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Aim: Autologous haematopoietic stem cell transplant (HSCT) is an effective treatment for people with highly-active relapsing multiple sclerosis (MS), who are not adequately responding to disease-modifying therapies. To date, research has predominantly focused on disease-specific outcome measures. There is a lack of research exploring patient experiences of this complex treatment. The study aims to explore the experience of considering and receiving HSCT treatment for MS., Methods: Semi-structured interviews were conducted online with 12 adults with MS who had undergone HSCT treatment. Interview topics covered the experience of deciding on the treatment, the HSCT process itself, and the patient-reported outcomes following HSCT. Interviews were audio-recorded and transcribed verbatim. A thematic analysis approach was employed., Results: Three main themes were identified: (1) Balancing hope and fear explores the decision-making experience when considering HSCT as a treatment; (2) Distinct emotional experience, highlights the unique challenges faced on all stages of the treatment journey; and (3) Adjusting to outcomes, explores how participants make sense of the aftermath of the treatment, including managing the ongoing uncertainty of MS and complications arising from HSCT., Discussion: HSCT is a complex treatment, both physically and psychologically for pwMS. A comprehensive and holistic care pathway is required to support people with MS at all stages of the treatment process, to ensure patient-centred planning and care., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Autologous haematopoietic stem cell transplant (HSCT) is considered an effective treatment for highly active multiple sclerosis (MS). To date, most research has focused primarily on disease outcome measures, despite the significant impact of neuropsychological symptoms on MS patients' quality of life. The current systematic review aimed to examine whether HSCT for MS impacts neuropsychological outcome measures such as cognition, fatigue, mood, and quality of life., Methods: The review was registered with the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42023474214). Systematic searches were carried out in six databases (PsycINFO, PubMed, Embase, Scopus, CINAHL and Web of Science) based on the following inclusion criteria: (i) published in peer-reviewed journals in English; (ii) longitudinal studies of adults with MS (iii) at least one neuropsychological outcome was assessed pre- and post-HSCT using standardised measures. Risk of bias was assessed using the National Heart, Lung and Blood Institute (NHLBI) quality assessment tools. A narrative synthesis was used to present results., Results: Eleven studies were included in the review. Long-term improvements in quality of life post-HSCT were identified. In terms of cognition and fatigue, the evidence was mixed, with some post-HSCT improvements identified. Decline in cognitive performance in the short-term post-HSCT was observed. No changes in mood were identified post-HSCT. Arguments for interpreting these results with caution are presented based on risk of bias. Arguments for interpreting these results with caution are presented based on risk of bias. Limitations of the evidence are discussed, such confounding variables and lack of statistical power., Conclusion: The evidence base for the impact of HSCT for MS on neuropsychological outcomes is limited. Further research is required to progress understanding to facilitate clinician and patient understanding of HSCT treatment for MS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No known declarations of interest to state., (Copyright © 2024. Published by Elsevier B.V.)

Background: People with MS (pwMS) commonly experience a range of hidden symptoms, including cognitive impairment, anxiety and depression, fatigue, pain, and sensory difficulties. These "invisible" symptoms can significantly impact wellbeing, relationships, employment and life goals. We developed a novel bespoke online group neuropsychological intervention combining psychoeducation and cognitive rehabilitation with an Acceptance and Commitment Therapy (ACT)-informed approach for pwMS in an acute tertiary hospital. This 'Neuropsychological Intervention for Managing Invisible Symptoms' in MS (NIMIS-MS) consisted of 6 sessions, each with a psychoeducation and ACT component. The content included psychoeducation around managing cognitive difficulties, fatigue, pain, sleep and other unpleasant sensations in MS with the general approach of understanding, monitoring, and recognising