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Decades of theoretical and empirical work have suggested the hippocampus instantiates some form of a cognitive map. Yet, tests of competing theories have been limited in scope and largely qualitative in nature. Here, we develop a novel framework to benchmark model predictions against observed neuronal population dynamics as animals navigate a series of geometrically distinct environments. In this task space, we show a representational structure in the dynamics of hippocampal remapping that generalizes across brains, discriminates between competing theoretical models, and effectively constrains biologically viable model parameters. With this approach, we find that accurate models capture the correspondence in spatial coding of a changing environment. The present dataset and framework thus serve to empirically evaluate and advance theories of cognitive mapping in the brain., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Evidence from neurophysiological and genetic studies demonstrates that activity sparsity-the proportion of neurons that are active at a given time in a population-systematically varies across the canonical trisynaptic circuit of the hippocampus. Recent work has also shown that sparsity varies across the hippocampal dorsoventral (long) axis, wherein activity is sparser in ventral than dorsal regions. While the hippocampus has a critical role in long-term memory (LTM), whether sparsity across the trisynaptic circuit and hippocampal long axis is task-dependent or invariant remains unknown. Importantly, representational sparsity has significant implications for neural computation and theoretical models of learning and memory within and beyond the hippocampus. Here we used functional molecular imaging to quantify sparsity in the rat hippocampus during performance of the Morris water task (MWT) and contextual fear discrimination (CFD) - two popular and distinct assays of LTM. We found that activity sparsity is highly reliable across memory tasks, wherein activity increases sequentially across the trisynaptic circuit (DG < CA3 < CA1) and decreases across the long axis (ventral

Background: Intraoperative Continuous Renal Replacement Therapy (iCRRT) can prevent life-threatening complications, facilitate fluid management, and maintain metabolic homeostasis during liver transplantation (LT) in adults. There is a paucity of data in pediatric LT. We evaluated the safety, efficacy, and impact on survival of iCRRT in pediatric LT., Methods: We conducted a retrospective cohort study of all children requiring CRRT pre-OLT at a quaternary children's hospital from 2014 to 2022. Demographic characteristics, intraoperative events, and post-LT outcomes were compared between those who received iCRRT and those who did not., Results: Out of 306 patients who received LT, 30 (10%) were supported with CRRT at least 24 h prior to LT, of which 11 (36%) received iCRRT. The two cohorts were similar in demographics, diagnosis of liver disease, and severity of illness. The iCRRT patients experienced massive blood loss and increased transfusion requirements. There was no difference in intraoperative metabolic balance. One-year post-LT mortality rates were similar., Conclusion: ICRRT is safe in critically ill children with pre-LT renal dysfunction. It optimizes fluid and blood product resuscitation while maintaining metabolic homeostasis. Candidates need to be carefully chosen for this highly resource-intensive therapy to benefit this fragile population., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Metastasis involves epithelial-to-mesenchymal transition (EMT), a process that is regulated by complex gene networks, where their deliberate disruption may yield a promising outcome. However, little is known about mechanisms that coordinate these metastasis-associated networks. To address this gap, hub genes with broad engagement across various human cancers by analyzing the transcriptomes of different cancer cell types undergoing EMT are identified. The oncogenic signaling adaptor protein tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) is ranked top for its clinical relevance and impact. The cellular kinome and transcriptome data are surveyed to construct the regulome of YWHAG, revealing stress responses and metabolic processes during cancer EMT. It is demonstrated that a YWHAG-dependent cytoprotective mechanism in the regulome is embedded in EMT-associated networks to protect cancer cells from oxidative catastrophe through enhanced autophagy during EMT. YWHAG deficiency results in a rapid accumulation of reactive oxygen species (ROS), delayed EMT, and cell death. Tumor allografts show that metastasis potential and overall survival time are correlated with the YWHAG expression level of cancer cell lines. Metastasized tumors have higher expression of YWHAG and autophagy-related genes than primary tumors. Silencing YWHAG diminishes primary tumor volumes, prevents metastasis, and prolongs the median survival period of the mice., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Cancer-related fatigue (CRF) is a common side effect and remains under-diagnosed. Screening of CRF by physical therapists (PTs) and patient perspectives of their experiences has not been comprehensively examined., Purpose: To survey PTs to understand the frequency of CRF screening, and to assess the knowledge and experiences of survivors as it relates to CRF., Methods: Two separate electronic surveys developed by the authors were distributed. One targeted oncology PTs, the other for adult survivors of cancer., Results: Of the 199 PT respondents, 36% reported screening for CRF at every encounter. Screening included interviews (46%) and/or standardized questionnaires (37%). The most common barriers to receiving treatment for CRF was lack of physician referrals and time constraints. Of patient responses (n = 61), 84% reported CRF as an important ongoing issue; 77% reported that they initiated the discussion about CRF with their provider, and 23% reported being told there were treatment options for CRF., Conclusion: CRF is common among cancer survivors. However, consistent screening by PTs is lacking. Patients with CRF frequently initiated the conversation with their providers because of symptoms and many patients were not told of treatment options. These findings represent a substantial gap in clinical practice regarding CRF screening and management.

