Physiological condition infers habitat choice in juvenile sockeye salmon.

The amount of time that juvenile salmon remain in an estuary varies among and within populations, with some individuals passing through their estuary in hours while others remain in the estuary for several months. Underlying differences in individual physiological condition, such as body size, stored energy and osmoregulatory function, could drive individual variation in the selection of estuary habitat. Here we investigated the role of variation in physiological condition on the selection of estuarine and ocean habitat by sockeye salmon (Oncorhynchus nerka) smolts intercepted at the initiation of their 650-km downstream migration from Chilko Lake, Fraser River, British Columbia (BC). Behavioural salinity preference experiments were conducted on unfed smolts held in fresh water at three time intervals during their downstream migration period, representing the stage of migration at lake-exit, and the expected timing for estuary-entry and ocean-entry (0, 1 and 3 weeks after lake-exit, respectively). In general, salinity preference behaviour varied across the three time periods consistent with expected transition from river to estuary to ocean. Further, individual physiological condition did influence habitat choice. Smolt condition factor (K) and energy density were positively correlated with salinity preference behaviour in the estuary and ocean outmigration stages, but not at lake-exit. Our results suggest that smolt physiological condition upon reaching the estuary could influence migratory behaviour and habitat selection. This provides evidence on the temporally dependent interplay of physiology, behaviour and migration in wild juvenile Pacific salmon, with juvenile rearing conditions influencing smolt energetic status, which in turn influences habitat choice during downstream migration. The implication for the conservation of migratory species is that the relative importance of stopover habitats may vary as a function of initial condition.

Management of antipsychotics in primary care: Insights from healthcare professionals and policy makers in the United Kingdom.

INTRODUCTION: Antipsychotic medication is increasingly prescribed to patients with serious mental illness. Patients with serious mental illness often have cardiovascular and metabolic comorbidities, and antipsychotics independently increase the risk of cardiometabolic disease. Despite this, many patients prescribed antipsychotics are discharged to primary care without planned psychiatric review. We explore perceptions of healthcare professionals and managers/directors of policy regarding reasons for increasing prevalence and management of antipsychotics in primary care. METHODS: Qualitative study using semi-structured interviews with 11 general practitioners (GPs), 8 psychiatrists, and 11 managers/directors of policy in the United Kingdom. Data was analysed using thematic analysis. RESULTS: Respondents reported competency gaps that impaired ability to manage patients prescribed antipsychotic medications, arising from inadequate postgraduate training and professional development. GPs lacked confidence to manage antipsychotic medications alone; psychiatrists lacked skills to address cardiometabolic risks and did not perceive this as their role. Communication barriers, lack of integrated care records, limited psychology provision, lowered expectation towards patients with serious mental illness by professionals, and pressure to discharge from hospital resulted in patients in primary care becoming 'trapped' on antipsychotics, inhibiting opportunities to deprescribe. Organisational and contractual barriers between services exacerbate this risk, with socioeconomic deprivation and lack of access to non-pharmacological interventions driving overprescribing. Professionals voiced fears of censure if a catastrophic event occurred after stopping an antipsychotic. Facilitators to overcome these barriers were suggested. CONCLUSIONS: People prescribed antipsychotics experience a fragmented health system and suboptimal care. Several interventions could be taken to improve care for this population, but inadequate availability of non-pharmacological interventions and socioeconomic factors increasing mental distress need policy change to improve outcomes. The role of professionals' fear of medicolegal or regulatory censure inhibiting antipsychotic deprescribing was a new finding in this study.

Unpaid carers' experiences of supporting people with dementia to use social media.

Objectives: The aim of this study was to explore unpaid carers' experiences of supporting people with dementia to use social media.Methods: Unpaid carers (n = 234) responded to an online survey about their attitudes towards people with dementia using social media and any experiences supporting this usage. Responses to closed questions were analysed using frequency analysis; qualitative data were analysed thematically.Results: Fifty-five carers (23.5%) cared for someone with dementia who used social media. Thematic analysis produced four themes: (1) carers as social media navigators; (2) social media supports care; (3) carers as social media guardians; and (4) labour-intensive work. Carers valued the social connectivity and stimulation social media provided but remained vigilant about online safety. They carefully managed the online experiences of people with dementia, balancing perceived benefits with safety, security, and caring demands.Conclusions: These findings shed light on the complexities of caring in the digital age. Many carers are supporting people with dementia in using social media, but there is little guidance on how best to do this. As older adults continue to embrace social media, carers, support organisations, and policymakers must adapt and work with technology developers to ensure safe and supportive online experiences.