patterns and potential triggers. Specific cognitive rehabilitation and fatigue management strategies were introduced. The ACT-informed component focussed on three core ACT areas of the 'Triflex' of psychological flexibility (Harris, 2019): Being Present, Opening Up, and Doing What Matters., Methods: 118 pwMS attended the NIMIS-MS group intervention which was delivered 14 times in six-week blocks over an 18-month period. To evaluate the effectiveness and acceptability, participants completed measures of depression and anxiety (HADS), functional impairment (WSAS), Values- Progress (VQ) and Values- Obstruction (VQ), and Acceptance of MS (MSAS) pre and post NIMIs-MS group intervention. Qualitative feedback was obtained during focus groups after the final session and via online feedback questionnaires RESULTS: Pre-post analysis showed that symptoms of depression and anxiety were significantly lower and acceptance of MS was significantly higher following completion of the NIMIS-MS group. Qualitative feedback showed that participants reported that they felt more equipped to manage the "invisible" symptoms of MS following completion of the group, and benefited from using ACT-based strategies and techniques. Participants highly valued the peer support that evolved during the NIMIS-MS groups. The online format was considered more accessible than in-person groups, due to less concerns of travel time, cost, fatigue, and comfort and infection., Conclusion: Evaluation suggests that our novel NIMIS-MS groups is an acceptable, beneficial and feasible approach for providing neuropsychological interventions to individuals with MS., Competing Interests: Declaration of competing interest The authors do not have any competing or conflicting interests to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Hospitalized pediatric patients with behavioral health (BH) diagnoses awaiting transfer can exhibit behaviors that may lead to workplace violence such as aggression. Workplace violence can lead to discomfort in caring for these patients. Huddles can be used as a tool to identify potential for violence, to help address workplace violence, and improve clinician situational awareness., Methods: Utilizing QI methodology, a BH specific huddle tool was created and implemented on an Acute Care floor that identified key components such as triggers and behavioral stability. Mixed methods were used to study the intervention including focus groups, surveys and measurement of agreement (surrogate for situational awareness). The aims of this quality improvement (QI) project were to 1) improve situational awareness by increasing agreement between team members 2) improve the overall comfort of the clinical team caring for BH patients by 10%., Results: Agreement between clinicians on patient stability increased by 20%. Comfort in caring for BH patients increased by 4%. Providers reported the tool increased their understanding (89%) and communication (81%) regarding plan of care., Application to Practice: Standardized huddle tool can be utilized to increase situational awareness among team members caring for patients with behavioral health diagnoses and may help to address workplace violence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Most prostate cancers are adenocarcinomas. However, there is a rare and aggressive subtype known as small cell carcinoma of the prostate (SCCP). This variant of prostate cancer is marked by its distinctive features, including high-grade malignancy, neuroendocrine differentiation, and a unique clinical presentation, often involving metastases. This report details the presentation and management of a 66-year-old African-American male who was originally diagnosed with high-risk adenocarcinoma of the prostate. At initial diagnosis, the patient was suboptimally treated with radiation alone without androgen deprivation therapy (ADT). On re-biopsy several years later, he was found to have localized recurrent disease with transformation into SCCP. The prognosis for SCCP is poor with a mean survival. Patients typically present with metastases, commonly to the brain, liver, bones, or bladder. SCCP after treatment for adenocarcinoma of the prostate is more common than de novo presentation. The amount of neuroendocrine differentiation of SCCP often increases with treatment, particularly after treatment with ADT. This report emphasizes the importance of timely and optimal care when treating prostate cancer and suggests potential consequences that inappropriate treatment or treatment delays may entail., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Eckrich et al.)

