Goal setting as part of a holistic intervention to promote independence in older people with mild frailty: a process evaluation alongside a randomised controlled trial.

BACKGROUND: Frailty is a condition resulting from a decline in physiological reserves caused by an accumulation of several deficits, which progressively impairs the ability to recover from health adverse events. Following a promising feasibility study, the HomeHealth trial assessed a holistic tailored intervention for older adults with mild frailty to promote independence in their own homes, compared with usual care. We aimed to understand how goal setting worked among older people with mild frailty. METHODS: This study was a process evaluation alongside the HomeHealth randomised trial in older adults with mild frailty. The intervention was delivered at participants' homes, either in person or by telephone or videoconferencing. We carried out semi-structured interviews with older participants who had received the intervention (between three and six appointments), on average 233 days (range 68-465) after their last appointment, purposively sampled according to age, gender, number of sessions attended, adverse events, ethnicity, Index of Multiple Deprivation, Montreal Cognitive Assessment (MoCA) and Barthel scores, research site, and HomeHealth worker. We also conducted interviews with HomeHealth workers who delivered the intervention (n=7). Interviews explored the experience and process of goal setting, benefits and challenges, perceived progress, and behaviour change maintenance after the service had finished. Ethics approval was obtained, and all participants gave informed consent. Interviews were thematically analysed. HomeHealth workers kept formal records of goals set and assessed progress towards goals (0-2 rating scale) during six monthly-sessions, which were descriptively summarised. FINDINGS: 56 interviews were completed between July 15, 2022, and May 18, 2023. Study participants (n=49) had a mean age of 80 years (range 66-94), including 32 (65%) women and 17 (35%) men. Participants self-identified as White (n=42), Asian (n=3), Black (n=2), Mixed (n=1), and other ethnic (n=1) backgrounds. Findings suggested goal setting could be both a challenge and a motivator for older participants with mild frailty. Goal setting worked well when the older person could identify a clear need and set realistic goals linked to functioning, which led to a positive sense of achievement. Challenges occurred when older people were already accessing multiple resources and health services, or where the terminology of "goals" was off-putting due to work or school connotations. Average progress towards goals was 1·15/2. Most participants set goals around improving mobility (or a combination of mobility and another goal type such as socialising), and there was evidence of participants sustaining these behaviour changes after the intervention. INTERPRETATION: Older people with mild frailty can engage well with goal setting to promote independence. The lapse between receiving the intervention and being interviewed limited recall for some participants. However, the acceptability and adherence to the intervention for older people with mild frailty, and their moderate progress towards goals, should encourage further tailored and person-centred practices to promote their independence. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment.

What are we planning, exactly? The perspectives of people with intellectual disabilities, their carers and professionals on end-of-life care planning: A focus group study.

BACKGROUND: Deaths of people with intellectual disabilities are often unplanned for and poorly managed. Little is known about how to involve people with intellectual disabilities in end-of-life care planning. AIM: To explore the perspectives of people with intellectual disabilities, families, health and social care professionals and policy makers on end-of-life care planning within intellectual disability services. DESIGN: A total of 11 focus groups and 1 semi-structured interview were analysed using qualitative framework and matrix analysis. The analysis was conducted inclusively with co-researchers with intellectual disabilities. SETTING/PARTICIPANTS: A total of 60 participants (14 people with intellectual disabilities, 9 family carers, 21 intellectual disability professionals, 8 healthcare professionals and 8 policy makers) from the UK. RESULTS: There were differences in how end-of-life care planning was understood by stakeholder groups, covering four areas: funeral planning, illness planning, planning for living and talking about dying. This impacted when end-of-life care planning should happen and with whom. Participants agreed that end-of-life care planning was important, and most wanted to be involved, but in practice discussions were postponed. Barriers included issues with understanding, how or when to initiate the topic and a reluctance to talk about dying. CONCLUSIONS: To develop effective interventions and resources aiding end-of-life care planning with people with intellectual disabilities, clarity is needed around what is being planned for, with whom and when. Research and development are needed into supporting intellectual disability staff in end-of-life care planning conversations. Collaboration between intellectual disability staff and palliative care services may facilitate timely end-of-life care planning and thus optimal palliative end-of-life care.