'I'd be lost without my smartphone': a qualitative analysis of the use of smartphones and tablets by people living with dementia, mild cognitive impairment, and their caregivers.

OBJECTIVES: Smartphone and tablet devices appear to offer some benefits for enhancing the quality of life of people living with dementia, especially enabling them to stay independent and socially engaged in the early stages of the disease. However, there remains a need to understand the ways that these devices may enhance the lived experience of people living with dementia, mild cognitive impairment, and their caregivers. METHODS: We interviewed 29 people living with dementia, mild cognitive impairment, and their caregivers to explore their experiences of and attitudes towards smartphones and tablets. RESULTS: We generated three main themes: smart devices in practice as a person living with cognitive impairment; living in a digital world, and smart devices as appropriate and easily accessible support for everyday living. Smart devices were seen as valuable, versatile tools to complete essential and meaningful activities, and as necessary devices to participate in modern life. There was a strong desire for greater support to learn to use smart devices to facilitate living well with cognitive impairment. CONCLUSION: The lived experience of people living with dementia and mild cognitive impairment emphasises the central role of smart devices in their lives, and the need for research to move beyond rehearsal of what is needed to co-production and evaluation of smart technology-based educational interventions.

Viscoelastometry to Manage Bleeding in Liver Disease.

A state of "re-balanced haemostasis" describes complex coagulation changes that arise in patients with liver disease. Changes include alterations in procoagulant and anticoagulant proteins, platelets and von Willebrand factor, as well as the fibrinolytic system. Various circumstances including infection, trauma, or surgery may disrupt this balance and predispose an individual to bleeding or thrombosis. The prothrombin time, international normalised ratio, and activated partial thromboplastin time are conventional coagulation screening tests that are routinely employed by clinicians to investigate unexplained bleeding, monitor anticoagulation, and inform preoperative assessments of bleeding risk. These standard coagulation tests assess quantitative defects in procoagulant clotting factors and are insensitive to levels of natural anticoagulants, which together with procoagulant factors, are often perturbed in liver disease. Therefore, the prolongation of clotting times measured by these tests often does not reflect the multifaceted alterations of haemostasis in these patients. Viscoelastic testing (VET) provides a more encompassing assessment of clotting function by recording real-time viscoelastic changes in whole blood and includes parameters that provide information on coagulation factor function, platelet contribution to clot formation, as well as fibrinolysis. To date, VET has been employed to predict and inform transfusion support in obstetric, trauma, and cardiac surgical fields, and its use in patients undergoing liver transplantation is well established. The ability of VET to accurately predict bleeding risk and precisely guide transfusion algorithms for patients with liver disease undergoing other invasive procedures or experiencing bleeding complications has been the topic of research over the last decade. This review is a critical summary of this data and provides a detailed snapshot of the position of VET as a clinical tool in patients with liver disease.

Estimating phenology and phenological shifts with hierarchical modeling.

Climate-driven changes to phenology are some of the most prevalent climate change impacts, yet there is no commonly accepted approach to modeling phenological shifts. Here, we present a hierarchical modeling framework for estimating intra-annual patterns in phenology (e.g., peak phenological expression) and analyzing interannual rates of change in peak phenology. Our approach allows for the estimation of multiple sources of uncertainty, including observation error (e.g., imperfect observations of intra-annual patterns in phenology like peak flowering date) and variation in phenological processes (e.g., uncertainty in the rate of change in annual peak phenological expression). Covariates may be included as predictors of annual peaks or interannual variability in phenological responses. We demonstrate the use of our hierarchical modeling framework in two migratory species-juvenile chum salmon and Swainson's thrush. We acknowledge that the complexity of hierarchical models can be difficult to implement from scratch and present an R package that can be used to model peak dates and range (number of days between 25th- and 75th-quartile dates), as well as a rate of change in peak phenology. Increasing precision, calculating uncertainty, and allowing for imperfect data sets when estimating phenological shifts should help ecologists understand how organisms respond to climate change.

The role of spatial structure in at-risk metapopulation recoveries.