Birds nesting on riverine beaches are exposed to large temperature fluctuations, while changing water levels pose flooding risks. We used miniature temperature loggers ( i Buttons®) placed in nests and on the beach surface combined with time-lapse photography to study incubation behaviour in the black skimmer ( Rynchops niger ) on the Manu River, Peru. Since the species exhibits sexual size dimorphism, we could identify partner switches in images and the contribution to incubation effort by each pair member. Results of the study documented that nest temperature was less affected by ambient temperature and fluctuated less than the surroundings. Despite shorter incubation bouts at midday, black skimmers maintained a close to constant presence at the nest by more frequent nest exchanges. In fact, while female black skimmers generally incubated more and for longer than males, pairs shared incubation most consistently during the hottest part of the day. Incubation probability decreased around dusk, a peak foraging time for the species and a time when beach temperature overlapped with nest temperature. A biparental incubation strategy across the diel cycle appears to allow black skimmers breeding at the Manu River to incubate in challenging thermal conditions, but further studies are needed to determine proximity to thermal limits., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Existing literature illustrates a high prevalence of child protection issues throughout Kenya. This is adjoined by additional research detailing issues of corruption, cultural rationalization and the potential lack of capability to deal with the problem in existing law enforcement practices. There is no specific research that investigates the establishment or operational function of a child protection department within law enforcement in Kenya., Objective: This study aims to directly address this research gap by exploring the establishment of an overseas initiative to support the development of a child protection function in the National Police Service of Kenya and to analyse the conditions in developing the project., Participants, Setting and Methods: The study, which took place in Kenya, consists of n = 15 face to face interviews, comprising of n = 10 Kenyan Police Child Protection Officers, and n = 5 National Crime Agency (NCA) officers who contributed to the development of the unit. The semi-structured interviews were based upon existing literature from developing overseas support and child protection in Kenya., Conclusion: The results evidenced the need to focus in three key areas when building child protection capability overseas to create a successful function; the requirement to tailor context specific understanding of the culture and operating environment, the need to understand the current and potential capabilities within this context, and the importance of obtaining leadership and governance support from appropriate stakeholders both internally and externally. These themes begin to develop a base for the development of international practice for the establishment of overseas child protection policing functions., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Macrophage activation syndrome is a life-threatening syndrome of uncontrolled immune activation with variable clinical presentation making early diagnosis difficult. It is often manifested by the development of multi-organ failure due to systemic inflammatory response. Patients with ulcerative colitis (UC) on purine antimetabolites are at high risk for severe myelosuppression due to the mechanism of thiopurine toxicity which potentially contributes to the development of macrophage activation syndrome. We present a case of a 39-year-old woman with a 2-year history of UC previously treated with 6-mercaptopurine (6-MP) and recent COVID-19 infection, who was admitted to our emergency department for C. difficile infection and subsequently developed macrophage activation syndrome. This case report also raises the question of whether abrupt discontinuation of 6-MP may have contributed to the worsening of the patient's symptoms of underlying hemophagocytic lymphohistiocytosis (HLH) and her rapid deterioration. Both macrophage activation syndrome and COVID-19 infection can produce a large number of pro-inflammatory cytokines termed "cytokine storm," but a pro-inflammatory cytokine panel breakdown helps to differentiate between the two. Our case report emphasizes the importance of close monitoring of patients on purine antimetabolite therapy who present with signs and symptoms of systemic toxicity.

Single nucleotide polymorphisms (SNPs) can be analysed for identity or kinship applications in forensic genetics to either provide an adjunct to traditional STR typing or as a stand-alone approach. The advent of massively parallel sequencing technology (MPS) has provided a useful opportunity to more easily deploy SNP typing in a forensic context, given the ability to simultaneously amplify a large number of markers. Furthermore, MPS also provides valuable sequence data for the targeted regions, which enables the detection of any additional variation seen in the flanking regions of amplicons. In this study we genotyped 977 samples across five UK-relevant population groups (White British, East Asian, South Asian, North-East African and West African) for 94 identity-informative SNP markers using the ForenSeq DNA Signature Prep Kit. Examination of flanking region variation allowed for the identification of 158 additional alleles across all populations studied. Here we present allele frequencies for all 94 identity-informative SNPs, both including and excluding