Respect for the journey: a survivor-led investigation of undergoing psychotherapy assessment.

PURPOSE: Psychotherapy assessments are key decision points for both clients and services, carrying considerable weight on both sides. Limited research indicates that assessments have immediate and long-term impacts on clients, particularly where trauma has been experienced, affecting engagement with therapy. Understanding assessments from clients' perspectives can inform service development and improve client experience. METHODS: This is a survivor-led exploration of clients' experiences of undergoing assessment for talking therapies. Interviews were conducted with seven people who had undergone assessment for psychological therapies in third sector and NHS services. Interviews were recorded, transcribed and analysed thematically. RESULTS: The core theme was 'respect for the journey' reflecting the need expressed by participants for their life experiences prior to the assessment to be given full respect and consideration. Six sub-themes were identified: trauma and desperation, fear of judgement, search for trust and safety, sharing and withholding (a balancing act), feeling deconstructed, and finding hope. CONCLUSIONS: The findings highlight the heightened emotional power surrounding psychotherapy assessments, reflecting the journey participants had undertaken to reach this point. The dilemma facing clients at the heart of an assessment-how much to share and how much to withhold-demonstrates the importance for services and assessors of treating the journey a client has made to the assessment with care and respect. Findings indicate the value of services and practitioners undertaking a trauma-informed approach to assessment encounters.

What are the Challenges and Resilience Resources Identified by Informal Carers During the First UK COVID-19 Lockdown? A Longitudinal Qualitative Study Using Naturalistic Data.

COVID-19 has posed serious challenges for informal carers living in the UK. This article examines some of the specific challenges facing carers and the resources they used to manage them throughout the first UK lockdown. We used a framework approach to analyse naturalistic, longitudinal data from 30 carers taking part in 96 of Mobilise's daily Virtual Cuppas between March and July 2020. We found that lack of information and social restrictions cumulatively impacted carers' sense of certainty, control and motivation. This took an emotional toll on the carers, leading to exhaustion and burden. However, carers quickly established new routines and used humour and self-care to actively manage their wellbeing. Carers received support but also provided it to those in need, including fellow members of the caregiving community, supporting an ecological approach to carer resilience. Our findings may be used to anticipate challenges and promote protective resilience resources in future lockdowns.

Histopathologic, immunophenotypic, and mutational landscape of follicular lymphomas with plasmacytic differentiation.

Follicular lymphomas with plasmacytic differentiation (FL-PCD) include two major subtypes: one with predominantly interfollicular PCD that usually harbors a BCL2 rearrangement (BCL2-R), and a second that has predominantly intrafollicular PCD and the frequent absence of a BCL2-R. It is proposed that these latter cases share some features with marginal zone lymphomas (MZL). To further explore this hypothesis in an expanded cohort of FL-PCD, a clinicopathologic investigation of 25 such cases was undertaken including an analysis of their mutational landscape. The 10 interfollicular FL-PCDs exhibited typical intrafollicular centrocytes/centroblasts (90%), CD10 expression (90%), full PCD including expression of CD138 by the plasma cells (PC) (100%), and PCs with class-switched immunoglobulin heavy chains (70%). These cases were BCL2-R positive (100%), BCL6-R positive in 30%, lacked extra BCL2 copies, and only 22% had extra copies of BCL6. Similar to classic FLs, 80% of interfollicular FL-PCDs harbored mutations in epigenetic regulators KMT2D (70%), CREBBP (40%), and/or EZH2 (30%). In contrast, only 45% of 11 intrafollicular FL-PCDs demonstrated typical intrafollicular centrocytes/centroblasts, 55% were CD10(-), 80% contained IgM+ PCs, and only 27% harbored BCL2-Rs. BCL6-Rs were identified in 27% of intrafollicular FL-PCD, while 60% showed extra copies of BCL2 and 50% extra copies of BCL6, consistent with complete or partial trisomies of chromosomes 18 and 3, respectively. Only 54% of intrafollicular FL-PCDs showed mutations in epigenetic regulators. Both subtypes showed mutational differences compared to classic FL, but only the interfollicular subtype showed differences from what is reported for nodal MZL. Four additional cases showed mixed intra- and interfollicular PCD. These results suggest that FL-PCD has some distinctive features and supports the existence of two major subtypes. The interfollicular PCD subtype shares many features with classic FL. The intrafollicular FL-PCDs are more heterogeneous, have differences from classic FL, and have a greater morphologic, immunophenotypic, and genetic overlap with MZL.

