Validation of accelerometer placement to capture energy expenditure using doubly labeled water.

This study compared accelerometer-measured physical activity by body placement to daily total energy expenditure (TEE) and activity energy expenditure (AEE) measured using doubly labeled water (DLW). Forty-nine adult participants wore accelerometers placed on the nondominant wrist, dominant wrist, and chest while also undergoing DLW assessments. In adjusted models, wrist-measured physical activity (p < 0.05), but not chest-measured physical activity (p > 0.05), was associated with TEE and AEE and explained a significant amount of variance that was not explained by age, sex, height, or body composition (R2 change = 0.04-0.08; all p < 0.05). Accelerometer placement location is an important consideration when using accelerometry to provide information about energy expenditure.

From symbiont to parasite: the evolution of for-profit science publishing.

Two 17th century institutions-learned societies and scientific journals-transformed science in ways that still dominate our professional lives today. Learned societies like the American Society for Cell Biology remain relevant because they provide forums for sharing results, discussing the practice of science, and projecting our voices to the public and the policy makers. Scientific journals still disseminate our work, but in the Internet-connected world of the 21st century, this is no longer their critical function. Journals remain relevant almost entirely because they provide a playing field for scientific and professional competition: to claim credit for a discovery, we publish it in a peer-reviewed journal; to get a job in academia or money to run a lab, we present these published papers to universities and funding agencies. Publishing is so embedded in the practice of science that whoever controls the journals controls access to the entire profession. We must reform our methods for evaluating the contributions of younger scientists and deflate the power of a small number of "elite" journals. More generally, given the recent failure of research institutions around the world to strike satisfactory deals with publishing giant Elsevier, the time has come to examine the motives and methods of those to whom we have entrusted the keys to the kingdom of science.

Total energy expenditure in patients with colorectal cancer: associations with body composition, physical activity, and energy recommendations.

BACKGROUND: Total energy expenditure (TEE) data in patients with early-stage cancer are scarce, precluding an understanding of energy requirements. OBJECTIVE: The objective was to cross-sectionally characterize TEE in patients with colorectal cancer (CRC) and to compare measured TEE with energy recommendations. It was hypothesized that TEE would differ according to body mass, body composition, and physical activity level (PAL) and current energy recommendations would have poor individual-level accuracy. METHODS: Patients with newly diagnosed CRC had resting energy expenditure (REE) measured by indirect calorimetry and TEE by doubly labeled water. Hypermetabolism was defined as REE > 110% of that predicted from the Mifflin St.-Jeor equation. Body composition was assessed via DXA. Physical activity was determined as the ratio of TEE to REE (TEE:REE) (PAL) and residual activity energy expenditure (RAEE). TEE was compared with energy recommendations of 25-30 kcal/d and Dietary Reference Intakes (DRIs) using Bland-Altman analyses. Patients were stratified according to median BMI, PAL, and sex-specific ratio of fat mass (FM) to fat-free mass (FFM). RESULTS: Twenty-one patients (M:F 14:7; mean ± SD BMI: 28.3 ± 4.9 kg/m2, age: 57 ± 12 y) were included. Most (n = 20) had stage II-III disease; 1 had stage IV. Approximately half (n = 11) were hypermetabolic; TEE was not different in those with hypermetabolism and REE as a percentage of predicted was not correlated with TEE. Mean ± SD TEE was 2473 ± 499 kcal/d (range: 1562-3622 kcal/d), or 29.7 ± 6.3 kcal/kg body weight (range: 20.4-48.5 kcal/kg body weight). Mean ± SD PAL was 1.43 ± 0.27. The energy recommendation of 25 kcal/kg underestimated TEE (-12.6% ± 16.5%, P = 0.002); all energy recommendations had wide limits of agreement (the smallest was DRI with measured PAL: -21.2% to 29.3%). Patients with higher BMI and FM:FFM had higher bias using kilocalories per kilogram recommendations; bias from several recommendations was frequently lower (i.e. underestimation) in patients with higher PAL and RAEE. CONCLUSIONS: TEE variability was not reflected in energy recommendations and error was related to body weight, body composition, and physical activity. This trial was registered at clinicaltrials.gov as NCT03131921.

One-Year Safety and Performance Assessment of the Argus II Retinal Prosthesis: A Postapproval Study.