the flanking region sequence of these markers. We also present information on the configuration of these SNPs in the ForenSeq DNA Signature Prep Kit, including performance metrics for the markers and investigation of bioinformatic and chemistry-based discordances. Overall, the inclusion of flanking region variation in the analysing workflow for these markers reduced the average combined match probability 2175 times across all populations, with a maximum reduction of 675,000-fold in the West African population. The gain due to flanking region-based discrimination increased the heterozygosity of some loci above that of some of the least useful forensic STR loci; thus demonstrating the benefit of enhanced analysis of currently targeted SNP markers for forensic applications., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laurence Devesse is a current employee of Verogen, who manufacture the kit used in this study. At the time of data collection she was a PhD student at King’s College London, and has had no part in writing the manuscript since joining Verogen., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Impairments in speech and social cognition have been reported in people with multiple sclerosis (pwMS), although their relationships with neuropsychological outcomes and their clinical utility in MS are unclear., Objectives: To evaluate word finding, prosody and social cognition in pwMS relative to healthy controls (HC)., Methods: We recruited people with relapsing MS (RMS, n = 21), progressive MS (PMS, n = 24) and HC (n = 25) from an outpatient MS clinic. Participants completed a battery of word-finding, social cognitive, neuropsychological and clinical assessments and performed a speech task for prosodic analysis., Results: Of 45 pwMS, mean (SD) age was 49.4 (9.4) years, and median (range) Expanded Disability Severity Scale score was 3.5 (1.0-6.5). Compared with HC, pwMS were older and had slower information processing speed (measured with the Symbol Digit Modalities Test, SDMT) and higher depression scores. Most speech and social cognitive measures were associated with information processing speed but not with depression. Unlike speech, social cognition consistently correlated with intelligence and memory. Visual naming test mean response time (VNT-MRT) demonstrated worse outcomes in MS versus HC (p = .034, Nagelkerke's R 2  = 65.0%), and in PMS versus RMS (p = .009, Nagelkerke's R 2  = 50.2%). Rapid automatised object naming demonstrated worse outcomes in MS versus HC (p = .014, Nagelkerke's R 2  = 49.1%). These word-finding measures showed larger effect sizes than that of the SDMT (MS vs. HC, p = .010, Nagelkerke's R 2  = 40.6%; PMS vs. RMS, p = .023, Nagelkerke's R 2  = 43.5%). Prosody and social cognition did not differ between MS and HC., Conclusions: Word finding, prosody and social cognition in MS are associated with information processing speed and largely independent of mood. Impairment in visual object meaning perception is potentially a unique MS disease-related deficit that could be further explored and cautiously considered as an adjunct disability metric for MS., (© 2022 The British Psychological Society.)

Background: There is evidence that subjective fatigue can influence cognitive functioning in multiple sclerosis (MS). DeLuca et al.'s (2004) Relative Consequence Model proposes that impairments to other high-level cognitive functions, such as memory, result from the disease's effect on information processing speed., Objective: The primary aims of the study were to investigate both 1) the relationship between subjective fatigue and cognitive functioning, as measured by the widely used Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in MS; and 2) the consequential effect of fatigue on information processing speed as predicted by the Relative Consequence Model., Methods: 192 participants with MS attending tertiary referral MS centre completed the Modified Fatigue Impact Scale and BICAMS., Results: Multiple correlation analyses determined that there were statistically significant relationships between all domains assessed by the BICAMS and levels of fatigue, such that higher levels of self-reported fatigue were associated with lower performance on information-processing, and visual and verbal learning. After controlling for information processing speed, the strength of correlation between fatigue and learning performance weakened. Linear regression analysis showed that fatigue predicted the most variance in verbal learning and 11.7% of the overall variance in BICAMS performance., Conclusion: Subjective fatigue and objective cognitive performance in MS are related. Caution is advised in the interpretation of BICAMS scores in cases where high levels of fatigue are present, and more detailed neuropsychological assessments may be required in order to accurately identify objective cognitive impairment independent of subjective fatigue., Competing Interests: Declaration of Competing Interest SMY received funding for research from Novaritis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Understanding the effect of heat on skin cells is important for the prevention of burn injury. Knowledge of the heat dose required to kill cells can be used to study the cellular mechanisms involved in thermal injury cell death, to assist with the development of novel burn treatments. In this study, primary human skin dermal fibroblasts were exposed to temperatures from 37 to 54 °C for 1 h and the relative cell viability of heat-treated and control cells was assessed. Cell damage and viability were assessed by light microscopy, MTT assay and live/dead staining. The LD50 for 1 h