In this issue of Neuron, Khatib et al. 1 and Geva et al. 2 present complementary and breakthrough discoveries demonstrating that elapsed time and active experience independently affect unique aspects of representational drift in the hippocampus., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cancer-related fatigue (CRF) is the most common side effect of cancer treatment. Regular surveillance is recommended, but few clinical practice guidelines transparently assess study bias, quality, and clinical utility in deriving recommendations of screening and assessment methods. The purpose of this clinical practice guideline (CPG) is to provide recommendations for the screening and assessment of CRF for health care professions treating individuals with cancer. Following best practices for development of a CPG using the Appraisal of Guidelines for Research and Evaluation (AGREE) Statement and Emergency Care Research Institute (ECRI) Guidelines Trust Scorecard, this CPG included a systematic search of the literature, quality assessment of included evidence, and stakeholder input from diverse health care fields to derive the final CPG. Ten screening and 15 assessment tools supported by 114 articles were reviewed. One screen (European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 Core Questionnaire) and 3 assessments (Piper Fatigue Scale-Revised, Functional Assessment of Chronic Illness Therapy-Fatigue, and Patient Reported Outcome Measurement Information System [PROMIS] Fatigue-SF) received an A recommendation ("should be used in clinical practice"), and 1 screen and 5 assessments received a B recommendation ("may be used in clinical practice"). Health care providers have choice in determining appropriate screening and assessment tools to be used across the survivorship care continuum. The large number of tools available to screen for or assess CRF may result in a lack of comprehensive research evidence, leaving gaps in the body of evidence for measurement tools. More research into the responsiveness of these tools is needed in order to adopt their use as outcome measures., Impact: Health care providers should screen for and assess CRF using one of the tools recommended by this CPG., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association.)