IMPORTANCE: The Argus II Retinal Prosthesis System is indicated for patients with vision loss due to severe to profound outer retinal degeneration, a group with few treatment options. OBJECTIVES: To collect postapproval safety and visual function data for the Argus II. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, postapproval clinical trial conducted at 9 sites in Germany and Italy. Data were collected from December 2, 2011, to September 30, 2017, and patients were followed-up for 12 months or longer. Patients were 25 years or older with severe to profound outer retinal degeneration, some residual light perception or the ability of the retina to respond to electrical stimulation, and a history of useful form vision and were already planning to undergo Argus II implantation. MAIN OUTCOMES AND MEASURES: The primary end point of this study was the nature and rate of adverse events. Secondary end points included 3 visual function tests: square localization (SL), direction of motion, and grating visual acuity (GVA). RESULTS: Forty-seven patients were followed for 12 months or longer after implant. Mean (SD) age was 56 (12) years, 37 (79%) had retinitis pigmentosa, and 27 (57%) were male. Through the first 12 months postimplantation, 23 patients (49%) experienced 51 nonserious adverse events and 12 (26%) experienced 13 serious adverse events (SAEs), 9 of which were judged to be related to the Argus II, and 4 of which were judged to be related to the procedure. The most common SAE was conjunctival erosion, reported in 4 patients. No significance testing was done for group analysis for the SL or direction-of-motion tests. When averaged across the group, patients' accuracy on the SL test, but not on the direction-of-motion test, appeared better when the Argus II was on than when it was switched off. For GVA, more patients at each point in time achieved the 2.9 GVA cutoff in the implanted eye when the Argus II was on compared with it switched off. CONCLUSIONS AND RELEVANCE: Safety and visual function outcomes in this clinical practice setting cohort of patients with Argus II implants were consistent with previously reported results. Longer follow-up of these patients and data from additional patients are required to better outline the risks and benefits of this approach to addressing blindness secondary to severe-to-profound outer retinal degeneration. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01490827.

Assessment of Corneal Endothelium during Continued Organ Culture of Pre-Stripped Human Donor Tissue for DMEK Surgery.

PURPOSE: To measure corneal endothelial cell (EC) quality and quantity following Descemet membrane (DM) stripping of human donor corneas and continued storage in organ culture medium containing dextran. METHODS: DM stripping was performed in 30 organ cultured, corneoscleral discs. Corneas were divided into 3 groups of 10 corneas each. Baseline mean EC density (cells/mm2) was 2,372 (SD ± 259) in group 1, 2,540 (SD ± 266) in group 2, and 2,665 (SD ± 263) in group 3. Following subtotal DM stripping, culture was continued at 31°C for 24 hours (group 1), 72 hours (group 2), and 120 hours (group 3), respectively. EC density was measured before stripping and at the end of culture. At the end of culture, corneal EC morphology was graded using a scoring system and EC viability was measured by detection of adenosine triphosphate. RESULTS: At the end of culture, mean EC density was 2,159 (SD ± 293) in group 1, 1,946 (SD ± 182) in group 2, and 2,047 (SD ± 225) in group 3. This constitutes an EC loss of 9,1% (SD ± 5,3%) in group 1, 23,0 % (SD ± 6,5%) in group 2, and 22,7% (SD ± 9,1%) in group 3 (p < 0.001). After completion of follow-up, all groups contained corneas with EC counts < 2,000 cells/mm2. Cell morphology scores did not differ between the three experimental groups. EC viability measurements showed a tendency toward lower readings with extended length of culture. CONCLUSIONS: Corneal EC loss does occur following DM stripping and continued organ culture. EC loss increases with storage past 24 hours, but donor corneas may fall below 2,000 cells/mm2 independently of storage duration. The use of eye bank prepared donor lamellae for Descemet Membrane Endothelial Keratoplasty (DMEK) may increase patient safety by offering standardized quality control before tissue release.

The role of corneal endothelial morphology in graft assessment and prediction of endothelial cell loss during organ culture of human donor corneas.

