN1, mutation, allelic variation in Apo E, or with SAD.

This review describes the oculo-visual problems likely to be encountered in Parkinson's disease (PD) with special reference to three questions: (1) are there visual symptoms characteristic of the prodromal phase of PD, (2) is PD dementia associated with specific visual changes, and (3) can visual symptoms help in the differential diagnosis of the parkinsonian syndromes, viz. PD, progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and corticobasal degeneration (CBD)? Oculo-visual dysfunction in PD can involve visual acuity, dynamic contrast sensitivity, colour discrimination, pupil reactivity, eye movement, motion perception, and visual processing speeds. In addition, disturbance of visuo-spatial orientation, facial recognition problems, and chronic visual hallucinations may be present. Prodromal features of PD may include autonomic system dysfunction potentially affecting pupil reactivity, abnormal colour vision, abnormal stereopsis associated with postural instability, defects in smooth pursuit eye movements, and deficits in visuo-motor adaptation, especially when accompanied by idiopathic rapid eye movement (REM) sleep behaviour disorder. PD dementia is associated with the exacerbation of many oculo-visual problems but those involving eye movements, visuo-spatial function, and visual hallucinations are most characteristic. Useful diagnostic features in differentiating the parkinsonian symptoms are the presence of visual hallucinations, visuo-spatial problems, and variation in saccadic eye movement dysfunction.

Familial frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP) is most commonly caused by progranulin (GRN) gene mutation. To characterize cortical degeneration in these cases, changes in density of the pathology across the cortical laminae of the frontal and temporal lobe were studied in seven cases of FTLD-TDP with GRN mutation using quantitative analysis and polynomial curve fitting. In 50% of gyri studied, neuronal cytoplasmic inclusions (NCI) exhibited a peak of density in the upper cortical laminae. Most frequently, neuronal intranuclear inclusions (NII) and dystrophic neurites (DN) exhibited a density peak in lower and upper laminae, respectively, glial inclusions (GI) being distributed in low densities across all laminae. Abnormally enlarged neurons (EN) were distributed either in the lower laminae or were more uniformly distributed across the cortex. The distribution of all neurons present varied between cases and regions, but most commonly exhibited a bimodal distribution, density peaks occurring in upper and lower laminae. Vacuolation primarily affected the superficial laminae and density of glial cell nuclei increased with distance across the cortex from pia mater to white matter. The densities of the NCI, GI, NII, and DN were not spatially correlated. The laminar distribution of the pathology in GRN mutation cases was similar to previously reported sporadic cases of FTLD-TDP. Hence, pathological changes initiated by GRN mutation, and by other causes in sporadic cases, appear to follow a parallel course resulting in very similar patterns of cortical degeneration in FTLD-TDP.

Multiple system atrophy (MSA) is a rare movement disorder and a member of the 'parkinsonian syndromes', which also include Parkinson's disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB) and corticobasal degeneration (CBD). Multiple system atrophy is a complex syndrome, in which patients exhibit a variety of signs and symptoms, including parkinsonism, ataxia and autonomic dysfunction. It can be difficult to separate MSA from the other parkinsonian syndromes but if ocular signs and symptoms are present, they may aid differential diagnosis. Typical ocular features of MSA include blepharospasm, excessive square-wave jerks, mild to moderate hypometria of saccades, impaired vestibular-ocular reflex (VOR), nystagmus and impaired event-related evoked potentials. Less typical features include slowing of saccadic eye movements, the presence of vertical gaze palsy, visual hallucinations and an impaired electroretinogram (ERG). Aspects of primary vision such as visual acuity, colour vision or visual fields are usually unaffected. Management of the disease to deal with problems of walking, movement, daily tasks and speech problems is important in MSA. Optometrists can work in collaboration with the patient and health-care providers to identify and manage the patient's visual deficits. A more specific role for the optometrist is to correct vision to prevent falls and to monitor the anterior eye to prevent dry eye and control blepharospasm., (© 2014 The Author. Clinical and Experimental Optometry © 2014 Optometrists Association Australia.)

Purpose: The Bonferroni correction adjusts probability (p) values because of the increased risk of a type I error when making multiple statistical tests. The routine use of this test has been criticised as deleterious to sound statistical judgment, testing the wrong hypothesis, and reducing the chance of a type I error but at the expense of a type II error; yet it remains popular in ophthalmic research. The purpose of this article was to survey the use of the Bonferroni correction in research articles published in three optometric journals, viz. Ophthalmic & Physiological Optics, Optometry & Vision Science, and Clinical & Experimental Optometry, and to provide advice to authors contemplating multiple testing., Recent Findings: Some authors ignored the problem of multiple testing while others used the method uncritically with no rationale or discussion. A variety of methods of correcting p values were employed, the Bonferroni method being the single most popular. Bonferroni was used in a variety of circumstances, most commonly to correct the experiment-wise error rate when using multiple 't' tests or as a post-hoc procedure to correct the family-wise error rate following analysis of variance (anova). Some studies quoted adjusted p values incorrectly or gave an erroneous rationale., Summary: Whether or not to use the Bonferroni correction depends on the circumstances of the study. It should not be used routinely and should be considered if: (1) a single test of the 'universal null hypothesis' (Ho ) that all tests are not significant is required, (2) it is imperative to avoid a type I error, and (3) a large number of tests are carried out without preplanned hypotheses., (© 2014 The Authors Ophthalmic & Physiological Optics © 2014 The College of Optometrists.)