Evidence from genetic, behavioural, anatomical, and physiological study suggests that the hippocampus functionally differs across its longitudinal (dorsoventral or septotemporal) axis. Although, how to best characterize functional and representational differences in the hippocampus across its long axis remains unclear. While some suggest that the hippocampus can be divided into dorsal and ventral subregions that support distinct cognitive functions, others posit that these regions vary in their granularity of representation, wherein spatial-temporal resolution decreases in the ventral (temporal) direction. Importantly, the cognitive and granular hypotheses also make distinct predictions on cellular recruitment dynamics under conditions when animals perform tasks with qualitatively different cognitive-behavioural demands. One interpretation of the cognitive function account implies that dorsal and ventral cellular recruitment differs depending on relevant behavioural demands, while the granularity account suggests similar recruitment dynamics regardless of the nature of the task performed. Here, we quantified cellular recruitment with the immediate early gene (IEG) Arc across the entire longitudinal CA1 axis in female and male rats performing spatial- and fear-guided memory tasks. Our results show that recruitment is greater in dorsal than ventral CA1 regardless of task or sex, and thus support a granular view of hippocampal function across the long axis. We further discuss how future experiments might determine the relative contributions of cognitive function and granularity of representation to neuronal activity dynamics in hippocampal circuits., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy of negative pressure massage treatment (NPMT) compared with manual lymphatic drainage (MLD) in women with chronic breast cancer-related lymphedema (LE). We hypothesized that NPMT would result in greater improvements in LE and upper limb function., Design: Pilot single-blinded randomized controlled trial., Setting: Health sciences university., Participants: Of 64 women screened, 28 met eligibility requirements (ie, >18y of age; completed active treatment for breast cancer; had unilateral arm LE for ≥1y; were not receiving LE care; had stable LE) and were randomized to the NPMT (n=15) and control groups (n=13)., Interventions: The intervention group received NPMT and the control group received MLD; both received twelve 60-minute sessions over 4-6 weeks., Main Outcome Measures: Bioimpedance (lymphedema index [L-Dex] units]), limb volume (mL) calculated from limb circumference, and Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) score., Results: Outcomes were analyzed for 28 women. Compared to the MLD group, the NPMT group demonstrated greater improvement with a large effect size in L-Dex scores (P=.001; standardized mean difference [SMD]=-1.15; 95% confidence interval, -1.96 to -0.35) and interlimb volume differences (P=.038; SMD=-0.83; 95% confidence interval, -1.60 to -0.05). Differences in DASH scores were not statistically significant (P=.067)., Conclusions: Compared to MLD, treatment with NPMT resulted in greater improvement in L-Dex scores and interlimb volume differences in women with a duration of unilateral upper limb LE of >1 year. Our findings need to be confirmed in a larger randomized controlled trial., (Copyright © 2021 The American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to understand the barriers experienced by physicians when prescribing for older adults with multimorbidity in specialist outpatient clinics in Singapore., Methods: A modified Delphi study was conducted via email with 20 panel experts in the field of geriatric medicine. Barriers identified from an earlier scoping review were presented as statements to the panel., Results: Eleven barrier statements reached consensus with high importance according to the Delphi panel. Of these statements, seven (64%) belong to the domain of Environmental context and resources in the Theoretical Domains Framework (TDF), while the remaining barriers belong to the domains of skills, knowledge, intentions, and professional/social role and identity . The barriers are further linked to intervention functions in the Behaviour Change Wheel (BCW)., Conclusion: Linking the TDF domains to intervention functions revealed strategic directions for the development of an intervention to address the barriers and optimize prescribing., Competing Interests: We have no conflict of interest to declare., (© 2021 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Objective: Polypharmacy occurs in approximately 30% of older adults aged 65 years or more, particularly among those with multimorbidity. With polypharmacy, there is an associated risk of potentially inappropriate prescribing (PIP). The aims of this scoping review were to (1) identify the intervention elements that have been adopted to reduce PIP in the outpatient setting and (2) determine the behaviour change wheel (BCW) intervention functions performed by each of the identified intervention elements., Design: Scoping review DATA SOURCES: PubMed, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Web of Science and Cochrane Library databases, grey literature sources, six key geriatrics journals and the reference lists of review papers., Study Selection: All studies reporting an intervention or strategy that addressed PIP in the older adult population (age ≥65) with multimorbidity in the outpatient setting and in which the primary prescriber is the physician., Data Extraction: Data extracted from the included studies can be broadly categorised into (1) publication details, (2) intervention details and (3) results. This was followed by data synthesis and analysis based on the BCW framework., Results: Of 8195 studies yielded, 80 studies were included in the final analysis and 14 intervention elements were identified. An average of two to three elements were adopted in each intervention. The three most frequently adopted intervention elements were medication review (70%), training (26.3%) and tool/instrument(s) (22.5%). Among medication reviews, 70% involved pharmacists. The 14 intervention elements were mapped onto five intervention functions: 'education', 'persuasion', 'training', 'environmental restructuring' and 'enablement'., Conclusion: PIP is a multifaceted problem that involves multiple stakeholders. As such, interventions that address PIP require multiple elements to target the behaviour of the various stakeholders. The intervention elements and their corresponding functions identified in this scoping review will serve to inform the design of complex interventions that aim to reduce PIP., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Multiple trace theory (Nadel & Moscovitch, Current Opinion in Neurobiology, 1997, 7, 217-227) has proven to be one of the most novel and influential recent memory theories, and played an essential role in shifting perspective on systems-level memory consolidation. Here, we briefly review its impact and testable predictions and focus our discussion primarily on nonhuman animal experiments. Perhaps, the most often supported claim is that episodic memory tasks should exhibit comparable severity of retrograde amnesia (RA) for recent and remote memories after extensive damage to the hippocampus (HPC). By contrast, there appears to be little or no experimental support for other core predictions, such as temporally limited RA after extensive HPC damage in semantic memory tasks, temporally limited RA for episodic memories after partial HPC damage, or the existence of storage of multiple HPC traces with repeated reactivations. Despite these shortcomings, it continues to be a highly cited HPC memory theory., (© 2019 Wiley Periodicals, Inc.)

