First and second eye cataract surgery and driver self-regulation among older drivers with bilateral cataract: A prospective cohort study

Background: Driving a car is the most common form of transport among the older population. Common medical conditions such as cataract, increase with age and impact on the ability to drive. To compensate for visual decline, some cataract patients may self-regulate their driving while waiting for cataract surgery. However, little is known about the self-regulation practices of older drivers throughout the cataract surgery process. The aim of this study is to assess the impact of first and second eye cataract surgery on driver self-regulation practices, and to determine which objective measures of vision are associated with driver self-regulation. Methods: Fifty-five older drivers with bilateral cataract aged 55+ years were assessed using the self-reported Driving Habits Questionnaire, the Mini-Mental State Examination and three objective visual measures in the month before cataract surgery, at least one to three months after first eye cataract surgery and at least one month after second eye cataract surgery. Participants' natural driving behaviour in four driving situations was also examined for one week using an in-vehicle monitoring device. Two separate Generalised Estimating Equation logistic models were undertaken to assess the impact of first and second eye cataract surgery on driver-self-regulation status and which changes in visual measures were associated with driver self-regulation status. Results: The odds of being a self-regulator in at least one driving situation significantly decreased by 70% after first eye cataract surgery (OR: 0.3, 95% CI: 0.1-0.7) and by 90% after second eye surgery (OR: 0.1, 95% CI: 0.1-0.4), compared to before first eye surgery. Improvement in contrast sensitivity after cataract surgery was significantly associated with decreased odds of self-regulation (OR: 0.02, 95% CI: 0.01-0.4). Conclusions: The findings provide a strong rationale for providing timely first and second eye cataract surgery for older drivers with bilateral cataract, in order to improve their mobility and independence

APOMAB®, a La-Specific Monoclonal Antibody, Detects the Apoptotic Tumor Response to Life-Prolonging and DNA-Damaging Chemotherapy

Background: Antineoplastic therapy may impair the survival of malignant cells to produce cell death. Consequently, direct measurement of tumor cell death in vivo is a highly desirable component of therapy response monitoring. We have previously shown that APOMAB® representing the DAB4 clone of a La/SSB-specific murine monoclonal autoantibody is a malignant cell-death ligand, which accumulates preferentially in tumors in an antigen-specific and dose-dependent manner after DNA-damaging chemotherapy. Here, we aim to image tumor uptake of APOMAB® (DAB4) and to define its biological correlates. Methodology/Principal Findings: Brisk tumor cell apoptosis is induced in the syngeneic EL4 lymphoma model after treatment of tumor-bearing mice with DNA-damaging cyclophosphamide/etoposide chemotherapy. Tumor and normal organ accumulation of Indium 111 (111In)-labeled La-specific DAB4 mAb as whole IgG or IgG fragments was quantified by whole-body static imaging and organ assay in tumor-bearing mice. Immunohistochemical measurements of tumor caspase-3 activation and PARP-1 cleavage, which are indicators of early and late apoptosis, respectively, were correlated with tumor accumulation of DAB4. Increased tumor accumulation of DAB4 was associated directly with both the extent of chemotherapy-induced tumor cell death and DAB4 binding per dead tumor cell. Tumor DAB4 accumulation correlated with cumulative caspase-3 activation and PARP-1 cleavage as tumor biomarkers of apoptosis and was directly related to the extended median survival time of tumor-bearing mice. Conclusions/Significance: Radiolabeled La-specific monoclonal antibody, DAB4, detected dead tumor cells after chemotherapy, rather than chemosensitive normal tissues of gut and bone marrow. DAB4 identified late apoptotic tumor cells in vivo. Hence, radiolabeled DAB4 may usefully image responses to human carcinoma therapy because DAB4 would capture the protracted cell death of carcinoma. We believe that the ability of radiolabeled DAB4 to rapidly assess the apoptotic tumor response and, consequently, to potentially predict extended survival justifies its future clinical development as a radioimmunoscintigraphic agent. This article is part I of a two-part series providing proof-of-concept for the the diagnostic and therapeutic use of a La-specific monoclonal antibody, the DAB4 clone of which is represented by the registered trademark, APOMAB®.Fares Al-Ejeh, Jocelyn M. Darby, Chris Tsopelas, Douglas Smyth, Jim Manavis and Michael P. Brow