Genomic landscape of Epstein-Barr virus-positive extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue.

Epstein-Barr virus (EBV)-positive extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas) were initially described in solid organ transplant recipients, and, more recently, in other immunodeficiency settings. The overall prevalence of EBV-positive MALT lymphomas has not been established, and little is known with respect to their genomic characteristics. Eight EBV-positive MALT lymphomas were identified, including 1 case found after screening a series of 88 consecutive MALT lymphomas with EBER in situ hybridization (1%). The genomic landscape was assessed in 7 of the 8 cases with a targeted high throughput sequencing panel and array comparative genomic hybridization. Results were compared to published data for MALT lymphomas. Of the 8 cases, 6 occurred post-transplant, 1 in the setting of primary immunodeficiency, and 1 case was age-related. Single pathogenic/likely pathogenic mutations were identified in 4 of 7 cases, including mutations in IRF8, BRAF, TNFAIP3, and SMARCA4. Other than TNFAIP3, these genes are mutated in <3% of EBV-negative MALT lymphomas. Copy number abnormalities were identified in 6 of 7 cases with a median of 6 gains and 2 losses per case, including 4 cases with gains in regions encompassing several IRF family or interacting genes (IRF2BP2, IRF2, and IRF4). There was no evidence of trisomies of chromosomes 3 or 18. In summary, EBV-positive MALT lymphomas are rare and, like other MALT lymphomas, are usually genetically non-complex. Conversely, while EBV-negative MALT lymphomas typically show mutational abnormalities in the NF-κB pathway, other than the 1 TNFAIP3-mutated case, no other NF-κB pathway mutations were identified in the EBV-positive cases. EBV-positive MALT lymphomas often have either mutations or copy number abnormalities in IRF family or interacting genes, suggesting that this pathway may play a role in these lymphomas.

The impact of working as a peer worker in mental health services: a longitudinal mixed methods study.

BACKGROUND: Peer workers are increasingly employed in mental health services to use their own experiences of mental distress in supporting others with similar experiences. While evidence is emerging of the benefits of peer support for people using services, the impact on peer workers is less clear. There is a lack of research that takes a longitudinal approach to exploring impact on both employment outcomes for peer workers, and their experiences of working in the peer worker role. METHODS: In a longitudinal mixed methods study, 32 peer workers providing peer support for discharge from inpatient to community mental health care - as part of a randomised controlled trial - undertook in-depth qualitative interviews conducted by service user researchers, and completed measures of wellbeing, burnout, job satisfaction and multi-disciplinary team working after completing training, and four and 12 months into the role. Questionnaire data were summarised and compared to outcomes for relevant population norms, and changes in outcomes were analysed using paired t-tests. Thematic analysis and interpretive workshops involving service user researchers were used to analysis interview transcripts. A critical interpretive synthesis approach was used to synthesise analyses of both datasets. RESULTS: For the duration of the study, all questionnaire outcomes were comparable with population norms for health professionals or for the general population. There were small-to-medium decreases in wellbeing and aspects of job satisfaction, and increase in burnout after 4 months, but these changes were largely not maintained at 12 months. Peer workers felt valued, empowered and connected in the role, but could find it challenging to adjust to the demands of the job after initial optimism. Supervision and being part of a standalone peer worker team was supportive, although communication with clinical teams could be improved. CONCLUSIONS: Peer workers seem no more likely to experience negative impacts of working than other healthcare professionals but should be well supported as they settle into post, provided with in-work training and support around job insecurity. Research is needed to optimise working arrangements for peer workers alongside clinical teams.

Evaluation of outflow temperatures generated by a dry heat fluid warmer at low fluid rates.