Pandemics are a significant stress test for a country's economic, political and health systems. An effective pandemic response demands a multi-pronged and multi-layered approach, comprising surveillance, containment, border control, as well as various social and community measures. In the wake of the novel coronavirus disease 2019 (COVID-19) pandemic, which has now infected more than 7 million people worldwide, strict quarantine measures are a commonplace, and a third of the world's population have now gone into some form of lockdown. With the exception of border control, all these response measures involve the contributions of family physicians and general practitioners (GPs) in one way or another. Primary care physicians form and lead the primary care network, which in turn forms the backbone of any healthcare system. Being the first point of contact for a significant proportion of patients, primary care physicians play an essential strategic function in the fight against disease, both during peacetime and in the event of a public health crisis. In this commentary, we examine and propose some of the key roles that they play in a pandemic, drawing examples from the current COVID-19 pandemic and past experiences. COVID-19 has showed us that the world is grossly unprepared for a pandemic, both in terms of our global management and the structure of our current primary health care systems, and this should provide the impetus for us to improve.

Previous work has shown that the dorsal hippocampus has greater activity than ventral regions during place navigation. Exposure to a novel context has also been found to increase hippocampal activation, possibly due to increased spatial demands. However, activation patterns in dorsal and ventral regions have not been investigated in the Morris water task (MWT), which remains the most popular assay of place memory in rodents. We measured activity in a large population of neurons across the CA1 dorsal-ventral axis by estimating nuclear Arc mRNA with stereologic systematic-random sampling procedures following changes to goal location or spatial context in the MWT in rats. Following changes to goal location or spatial context in the MWT, we did not find an effect on Arc mRNA expression in CA1. However, Arc expression was greater in the dorsal compared to the ventral aspect of CA1 during task performance. Several views might account for these observed differences in dorsal-ventral Arc mRNA expression, including task parameters or the granularity of representation that differs along the dorsal-ventral hippocampal axis. Future work should determine the effects of task differences and required memory precision in relation to dorsal-ventral hippocampal neuronal activity., (© 2019 Wiley Periodicals, Inc.)

Explanations of memory-guided navigation in rodents typically suggest that cue- and place-based navigations are independent aspects of behavior and neurobiology. The results of many experiments show that hippocampal damage causes both anterograde and retrograde amnesia (AA; RA) for place memory, but only RA for cue memory. In the present experiments, we used a concurrent cue-place water task (CWT) to study the effects of hippocampal damage before or after training on cue- and place-guided navigation, and how cue and place memory interact in damaged and control rats. We found that damaging the hippocampus before training caused a delay in the expression of cue-place navigation strategies relative to intact control animals; surprisingly, place navigation strategies emerged following pre-training hippocampal damage. With additional training, both control and damaged rats used local cues to navigate in the CWT. Damaged animals also show minor impairments in latency to navigate to the correct cue following a cue contingency reversal. By contrast to these anterograde effects, damage made after training causes RA for cue choice accuracy and latency to navigate to the correct cue. In addition, the extent of hippocampal damage predicted impairments in choice accuracy when lesions were made after training. These data extend previous work on the role of the hippocampus in cue and place memory-guided navigation, and show that the hippocampus plays an important role in both aspects of memory and navigation when present during the learning experience., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

The ventral hippocampus (vHPC) has been implicated in learning and memory functions that seem to differ from its dorsal counterpart. The goal of this series of experiments was to provide further insight into the functional contributions of the vHPC. Our previous work implicated the vHPC in spatial learning, inhibitory learning, and fear conditioning to context. However, the specific role of vHPC on these different forms of learning are not clear. Accordingly, we assessed the effects of neurotoxic lesions of the ventral hippocampus on retention of a conditioned inhibitory association, early versus late spatial navigation in the water task, and discriminative fear conditioning to context under high ambiguity conditions. The results showed that the vHPC was necessary for the expression of conditioned inhibition, early spatial learning, and discriminative fear conditioning to context when the paired and unpaired contexts have high cue overlap. We argue that this pattern of effects, combined with previous work, suggests a key role for vHPC in the utilization of broad contextual representations for inhibition and discriminative memory in high ambiguity conditions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The activity of CA1 neurons in the rodent hippocampus represents multiple aspects of learning episodes, including cue and place information. Previous reports on cue and place representation in CA1 have examined activity in single neurons and population recordings during free exploration of an environment or when actions are directed to either cue or place aspects of memory tasks. To better understand cue and place memory representation in CA1, and how these interact during goal-directed navigation, we investigated population activity in CA1 during memory encoding and retrieval in a novel water task with two visibly distinct platforms, using mRNA for immediate early genes Arc and Homer1a as markers of neural activity. After training, relocating cues to new places induces an extensive, perhaps global, remapping of the memory code that is accompanied by altered navigation and rapid learning of new cue-place information. In addition, we have found a significant relationship between the extent of reactivation and overall cue choice accuracy. These findings demonstrate an important relationship between population remapping in CA1 and memory-guided behavior., (© 2018 Wiley Periodicals, Inc.)