PURPOSE: Endothelial assessment is crucial in the release of corneas for grafting. We retrospectively analysed the role of endothelial morphology parameters in predicting endothelial cell loss during organ culture. METHODS: Human donor corneas were cultured in minimal essential medium with 2% fetal calf serum and antibiotics. Initial endothelial morphology was assessed microscopically using score parameters polymegethism (POL), pleomorphism (PLE), granulation (GRA), vacuolization (VAC), segmentation of cell membranes (SEG), Descemet's folds (DF), trypan blue-positive cells (TBPC) and endothelial cell-free areas (ECFA). Some corneas were primarily rejected based on endothelial assessment. Endothelial cell density (ECD) was assessed at the beginning (I-ECD) and end of culture. Corneas were then placed in dehydration medium (as above + 5% dextran 500). In a subgroup, ECD was reassessed after dehydration. Endothelial cell loss during culture (ECL@Culture) and culture+dehydration (ECL-Culture&Dehydration) were calculated. Data were given as mean ± SD and analysed using multiple linear and logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULT: I-ECD was 2812 ± 360/mm2 (n = 2356). The decision to reject a cornea due to endothelial assessment was associated negatively with I-ECD (OR = 0.77/100 cells, CI 0.7-0.82) and positively with ECFA (OR = 2.7, CI 1.69-4.35), SEG (OR =1.3, CI 1.01-1.68) and donor age (OR = 1.26/decade, CI 1.33-1.41). ECL@Culture was 153 ± 201/mm2 (n = 1277), ECL@Culture&Dehydration was 169 ± 183/mm2 (n = 918). ECL@Culture was associated positively with donor age, I-ECD, GRA and TBPC, and negatively with PLE, and DF. ECL@Culture&Dehydration was associated positively with age, sex, initial ECD, POL, PLE, VAC and TBPC. CONCLUSION: Morphological parameters displayed associations with the exclusion of corneas from culture and with endothelial cell loss. Appropriate parameter selection for screening purposes may help improve graft quality.

Financial burden and quality of life of informal caregivers of patients with wet age-related macular degeneration.

PURPOSE: The purpose of this research is to quantify the cost burden, care times and the impact on the quality of life (QoL) of informal caring relatives caring for patients with wet age-related macular degeneration (wet AMD). Moreover we investigated the impact of care times on the QoL. METHODS: Through a specifically designed questionnaire, 150 caring relatives were interviewed retrospectively on all accrued financial costs, caring times incurred and the current QoL, assessed by a Visual Analogue Scale for happiness (VAS). RESULTS: The caring time incurred was on average 6.4 ± 8.5 (mean +/- SD) hours per week. The QoL was on average rated at 6.7 ± 1.9 on a ten point scale. Financial strain was incurred by the direct non-medical costs of on average € 405 ± 1104 and the direct medical costs of on average € 134 ± 340 per year. Indirect costs were stated by two caregivers as amounting to € 2400 and € 6000 net income loss per year respectively. Caregivers of privately insured patients with wet AMD carried a financial cost burden which was up to six times higher than caregivers of patients who were on state insurance while showing the same visual acuity. CONCLUSION: The evaluation shows that caregivers of privately insured patients with wet AMD have higher costs than caregivers of patients with state insurance coverage. This burden seems to be a factor to be considered independently since it does not appear to have any relation to patients AMD acuity.

Conjunctival and intraocular swabs for the microbiological assessment of donor corneas.

PURPOSE: In this study, we investigated the associations between conjunctival (co) and intraocular (io) swabs and their implications for the contamination rates of organ-cultured corneas. METHODS: A total of 4177 swabs from 1054 corneas of 527 donors were acquired from the conjunctiva, after disinfection with 5% polyvinylpyrrolidone-iodine solution, and also from the anterior chamber after corneoscleral trepanation (io). Samples were incubated at 22.5 ± 2.5°C and 32.5 ± 2.5°C in thioglycollate broth for 14 days. Donor corneas were cultured in a closed system at 31°C. Microbial differentiation was performed for positive cultures. RESULTS: A higher temperature (32.5°C) and the intraocular swab retrieving localization led to significantly higher swab positive rates (32.5°C versus 22.5°C, odds 1.65, p < 0.0001; io versus co, odds 1,53, p < 0.0001). Death-to-collection time and laterality (left or right eye) had no significant influence on swab positivity. The cause of death significantly influenced the positive rates (p < 0.0001). Detection at 32.5°C occurred significantly earlier than at 22.5°C (p < 0.0001). The overall comparison of detected species showed no significant differences in the variety between intraocular and conjunctival swabs. During the study period, six contaminations of organ-cultured corneas occurred: four times Pseudomonas aeruginosa and once each Candida albicans and Staphylococcus hominis were found. Swap results and cornea contaminations were not significantly correlated. CONCLUSIONS: Co and io swabs show high microbial colonization rates, even after standard disinfection. Io swabs generally reproduce the co microbial range, most likely due to a mobilization and diversion of microorganisms during the trepanation procedure. Swab results do not yield a valuable tool to predict contaminations of organ-cultured corneas.