OBJECTIVE: To evaluate the output temperature of a dry heat fluid warmer at fluid rates typically used in small animal veterinary patients. STUDY DESIGN: Prospective in vitro study. ANIMALS: None. METHODS: Ambient temperature lactated Ringer's (17.9-18.8 °C) was delivered via a dry heat fluid warmer. A temperature probe was used to measure fluid outflow temperature from the compatible giving set at 5, 10, 20, 50, 70, 80, 100, 200, 300, 400 and 500 mL hour-1. Outflow fluid temperature at plateau (two consecutive readings within 0.1 °C) was compared with baseline fluid temperature (fluid warmer turned off) to calculate temperature changes at each rate. Kruskal-Wallis test was used to compare changes in temperature and time to plateau temperature. Dunn's post hoc test was used to test for significant differences in temperature compared to 5 mL hour-1; p value < 0.05. RESULTS: Median plateau outflow temperature increased as fluid rate increased, with temperatures of 18.5, 18.6, 18.7, 18.8, 19.4, 19.4, 21.5, 25.3, 28.5, 30.7 and 32.6 °C, at flow rates of 5, 10, 20, 50, 70, 80, 100, 200, 300, 400 and 500 mL hour-1. Fluid rates > 100 mL hour-1 showed significant increases from baseline (p = 0.021) There was no difference in temperature change from baseline at fluid rates < 100 mL hour-1 (p > 0.05). Compared to plateau temperature at 5 mL hour-1, there was a statistical difference in plateau temperature above 100 mL hour-1(p = 0.0207). Maximum outflow plateau temperature was 32.6 °C at 500 mL hour-1. CONCLUSIONS AND CLINICAL RELEVANCE: A dry heat fluid warmer has significantly decreased efficacy at low fluid rates, with no statistically significant increase in fluid temperature at fluid rates below 100 mL hour-1 at the end of a compatible fluid line. Inline dry heat fluid warmers are ineffective at fluid rates below 100 mL hour-1.

UKCGG Consensus Group guidelines for the management of patients with constitutional TP53 pathogenic variants.

Constitutional pathogenic variants in TP53 are associated with Li-Fraumeni syndrome or the more recently described heritable TP53-related cancer syndrome and are associated with increased lifetime risks of a wide spectrum of cancers. Due to the broad tumour spectrum, surveillance for this patient group has been limited. To date, the only recommendation in the UK has been for annual breast MRI in women; however, more recently, a more intensive surveillance protocol including whole-body MRI (WB-MRI) has been recommended by International Expert Groups. To address the gap in surveillance for this patient group in the UK, the UK Cancer Genetics Group facilitated a 1-day consensus meeting to discuss a protocol for the UK. Using a preworkshop survey followed by structured discussion on the day, we achieved consensus for a UK surveillance protocol for TP53 carriers to be adopted by UK Clinical Genetics services. The key recommendations are for annual WB-MRI and dedicated brain MRI from birth, annual breast MRI from 20 years in women and three-four monthly abdominal ultrasound in children along with review in a dedicated clinic.

High prevalence of allergy in patients undergoing in vitro fertilization and embryo transfer.

PURPOSE: To determine the prevalence of allergy in couples undergoing in vitro fertilization (IVF) and the relationship between having allergy and IVF treatment outcomes. DESIGN: A retrospective cohort study of female infertility patients aged 20-49 years and their male partners undergoing IVF cycles from August 2010 to December 2016 in an academic fertility program. RESULTS: Prevalence data was collected for 493 couples (935 cycles). Over half of the female patients (54%) had at least one reported allergy versus the cited US prevalence of 10-30%. Antibiotic (54.7%) and non-antibiotic medication (39.2%) were the most common female allergy subtypes. Fewer male patients reported allergy (21.7%). Data on ß-hCG outcomes were calculated for 841 cycles from 458 couples with no significant relationship found except for number of cycles including ICSI and number of embryos transferred per cycle (1.81 for those without allergy vs 2.07 for those with allergy, p = 0.07). Female patients with allergy were marginally statistically more likely to have a negative ß-hCG (p = 0.07) and less likely to have a successful cycle (p = 0.06). When allergy subgroups were evaluated, there were no significant differences between groups except for a higher number of embryos transferred in women with environmental/other allergies (p = 0.02). CONCLUSION: The prevalence of allergy among patients seeking infertility treatment is high compared with the general population. However, allergy was not found to be associated with IVF cycle outcomes. These findings are likely primarily limited by difficulty in defining specific allergy types within a retrospective study.