of heat exposure was 48 °C for primary fibroblasts; and there was evidence that thermal damage to cells begins to occur at 43 °C. This study presents a reproducible method for examining the effect of heat on primary human cells grown in culture on a cellular level and can be used in the future to study the mechanisms behind heat-induced cell death, to inform burn injury prevention efforts and effective post-burn treatment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Discrepancies between subjective cognitive difficulties and objective measures of cognitive function in people with MS have been identified and may be related to mood and fatigue. The aim of the present study was to examine associations of depression and fatigue with discrepancies between subjective and objective cognitive functioning in pwMS. 177 participants with MS attending a University Hospital Department of Neurology MS Outpatient clinic completed the Brief International Cognitive Assessment for MS (BICAMS), MS Neuropsychological Questionnaire (MSNQ), Hospital Anxiety and Depression Scale (HADS) and Modified Fatigue Impact Scale (MFIS). To quantify the discrepancy between objective (BICAMS) and subjective (MSNQ) cognitive functioning, discrepancy scores were calculated by subtracting MSNQ z-score from composite BICAMS z-score. Based on their discrepancy score, participants were grouped as 'Underestimated', 'Overestimated' and 'Non-discrepant'. 39% of the total sample demonstrated poorer subjective cognitive functioning than their objective cognitive performance suggested ('Underestimated'). 23% of the total sample indicated lower objective scores than their subjective report suggests ('Overestimated'). 38% participants indicated relatively no discrepancy between objective and subjective cognitive measures ('Non-discrepant'). Significant differences were observed between the discrepancy groups in terms of depression and fatigue, with the 'Underestimated' group demonstrating greater levels of depression and fatigue (ps < .01). Regression analysis indicated that cognitive fatigue and depression significantly contributed to variance in subjective cognitive functioning. Our findings suggest that subjective reports of cognitive function may be influenced by depression and fatigue, emphasising the importance of cognitive, mood and fatigue screening as part of routine clinical care., (© 2022 The British Psychological Society.)

Background: Cognitive impairments are well-documented in multiple sclerosis (MS), while speech impairments are often overlooked despite their significant effect on quality of life. For effective clinical management of multisystem conditions such as MS, consideration should be given to the interaction between deficits in multiple domains, such as speech and cognition. To evaluate speech rate measures of spontaneous and read speech, in people with MS and to examine the link between speech and cognition., Methods: Forty-five people with MS and 25 controls underwent an extensive cognitive battery, including executive functioning, information processing and memory tasks, and completed two speech tasks: a reading task and a picture description task, from which speech rate measures were derived., Results: The progressive MS cohort had reduced articulation ( p  < 0.04) and speech rate ( p  < 0.02) compared to controls and those with relapsing MS. Regression models also revealed information processing speed accounted for 18% to 30% of the variance of spontaneous speech rate measures, and 27% of read speech. Executive functioning accounted for a further 10% of the variance of speech rate in those with MS., Conclusions: The present study suggests that speech production is contingent on cognitive ability, with information processing speed and executive functioning linked with speech timing patterns., Competing Interests: Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is a frequently seen burdensome adverse event of cancer therapy. The 5-HT3 receptor antagonist ondansetron has improved the rates of CINV but, unfortunately, up to 30% of patients do not obtain satisfactory control. This study examined whether genetic variations in a relevant drug-metabolizing enzyme (CYP2D6), transporter (ABCB1), or receptor (5-HT3) were associated with ondansetron failure., Methods: DNA was extracted from blood and used to genotype: ABCB1 (3435C > T (rs1045642) and G2677A/T (rs2032582)), 5-HT3RB (rs3758987 T > C and rs45460698 (delAAG/dupAAG)), and CYP2D6 variants. Ondansetron failure was determined by review of the medical records and by patient-reported outcomes (PROs)., Results: One hundred twenty-nine patients were approached; 103 consented. Participants were less than 1 to 33 years (mean 6.85). A total of 39.8% was female, 58.3% was White (22.3% Black, 19.4% other), and 24.3% was Hispanic. A majority had leukemia or lymphoma, and 41 (39.8%) met the definition of ondansetron failure. Of variants tested, rs45460698 independently showed a significant difference in risk of ondansetron failure between a mutant (any deletion) and normal allele (p = 0.0281, OR 2.67). Age and BMI were both predictive of ondansetron failure (age > 12 (OR 1.12, p = 0.0012) and higher BMI (OR 1.13, p = 0.0119)). In multivariate analysis, age > 12 was highly predictive of ondansetron failure (OR 7.108, p = 0.0008). rs45460698 was predictive when combined with an increased nausea phenotype variant of rs1045642 (OR 3.45, p = 0.0426)., Conclusion: Select phenotypes of 5-HT3RB and ABCB1, age, and potentially BMI can help predict increased risk for CINV in a diverse pediatric oncology population., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)