Metapopulations are often managed as a single contiguous population despite the spatial structure underlying their local and regional dynamics. Disturbances from human activities can also be spatially structured with mortality impacts concentrated to just a few local populations among the aggregate. Scale transitions between local and regional processes can generate emergent properties whereby the whole system can fail to recover as quickly as expected for an equivalent single population. Here, we draw on theory and empirical case studies to ask: what is the consequence of spatially structured ecological and disturbance processes on metapopulation recoveries? We suggest that exploring this question could help address knowledge gaps for managing metapopulations including: Why do some metapopulations recover quickly while others remain collapsed? And, what risks are unaccounted for when metapopulations are managed at aggregate scales? First, we used model simulations to examine how scale transitions among ecological and disturbance conditions interact to generate emergent metapopulation recovery outcomes. In general, we found that the spatial structure of disturbance was a strong determinant of recovery outcomes. Specifically, disturbances that unevenly impacted local populations consistently generated the slowest recoveries and highest conservation risks. Ecological conditions that dampened metapopulation recoveries included low dispersal, variable local demography, sparsely connected habitat networks, and spatially and temporally correlated stochastic processes. Second, we illustrate the unexpected challenges of managing metapopulations by examining the recoveries of three USA federally listed endangered species: Florida Everglade snail kites, California and Alaska sea otters, and Snake River Chinook salmon. Overall, our results show the pivotal role of spatial structure in metapopulation recoveries whereby the interplay between local and regional processes shapes the resilience of the whole system. With this understanding, we provide guidelines for resource managers tasked with conserving and managing metapopulations and identify opportunities for research to support the application of metapopulation theory to real-world challenges.

Phenological shifts and mismatch with marine productivity vary among Pacific salmon species and populations.

Global climate change is shifting the timing of life-cycle events, sometimes resulting in phenological mismatches between predators and prey. Phenological shifts and subsequent mismatches may be consistent across populations, or they could vary unpredictably across populations within the same species. For anadromous Pacific salmon (Oncorhynchus spp.), juveniles from thousands of locally adapted populations migrate from diverse freshwater habitats to the Pacific Ocean every year. Both the timing of freshwater migration and ocean arrival, relative to nearshore prey (phenological match/mismatch), can control marine survival and population dynamics. Here we examined phenological change of 66 populations across six anadromous Pacific salmon species throughout their range in western North America with the longest time series spanning 1951-2019. We show that different salmon species have different rates of phenological change but that there was substantial within-species variation that was not correlated with changing environmental conditions or geographic patterns. Moreover, outmigration phenologies have not tracked shifts in the timing of marine primary productivity, potentially increasing the frequency of future phenological mismatches. Understanding population responses to mismatches with prey are an important part of characterizing overall population-specific climate vulnerability.

Characterization of methylation profiles in spontaneous preterm birth placental villous tissue.

Preterm birth is a global public health crisis which results in significant neonatal and maternal mortality. Yet little is known regarding the molecular mechanisms of idiopathic spontaneous preterm birth, and we have few diagnostic markers for adequate assessment of placental development and function. Previous studies of placental pathology and our transcriptomics studies suggest a role for placental maturity in idiopathic spontaneous preterm birth. It is known that placental DNA methylation changes over gestation. We hypothesized that if placental hypermaturity is present in our samples, we would observe a unique idiopathic spontaneous preterm birth DNA methylation profile potentially driving the gene expression differences we previously identified in our placental samples. Our results indicate the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern suggesting hypermaturity. Only seven significant differentially methylated regions fitting the idiopathic spontaneous preterm birth specific (relative to the controls) profile were identified, indicating unusually high similarity in DNA methylation between idiopathic spontaneous preterm birth and term birth samples. We identified an additional 1,718 significantly methylated regions in our gestational age matched controls where the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern, again indicating a striking level of similarity between the idiopathic spontaneous preterm birth and term birth samples. Pathway analysis of these regions revealed differences in genes within the WNT and Cadherin signaling pathways, both of which are essential in placental development and maturation. Taken together, these data demonstrate that the idiopathic spontaneous preterm birth samples display a hypermature methylation signature than expected given their respective gestational age which likely impacts birth timing.

Exposure to thin and non-thin bodies elicits 'feeling fat': Validation of a novel state measure.