Objectives: To assess the feasibility, safety, and initial estimates of efficacy of a yoga program in postoperative care for women at high risk for breast cancer-related lymphedema (BCRL)., Design: Single-group pretest-post-test design., Settings/location: Patients were recruited from the University of California, San Francisco Carol Franc Buck Breast Care Center., Subjects: Twenty-one women were enrolled in the study. Women were >18 years of age, had undergone surgical treatment for breast cancer, and were at high risk for BCRL., Intervention: The women participated in an Ashtanga yoga intervention for 8 weeks. Sessions consisted of once/week instructor-led practice and once/week home practice. Particular attention was given to poses that emphasized upper body strength and flexibility, while avoiding significant time with the upper extremity (UE) in a dependent position., Outcome Measures: UE volume was assessed through circumferential forearm measurement, which was converted to volume using the formula for a truncated cone. Range of motion (ROM) was assessed for the shoulders, elbows, and wrists, using a standard goniometer. UE strength was assessed for shoulder abduction, elbow flexion, wrist flexion, and grip using a dynamometer., Results: Twenty women completed the yoga intervention, with 17 returning for final assessment. Mean age was 52 (±9.1) years and body mass index was 24.8 (±5.1) kg/m 2 . Postintervention, mean volume in the at-risk UE was slightly reduced (p = 0.397). ROM for shoulder flexion (p < 0.01) and external rotation (p < 0.05) significantly increased bilaterally. Shoulder abduction ROM significantly improved for the unaffected limb (p = 0.001). Following intervention, strength improved on the affected side for shoulder abduction and grip strength, and bilaterally for elbow flexion (p < 0.05 for all)., Conclusions: These preliminary findings suggest that yoga is feasible and safe for women who are at risk for BCRL and may result in small improvements in shoulder ROM and UE strength.

There is a substantial body of evidence that the hippocampus (HPC) plays and essential role in context discrimination in rodents. Studies reporting anterograde amnesia (AA) used repeated, alternating, distributed conditioning and extinction sessions to measure context fear discrimination. In addition, there is uncertainty about the extent of damage to the HPC. Here, we induced conditioned fear prior to discrimination tests and rats sustained extensive, quantified pre- or post-training HPC damage. Unlike previous work, we found that extensive HPC damage spares context discrimination, we observed no AA. There must be a non-HPC system that can acquire long-term memories that support context fear discrimination. Post-training HPC damage caused retrograde amnesia (RA) for context discrimination, even when rats are fear conditioned for multiple sessions. We discuss the implications of these findings for understanding the role of HPC in long-term memory., (© 2017 Wiley Periodicals, Inc.)