Impact of preanaesthetic echocardiography on the planned anaesthetic management of cats.

OBJECTIVE: To assess the impact of preanaesthetic echocardiography on the subsequent intended anaesthetic management plan in cats with incidental clinical findings that may indicate cardiac disease. STUDY DESIGN: Clinical study involving cats undergoing echocardiography and subsequent anaesthesia. ANIMALS: A total of 40 client-owned cats. METHODS: Echocardiography was performed in conscious cats and the information was used to plan anaesthesia or sedation. An information sheet including relevant history, temperament, body condition score, clinical examination findings, current medication and results of any relevant tests such as haematology, biochemistry or Doppler blood pressure measurement was sent to three specialist anaesthetists and virtual case management plans were designed for each cat in two steps: step 1) anaesthetists were unaware of echocardiography results; and step 2) anaesthetists were aware of echocardiography results. In the second step the anaesthetists documented any changes to their original management plan, as either 'step-up' or 'step-down'. RESULTS: Of the 40 cats, 26 had murmurs, four had a gallop rhythm, four had both findings and six had other findings. Pathology of potential haemodynamic significance was found on echocardiography in 23 cats, 17 of which anaesthetists had correctly identified as having disease before echocardiography. A proportion of cats with murmurs were subsequently deemed to have no significant pathology after echocardiography. Echocardiography findings in these cases were: dynamic left ventricular outflow tract obstruction (DLVOTO) without hypertrophy; DLVOTO without hypertrophy + dynamic right ventricular outflow tract obstruction (DRVOTO); DRVOTO; valvular dysplasia; normal. In a median of 26/40 (range 16-38) of cases, the anaesthetic plan was changed after provision of further information; in 15/40 (8-20) cases, this was a 'step-up' in care and in eight/40 (6-23) it was a 'step-down' in care. In cases with atrial enlargement (left atrium to aortic ratio of >1.6) and deemed at risk of cardiac failure, alpha-2 agonist use changed considerably with availability of echocardiography findings. CONCLUSION: and clinical relevance Where there are abnormal cardiac findings on clinical examination in cats, echocardiography is required to accurately assess anaesthetic risk . The availability of echocardiographic information positively influences anaesthetic management.

Knowledge and expertise in care practices: the role of the peer worker in mental health teams.

Our research examines how different forms of knowledge and expertise are increasingly important in caring for people experiencing mental illness. We build on theoretical developments regarding multiple ontologies of knowing about illness. We examine how experiential knowledge of mental health problems, learned by being subject to illness rather than through objective study, is enacted in mental healthcare teams. We focus on Peer Workers (PW), individuals who have lived experience of mental health problems, and who contribute knowledge and expertise to mental health care within multidisciplinary healthcare teams. Our longitudinal study was undertaken over 2 years by a multidisciplinary team who conducted 91 interviews with PW and other stakeholders to peer support within a comparative case study design. We show how workers with tacit, experiential knowledge of mental ill health engaged in care practice. First, we show how subjective knowing is underpinned by unique socialisation that enables the development of shared interactional spaces. Second, we point to how the situated nature of subjective knowing is uniquely embedded in time and space and allows for the alignment of embodied knowledge with trajectories of care. Third, we provide insight into how subjective forms of expertise might be incorporated into multidisciplinary care.

Hematolymphoid neoplasms are common in bone marrow biopsies performed for non-specific, diffuse marrow signal alterations on magnetic resonance imaging.

AIMS: MRI is an imaging modality used for a wide range of clinical indications. Occasionally, non-specific, diffuse T1 marrow signal alterations are identified, which may prompt a bone marrow biopsy (BM). However, there is little data on the clinicopathologic significance of this signal alteration. This study evaluated the frequency and nature of pathologic findings in BM performed to evaluate diffuse MRI T1 marrow signal alterations. METHODS: Records from January 2003 to May 2015 were searched for BM performed to evaluate abnormal MRIs. 179 cases were identified. Patients with nodular/destructive bone lesions on MRI or other imaging studies, or a previous diagnosed metastatic tumor or hematologic malignancy were excluded, resulting in 45 cases. RESULTS: The patients included 22 males and 23 females with a median age of 56 years. The location of the MRI T1 marrow signal alterations included spine, pelvis, knee, skull, femur, and arm. 19/45 patients had neoplasms identified in the BM. The remaining 26 patients had benign BM findings. There was a significant difference in hemoglobin values in patients with neoplastic versus benign BM findings (p = 0.037, unpaired Student's t-test). CONCLUSIONS: Diffuse T1 marrow signal alterations on MRI should warrant a BM evaluation, as 42% of cases showed an underlying hematolymphoid neoplasm or metastatic tumor, even when patients with a known history of malignancy were excluded. When faced with a BM from a patient with a non-specific, diffuse MRI signal alteration, a pathologist should have a high index of suspicion for a malignant neoplasm, most often of hematopoietic/lymphoid type.