The cost-effectiveness of the Argus II retinal prosthesis in Retinitis Pigmentosa patients.

BACKGROUND: Retinitis Pigmentosa (RP) is a hereditary genetic disease causing bilateral retinal degeneration. RP is a leading cause of blindness resulting in incurable visual impairment and drastic reduction in the Quality of life of the patients. Second Sight Medical Products Inc. developed Argus II, a retinal prosthesis system for treating RP. Argus II is the world's first ever-commercial implant intended to restore some vision in the blind patients. The objective of this study was to assess the cost-effectiveness of the Argus® II Retinal Prosthesis System (Argus II) in Retinitis Pigmentosa (RP) patients. METHOD: A multi -state transition Markov model was developed to determine the cost-effectiveness of Argus II versus usual care in RP from the perspective of healthcare payer. A hypothetical cohort of 1000 RP patients aged 46 years followed up over a (lifetime) 25-year time horizon. Health outcomes were expressed as quality adjusted life years (QALYs) and direct healthcare costs expressed in 2012 €. Results are reported as incremental cost per ratios (ICERs) with outcomes and costs discounted at an annual rate of 3.5%. RESULTS: The ICER for Argus II was €14,603/QALY. Taking into account the uncertainty in model inputs the ICER was €14,482/QALY in the probabilistic analysis. In the scenarios of an assumption of no reduction on cost across model visual acuity states or a model time horizon as short as 10 years the ICER increased to €31,890/QALY and €49,769/QALY respectively. CONCLUSION: This economic evaluation shows that Argus II is a cost-effective intervention compared to usual care of the RP patients. The lifetime analysis ICER for Argus II falls below the published societal willingness to pay of EuroZone countries.

Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment study (SPR study): Risk assessment of anatomical outcome. SPR study report no. 7.

PURPOSE: The 'Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment study' (SPR study) is a randomized multicentre trial comparing primary vitrectomy (PV) and scleral buckling surgery (SB) for rhegmatogenous retinal detachment (RRD). This subanalysis was conducted to identify risk factors associated with anatomical outcomes. METHODS: Relating the anatomical success results at the 1-year follow-up visit to pre- and intraoperative findings using multivariate statistical methods. RESULTS: In the phakic subtrial, anatomical success was negatively associated with the number of breaks (p < 0.0001), break extension > 1 clock hour (p = 0.0005) and intraoperative use of cryotherapy (p = 0.0484). It was positively associated with retinal breaks with irregular edges (p = 0.0353) and subretinal fluid drainage (p = 0.0155). In the pseudophakic/aphakic subtrial, anatomical success was negatively associated with the number of retinal breaks (p = 0.0004) and previous YAG capsulotomy (p = 0.0256), and the combined effect of the surgical procedure and intraoperative use of laser (p = 0.0229). CONCLUSION: Primary anatomical success is an important result for patients undergoing RRD surgery. Our data demonstrate that the final anatomical outcome is related to a higher preoperative number of breaks and cryotherapy in phakic eyes. Additional risk factors varied between phakic and pseudophakic subgroups. Our findings may be used to facilitate the prognosis of future patients with RRD.

A method and technical equipment for an acute human trial to evaluate retinal implant technology.

This paper reports on methods and technical equipment to investigate the epiretinal stimulation of the retina in blind human subjects in acute trials. Current is applied to the retina through a thin, flexible microcontact film (microelectrode array) with electrode diameters ranging from 50 to 360 microm. The film is mounted in a custom-designed surgical tool that is hand-held by the surgeon during stimulation. The eventual goal of the work is the development of a chronically implantable retinal prosthesis to restore a useful level of vision to patients who are blind with outer retinal degenerations, specifically retinitis pigmentosa and macular degeneration.