'Feeling fat' refers to the subjective experience of carrying excess weight and relates to severity of eating pathology. Despite research suggesting that 'feeling fat' fluctuates across contexts, this construct is almost exclusively assessed in terms of frequency or as a trait. Examining state 'feeling fat' in response to external stimuli can inform us of the nature of this construct. In an experimental study, 290 community women were exposed to five categories of affective (pleasant, aversive, and neutral) and body (thin and non-thin) images in quasi-random order. Self-Assessment Manikin (SAM) valence and arousal rating scales as well as a novel SAM 'feeling fat' scale were rated for each image. Theoretically-relevant constructs (i.e., trait 'feeling fat', thin-ideal internalization, body dissatisfaction, eating pathology) were also measured. Body images elicited greater state 'feeling fat' than affective images, with images of non-thin bodies producing higher state 'feeling fat' than thin bodies. Positive correlations were observed between state 'feeling fat' in response to thin and all variables of interest, whereas associations between these variables and 'feeling fat' in response to non-thin images were small or non-significant. The development of a state measure of 'feeling fat' allows for the investigation of triggers of this bodily experience and will facilitate future research.

Occupational exposure to respirable crystalline silica among US metal and nonmetal miners, 2000-2019.

BACKGROUND: In metal and nonmetal (M/NM) mines in the United States, respirable crystalline silica (RCS) exposures are a recognized health hazard and a leading indicator of respiratory disease. This study describes hazardous exposures that exceed occupational exposure limits and examines patterns of hazardous RCS exposure over time among M/NM miners to better inform the need for interventions. METHODS: Data for this study were obtained from the Mine Safety and Health Administration (MSHA) Open Government Initiative Portal for the years 2000-2019, examining respirable dust samples with MSHA-measured quartz concentration >1%. Descriptive statistics for RCS were analyzed for M/NM miners by year, mine type, sector, commodity, occupation, and location in a mine. RESULTS: This study found the overall geometric mean (GM) for personal exposures to RCS was 28.9 µg/m3 (geometric standard deviation: 2.5). Exposures varied significantly by year, mine type, sector, commodity, occupation, and location in a mine. Overall, the percentages of exposures above the MSHA permissible exposure limit (PEL for respirable dust with >1% quartz, approximately 100 µg/m3 RCS) and the National Institute for Occupational Safety and Health RCS recommended exposure limit (REL, 50 µg/m3 ) were 11.8% and 27.3%, respectively. GM exposures to RCS in 2018 (45.9 µg/m3 ) and 2019 (52.9 µg/m3 ) were significantly higher than the GM for all years prior. The overall 95th percentile of RCS exposures from 2000 to 2019 was 148.9 µg/m3 , suggesting a substantial risk of hazardous exposures above the PEL and REL during the entire period analyzed. CONCLUSIONS: The prevalence of high exposures to RCS among M/NM miners continues in the past 20 years and may be increasing in certain settings and occupations. Further research and intervention of the highest exposures are needed to minimize the risks of acquiring silica-induced respiratory diseases.

Influence of Single Dose Enrofloxacin Injection on Development of Fluoroquinolone Resistance in Campylobacter jejuni in Calves.

Fluoroquinolone (FQ) resistance in a major foodborne bacterial pathogen, Campylobacter jejuni, derived from cattle has recently become prevalent and poses a significant public health concern. However, the underlying factors for this increase are not entirely clear. To evaluate the effect of enrofloxacin treatment on FQ-resistance development in C. jejuni, 35 commercial calves were equally divided into five groups (Groups 1-5) and were orally inoculated with FQ-susceptible (FQ-S) C. jejuni. Eight days later, Groups 4 and 5 were challenged with Mannheimia haemolytica via a transtracheal route to induce a respiratory disease; after 8 days, Groups 2, 3, 4, and 5 were injected subcutaneously with enrofloxacin (7.5 mg/kg for Groups 2 and 4, and 12.5 mg/kg for Groups 3 and 5). Colonization levels by FQ-resistant (FQ-R) and FQ-S Campylobacter in rectal feces were determined via differential culture throughout the experiment. Before oral inoculation with C. jejuni, only five calves were naturally colonized by Campylobacter, four of which were also colonized by FQ-R C. jejuni (three in Group 1 and one in Group 3). Soon after the oral inoculation, almost all calves in the groups became stably colonized by FQ-S C. jejuni (~3-6 log10 CFU/g), except that the four calves that were pre-colonized before inoculation remained positive with both FQ-R and FQ-S C. jejuni. Following enrofloxacin administration, C. jejuni colonization declined sharply and rapidly in all treated groups to undetectable levels; however, the vast majority of the animals were recolonized by C. jejuni at comparable levels 72 h after the treatment. Notably, no FQ-R C. jejuni was detected in any of the calves that received enrofloxacin, regardless of the drug dose used or disease status of the animals. The lack of detection of FQ-R C. jejuni was likely due to the localized high concentration of the antibiotic in the intestine, which may have prevented the emergence of the FQ-R mutant. These findings indicate that single-dose enrofloxacin use in cattle poses a low risk for selection of de novo FQ-R mutants in C. jejuni.