Computed tomographic arthrography is a useful adjunct to survey computed tomography and arthroscopic evaluation of the canine shoulder joint.

The aim of this retrospective, methods comparison study was to assess the diagnostic utility of computed tomographic arthrography in the assessment of various intraarticular shoulder pathologies in dogs in comparison with survey computed tomography (CT), using arthroscopic examination as the reference standard. Computed tomography, computed tomographic arthrography, and arthroscopic findings of 46 scapulohumeral joints of dogs with forelimb lameness were reviewed retrospectively. Predefined sites were assessed for the presence or absence of disease. If a lesion was present, a prespecified pathology was designated. Computed tomographic arthrography was found to be a safe technique which provided a superior diagnostic efficacy relative to survey CT for the assessment of the biceps tendon and biceps tendon sheath (sensitivity 71%, specificity 75%, positive likelihood ratio 2.9, negative likelihood ratio 0.38) and humeral head cartilage (sensitivity 65%, specificity 97%, positive likelihood ratio 19, negative likelihood ratio 0.37). Computed tomography and computed tomographic arthrography provided additional diagnostic information to arthroscopy in regard to osteophytosis, subchondral defects, and joint mice. Computed tomographic arthrography alone was of limited diagnostic value for assessment of the medial and lateral glenohumeral ligaments (sensitivity 13% and 0%, specificity 1% and 78%, positive likelihood ratios unmeasurable and 0, negative likelihood ratios 0.88 and 1.29, respectively) and the subscapularis tendon (sensitivity 14%, specificity 98%, positive likelihood ratio 5.7, negative likelihood ratio 0.88). Computed tomographic arthrography is therefore a useful adjunct to survey CT and arthroscopic evaluation of the canine shoulder joint, however, is not a replacement for these techniques.

'Unfit for human consumption': a study of the contamination of formula milk fed to young children in East Java, Indonesia.

OBJECTIVES: To examine levels of bacterial contamination in formula feeding bottles in Sidoarjo, East Java, and to assess the preparation practices that may have been responsible. METHODS: A cross-sectional study was conducted among 92 randomly selected households with children under the age of two who were bottle-fed formula. In each household, we carried out video observation of mothers/caregivers preparing bottles, and examined samples of formula for coliform bacteria and Escherichia coli (E. coli). In-depth interviews were conducted with a subsample of 20 mothers. RESULTS: A total of 88% of the formula feeds were contaminated with total coliforms at a level >10 MPN/ml, and 45% contained E. coli. These feeds were defined as 'unfit for human consumption'. In the video observations, none of the mothers complied with all five WHO-recommended measures of hygienic formula feed preparation. Only two mothers washed their hands with soap prior to formula preparation. Most mothers also failed to clean or sterilise the bottle and clean the preparation area. In-depth interviews confirmed that such suboptimal hygiene practices were common. CONCLUSION: The high levels of contamination found highlight that bottles are an important faecal-oral exposure pathway resulting from poor hygiene practices during bottle preparation.

ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes.

Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALK-positive ALCL but lacks chromosomal rearrangements of the ALK gene. The genetic and clinical heterogeneity of ALK-negative ALCL has not been delineated. We performed immunohistochemistry and fluorescence in situ hybridization on 73 ALK-negative ALCLs and 32 ALK-positive ALCLs and evaluated the associations among pathology, genetics, and clinical outcome. Chromosomal rearrangements of DUSP22 and TP63 were identified in 30% and 8% of ALK-negative ALCLs, respectively. These rearrangements were mutually exclusive and were absent in ALK-positive ALCLs. Five-year overall survival rates were 85% for ALK-positive ALCLs, 90% for DUSP22-rearranged ALCLs, 17% for TP63-rearranged ALCLs, and 42% for cases lacking all 3 genetic markers (P < .0001). Hazard ratios for death in these 4 groups after adjusting for International Prognostic Index and age were 1.0 (reference group), 0.58, 8.63, and 4.16, respectively (P = 7.10 × 10(-5)). These results were similar when restricted to patients receiving anthracycline-based chemotherapy, as well as to patients not receiving stem cell transplantation. Thus, ALK-negative ALCL is a genetically heterogeneous disease with widely disparate outcomes following standard therapy. DUSP22 and TP63 rearrangements may serve as predictive biomarkers to help guide patient management.

Three cases of thyroid cancer following the diagnosis of testicular cancer: treatment-related complication or genetics?

Large-scale epidemiological studies have shown that the incidence of second primary thyroid cancer in subjects diagnosed and treated for testicular cancer is raised. This finding is strongly associated to treatment with radiotherapy and/or chemotherapy and it is explained by their mutagenic effect. On the other hand, inherited cancer susceptibility syndromes inducing both testicular and thyroid cancers denote that these tumours might share common genomic aberrations. We herein present our experience with three cases of metachronous development of thyroid cancer after diagnosis and treatment of testicular cancer in our tertiary cancer centre. Our case report contributes to the limited available literature on such findings and aims to raise awareness of the cancer physicians treating these particular tumour types.

Evidence of a specialized feeding niche in a Late Triassic ray-finned fish: evolution of multidenticulate teeth and benthic scraping in †Hemicalypterus.

Fishes have evolved to exploit multiple ecological niches. Extant fishes in both marine (e.g., rabbitfishes, surgeonfishes) and freshwater systems (e.g., haplochromine cichlids, characiforms) have evolved specialized, scoop-like, multidenticulate teeth for benthic scraping, feeding primarily on algae. Here, I report evidence of the oldest example of specialized multidenticulate dentition in a ray-finned fish, †Hemicalypterus weiri, from the Upper Triassic Chinle Formation of southeastern Utah (∼210-205 Ma), USA. †H. weiri is a lower actinopterygian species that is phylogenetically remote from modern fishes, and has evolved specialized teeth that converge with those of several living teleost fishes (e.g., characiforms, cichlids, acanthurids, siganids), with a likely function of these teeth being to scrape algae off a rock substrate. This finding contradicts previously held notions that fishes with multicuspid, scoop-like dentition were restricted to teleosts, and indicates that ray-finned fishes were diversifying into different trophic niches and exploring different modes of feeding earlier in their history than previously thought, fundamentally altering our perceptions of the ecological roles of fishes during the Mesozoic.

Preparation of 3-benzyloxy-2-pyridinone functional linkers: Tools for the synthesis of 3,2-hydroxypyridinone (HOPO) and HOPO/hydroxamic acid chelators.

In contrast to 2,3-dihydroxypyridine, the 3-benzyloxy protected derivative, 2, undergoes facile alkylation at ambient temperatures with a variety of functionalized alkyl halides in good yields. This alkylation has been used to prepare a number of linkers that permit the attachment of 3,2-HOPO moieties onto various scaffolds using a wide range of coupling methods. The Mitsunobu reaction of 2 with representative alcohols was found to be of limited value due to competing O-alkylation that led to product mixtures. The phthalimide 3j can be converted in two steps to HOPO isocyanate 6 in excellent yields. Isocyanate 6 can be coupled to amines at room temperature or to alcohols in refluxing dichloroethane to obtain the corresponding urea or carbamate linked ligand systems. The coupling of isocyanate 6 with TREN followed by deprotection gave the tris-HOPO 10, an interesting target as it has both cationic and anionic binding sites. The HOPO hydroxylamine linker 11 was shown to be especially valuable as its coupling with carboxylic acids proceeds with the concomitant generation of an additional hydroxamate ligand moiety in the framework. The utility of this linker was shown by the preparation of two mixed HOPO-hydroxamate chelators, 16 and 19, based on the structure of desferrioxamine, a well-known trihydroxamate siderophore.