Evidence from clinical and animal research highlights the role of the hippocampus in long-term memory (LTM). Decades of experimental work have produced numerous theoretical accounts of the hippocampus in LTM, and each suggests that hippocampal disruption produces amnesia for specific categories of memory. These accounts also imply that hippocampal disruption before or soon after a learning episode should have equivalent amnestic effects. Recent evidence from lesion and inactivation experiments in rodents illustrates that hippocampal disruption after a learning episode causes memory impairment in a wider range of memory tasks than if the same disruption occurs before learning. Although this finding supports that multiple circuits can acquire and retrieve similar information, it also suggests they do not do so independently. In addition, damage after learning produces amnesia for simple elements of a task as well as complex, conjunctive features. Here we develop an explanation for why anterograde and retrograde hippocampal effects differ. This explanation, the heterarchic reinstatement view, also generates novel predictions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To compare the effects of resistance and cardiovascular exercise on functional mobility in individuals with advanced cancer., Design: Prospective, 2-group pretest-posttest pilot study with randomization to either resistance or cardiovascular exercise mode., Setting: Comprehensive community cancer center and a hospital-based fitness facility., Participants: Volunteer sample of individuals (N=66; 30 men; 36 women; mean age, 62y) with advanced cancer recruited through the cancer center, palliative care service, rehabilitation department, and a local hospice., Interventions: Ten weeks of individualized resistance or cardiovascular exercise, prescribed and monitored by oncology-trained exercise personnel., Main Outcome Measures: Functional mobility was assessed using the Short Physical Performance Battery (SPPB); self-reported pain and fatigue were assessed secondarily using visual analog scales. Data were analyzed using a split plot 2×2 analysis of variance (α=.05)., Results: Fifty-two patients (78.8%) completed the study: 23 (67.7%) of 34 patients in the resistance arm and 29 (90.6%) of 32 patients in the cardiovascular arm. No participant withdrew because of study adverse events. Ten-week outcomes (n=52) included a significant increase in SPPB total score (P<.001), increase in gait speed (P=.001), and reduction in fatigue (P=.05). Although cardiovascular exercise participants had a modestly greater improvement in SPPB total score than resistance training participants (F1,49=4.21, P=.045), the difference was not confirmed in a subsequent intention-to-treat analysis (N=66)., Conclusions: Individuals with advanced cancer appear to benefit from exercise for improving functional mobility. Neither resistance nor cardiovascular exercise appeared to have a strong differential effect on outcome., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine if therapist supervision of an exercise program produced better functional outcomes in allogeneic stem cell transplant patients than a patient-directed exercise program., Methods: Sixty-one patients who were less than 6 months post allogeneic stem cell transplant were randomly assigned to either a therapist supervised training group (supervised) or a patient-directed training group (Self-directed). Training consisted of aerobic exercises (treadmill, bicycle ergometer versus walking) and resistance exercises (free weights, weight machines versus resistive band activities). Subjects completed physical performance tests (50-foot fast walk, 6-min walk, forward reach, repeated sit-to-stand, uniped stance) and the Brief Fatigue Inventory (BFI) before and after 4 weeks of training. Pre- and post-training outcomes and group differences were analyzed by a Student t-test., Results: Patients in both groups were similarly deconditioned at baseline. Training increased the 6-min walk distance and 50-foot walk in the supervised group by 12 and 14%, respectively, and increased the 6-min walk distance by 10% in the Self-directed group (p<0.05). BFI score for worst level of fatigue declined in both groups but not significantly., Conclusions: These results demonstrate that allogeneic transplant patients derive functional benefits from short-term exercise training regardless of how the training program is supervised. Determining (1) the reasons for the low participation rate (28%), (2) the patient-preferred characteristics of each exercise supervision style and (3) how best to match patient preference to exercise supervision style remain significant issues in this area of patient delivery services., ((c) 2008 John Wiley & Sons, Ltd.)

To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, we have prepared human C3/CVF hybrid proteins, in which the C-terminus of the alpha-chain of human C3 is exchanged with homologous regions of the C-terminus of the beta-chain of CVF. We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. Human C3/CVF hybrid proteins represent a novel class ofbiologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis.

Objectives: To describe and compare physical performance profiles in men and women with lymphoma with age- and gender-matched controls and to examine relationships among fatigue severity and physical performance in men and women with lymphoma., Design: Case-control study., Setting: Outpatient lymphoma service in a major cancer teaching hospital., Participants: Fifty-one patients with lymphoma (26 women, 25 men), age- and gender-matched to 51 subjects without lymphoma., Interventions: Not applicable., Main Outcome Measures: A physical performance test battery consisting of a 50-ft (15-m) walk, a 6-minute walk, forward reach, repeated sit-to-stand, repeated reach-up, timed belt tie, sock test, and coin test. Patients also completed the Brief Fatigue Inventory (BFI)., Results: Multivariate analysis of variance was significant for main effects of group (F(8,89)=27.12, P<.05) and gender (F(8,89)=3.09, P<.05), and there was no significant interaction. Subsequent analyses found significant differences between groups and gender in the repeated reach-up task, forward reach, 50-ft walk, and distance walked in 6 minutes. Correlations among physical performance tasks and total BFI interference scores were moderate (r range,.27-.43; P<.05) for tasks involving upper extremity, and stronger (r range,.51 to -.73; P<.05) for tasks that involved whole-body movements., Conclusion: There is a leveling effect of lymphoma across gender on most tasks. The significant relations between physical performance tasks and fatigue are suggestive of the pervasive influence of fatigue on physical function.

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer., (Copyright 2001 Cancer Research Campaign.)