Sensitive and reproducible cell-free methylome quantification with synthetic spike-in controls.

Cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) identifies genomic regions with DNA methylation, using a protocol adapted to work with low-input DNA samples and with cell-free DNA (cfDNA). We developed a set of synthetic spike-in DNA controls for cfMeDIP-seq to provide a simple and inexpensive reference for quantitative normalization. We designed 54 DNA fragments with combinations of methylation status (methylated and unmethylated), fragment length (80 bp, 160 bp, 320 bp), G + C content (35%, 50%, 65%), and fraction of CpG dinucleotides within the fragment (1/80 bp, 1/40 bp, 1/20 bp). Using 0.01 ng of spike-in controls enables training a generalized linear model that absolutely quantifies methylated cfDNA in MeDIP-seq experiments. It mitigates batch effects and corrects for biases in enrichment due to known biophysical properties of DNA fragments and other technical biases.

Examining relationships among thin-ideal internalization, eating pathology, and motivational reactions to high- and low-calorie food.

Motivational responses to food stimuli are relevant for eating disorders (EDs). Research examining reactions to food in EDs has been mixed, with some studies reporting enhanced appetitive responses, and others observing defensive responses, to food. Thin-ideal internalization, a socio-cognitive factor implicated in EDs, may relate to these mixed findings, as individuals with eating pathology may experience food as a threat to internalized ideals of thinness, despite its inherently appetitive qualities. In the present study, physiological reflexes measuring defensive (startle blink reflex) and appetitive (postauricular reflex) responding as well as self-report ratings were recorded while 88 women with and without eating pathology viewed images of high- and low-calorie food. Greater global eating pathology, but not thin-ideal internalization, was associated with negative self-report valence ratings and lower craving ratings of high-calorie food. In contrast, greater thin-ideal internalization and eating pathology both related to more positive self-report valence ratings of low-calorie food, with thin-ideal internalization accounting for some of the shared variance between low-calorie food ratings and eating pathology. Overall, thin-ideal internalization may represent a higher-order factor that may contribute to the relationship between conscious reactions to food and disordered eating.

A Systematic Review of Smartphone and Tablet Use by Older Adults With and Without Cognitive Impairment.

BACKGROUND AND OBJECTIVES: A systematic review was conducted to explore the use of smartphones and tablet computers as cognitive and memory aids by older adults with and without cognitive impairment, specifically the effects of smartphone and tablet use on participants' cognition and memory, and the barriers and facilitators to smartphone and tablet use for cognitive and memory support. RESEARCH DESIGN AND METHODS: A systematic search of 6 key databases found 11,895 citations published between 2010 and 2021. Studies were included if they involved community-dwelling older adults with or without cognitive impairment arising from acquired brain injury, mild cognitive impairment, or dementia, and if they evaluated everyday smartphone or tablet device use for cognition, memory, or activities of daily living. RESULTS: A total of 28 papers were included in the narrative synthesis. There was some evidence that the use of smartphones and tablets could aid cognitive function in older adults without cognitive impairment, particularly executive function and processing speed. There was modest evidence that smartphone and tablet use could support memory in both older adults without cognitive impairment and those with acquired brain injury and dementia. DISCUSSION AND IMPLICATIONS: Smartphones and tablets were seen by users as acceptable, enjoyable, and nonstigmatizing alternatives to conventional assistive technology devices; however, current use of smartphone and tablet devices is hindered by the digital literacy of older adults, a lack of accommodation for older adult users' motor and sensory impairments, and a lack of input from clinicians and researchers. Much of the evidence presented in this review derives from case studies and small-scale trials of smartphone and tablet training interventions. Further research is needed into older adults' use of smartphones and tablets for cognitive support before and after the onset of cognitive impairment in order to develop effective evidence-based smart technology cognition and memory aids.