Stakeholders' views and experiences of care and interventions for addressing frailty and pre-frailty:a meta-synthesis of qualitative evidence

Frailty is a common condition in older age and is a public health concern which requires integrated care and involves different stakeholders. This meta-synthesis focuses on experiences, understanding, and attitudes towards screening, care, intervention and prevention for frailty across frail and healthy older persons, caregivers, health and social care practitioners. Studies published since 2001 were identified through search of electronic databases; 81 eligible papers were identified and read in full, and 45 papers were finally included and synthesized. The synthesis was conducted with a meta-ethnographic approach. We identified four key themes: Uncertainty about malleability of frailty; Strategies to prevent or to respond to frailty; Capacity to care and person and family-centred service provision; Power and choice. A bottom-up approach which emphasises and works in synchrony with frail older people's and their families' values, goals, resources and optimisation strategies is necessary. A greater employment of psychological skills, enhancing communication abilities and tools to overcome disempowering attitudes should inform care organisation, resulting in more efficient and satisfactory use of services. Public health communication about prevention and management of frailty should be founded on a paradigm of resilience, balanced acceptance, and coping. Addressing stakeholders' views about the preventability of frailty was seen as a salient need

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research

Radiologist review versus group peer review of claimed responses in a phase II study on high-dose ifosfamide in advanced soft tissue sarcomas of the adult: a study of the EORTC Soft Tissue and Bone Sarcoma Group

The Soft Tissue and Bone Sarcoma Group (STBSG) of the EORTC ran a phase II study to assess the therapeutic activity of high-dose ifosfamide in patients with advanced soft tissue sarcomas by means of response rate (RR). Investigators claiming a response submitted the relevant chest radiographs (CXR) or scans to two other members of the STBSG for peer review. The reviewers completed a questionnaire indicating overall response or reasons for rejecting the claimed responses. An independent radiologist also reviewed the cases and he was blinded to the results of the peer review until the study was concluded. Twenty-two patients were reviewed by the radiologist and peer review, and the completed questionnaires were retrospectively reviewed. Two differences were noted, one partial responder (PR) was regarded as stable disease by the radiologist and one PR by peer review was determined a complete response by the radiologist. The radiologist found subsequent evidence of progressive disease in three patients who initially showed a PR, whilst the review group noted only one. This study suggests peer review in this tumor type is a satisfactory method of achieving an accurate, objective RR. [(C) 2000 Lippincott Williams & Wilkins]

Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial.

BACKGROUND: In the non-curative setting, the sequence in which anticancer agents are used, singly or in combination, may be important if patients are to receive the maximum period of disease control with the minimum of adverse effects. We compared sequential and combination chemotherapy strategies in patients with unpretreated advanced or metastatic colorectal cancer, who were regarded as not potentially curable irrespective of response. METHODS: We studied patients with advanced colorectal cancer, starting treatment with non-curative intent. 2135 unpretreated patients were randomly assigned to three treatment strategies in the ratio 1:1:1. Strategy A (control group) was single-agent fluorouracil (given with levofolinate over 48 h every 2 weeks) until failure, then single-agent irinotecan. Strategy B was fluorouracil until failure, then combination chemotherapy. Strategy C was combination chemotherapy from the outset. Within strategies B and C, patients were randomly assigned to receive, as the combination regimen, fluorouracil plus irinotecan (groups B-ir and C-ir) or fluorouracil plus oxaliplatin (groups B-ox and C-ox). The primary endpoint was overall survival, analysed by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 79877428. RESULTS: Median survival of patients allocated to control strategy A was 13.9 months. Median survival of each of the other groups was longer (B-ir 15.0, B-ox 15.2, C-ir 16.7, and C-ox 15.4 months). However, log-rank comparison of each group against control showed that only C-ir--the first-line combination strategy including irinotecan--satisfied the statistical test for superiority (p=0.01). Overall comparison of strategy B with strategy C was within the predetermined non-inferiority boundary of HR=1.18 or less (HR=1.06, 90% CI 0.97-1.17). INTERPRETATION: Our data challenge the assumption that, in this non-curative setting, maximum tolerable treatment must necessarily be used first-line. The staged approach of initial single-agent treatment upgraded to combination when required is not worse than first-line combination, and is an alternative option for discussion with patients