Tissue engineering of the retina: from organoids to microfluidic chips.

Despite advancements in tissue engineering, challenges remain for fabricating functional tissues that incorporate essential features including vasculature and complex cellular organisation. Monitoring of engineered tissues also raises difficulties, particularly when cell population maturity is inherent to function. Microfluidic, or lab-on-a-chip, platforms address the complexity issues of conventional 3D models regarding cell numbers and functional connectivity. Regulation of biochemical/biomechanical conditions can create dynamic structures, providing microenvironments that permit tissue formation while quantifying biological processes at a single cell level. Retinal organoids provide relevant cell numbers to mimic in vivo spatiotemporal development, where conventional culture approaches fail. Modern bio-fabrication techniques allow for retinal organoids to be combined with microfluidic devices to create anato-physiologically accurate structures or 'retina-on-a-chip' devices that could revolution ocular sciences. Here we present a focussed review of retinal tissue engineering, examining the challenges and how some of these have been overcome using organoids, microfluidics, and bioprinting technologies.

Limits on performance and survival of juvenile sockeye salmon (Oncorhynchus nerka) during food deprivation: a laboratory-based study.

Long-distance migrations can be energetically demanding and can represent phases of high mortality. Understanding relationships between body condition and migratory performance can help illuminate the challenges and vulnerabilities of migratory species. Juvenile anadromous sockeye salmon (Oncorhynchus nerka) may migrate over 1000 km from their freshwater nursery habitats to estuary and ocean feeding grounds. During the period corresponding to the seaward migration of sockeye salmon, we held smolts in the laboratory to ask the following: (i) Does non-feeding migration duration influence prolonged swim performance and survival? (ii) What are the relationships between individual body condition and swim performance and survival? Wild sockeye salmon were intercepted during their migration and held without food for up to 61 days to represent the non-feeding freshwater migration and the extremes of poor estuary habitat. We conducted 40 sets of prolonged swim trials on 319 fish from 3 treatment groups that represented entrance to the marine environment on (i) an average,(ii) a delayed and (iii) a severely delayed migration schedule. Experimentally controlled freshwater migration duration did not impact swim performance or survival. Swim performance decreased concomitant with condition factor, where smolts with a Fulton's condition factor of <0.69 were less likely (<50% probability) to complete the swim test (90 min swim test, at ~0.50 m/s). Survival of salmon smolts in the laboratory was less likely at energy densities of less than 3.47 MJ/kg. Swim performance decreased much sooner than survival, suggesting that swim performance, and therefore condition factor, may be a good indicator of survival of migratory smolts, as fish with reduced swim performance will likely be predated. These two relationships, one more ecologically relevant and one more clinical, help reveal the limits of long-distance migration for juvenile salmon and can be used to determine population-specific starvation risk associated with various freshwater and marine habitat conditions.

The Use of Platelet-Rich Plasma (PRP) for the Management of Non-union Fractures.

PURPOSE OF REVIEW: The treatment of non-union fractures represents a significant challenge for orthopaedic surgeons. In recent years, biologic agents have been investigated and utilised to support and improve bone healing. Among these agents, platelet-rich plasma (PRP) is an emerging strategy that is gaining popularity. The aim of this review is to evaluate the current literature regarding the application and clinical effectiveness of PRP injections, specifically for the treatment of non-union fractures. RECENT FINDINGS: The majority of published studies reported that PRP accelerated fracture healing; however, this evidence was predominantly level IV. The lack of randomised, clinical trials (level I-II evidence) is currently hampering the successful clinical translation of PRP as a therapy for non-union fractures. This is despite the positive reports regarding its potential to heal non-union fractures, when used in isolation or in combination with other forms of treatment. Future recommendations to facilitate clinical translation and acceptance of PRP as a therapy include the need to investigate the effects of administering higher volumes of PRP (i.e. 5-20 mL) along with the requirement for more prolonged (> 11 months) randomised clinical trials.