The value of source data verification in a cancer clinical trial

Background Source data verification (SDV) is a resource intensive method of quality assurance frequently used in clinical trials. There is no empirical evidence to suggest that SDV would impact on comparative treatment effect results from a clinical trial. Methods Data discrepancies and comparative treatment effects obtained following 100% SDV were compared to those based on data without SDV. Overall survival (OS) and Progression-free survival (PFS) were compared using Kaplan-Meier curves, log-rank tests and Cox models. Tumour response classifications and comparative treatment Odds Ratios (ORs) for the outcome objective response rate, and number of Serious Adverse Events (SAEs) were compared. OS estimates based on SDV data were compared against estimates obtained from centrally monitored data. Findings Data discrepancies were identified between different monitoring procedures for the majority of variables examined, with some variation in discrepancy rates. There were no systematic patterns to discrepancies and their impact was negligible on OS, the primary outcome of the trial (HR (95% CI): 1.18(0.99 to 1.41), p = 0.064 with 100% SDV; 1.18(0.99 to 1.42), p = 0.068 without SDV; 1.18(0.99 to 1.40), p = 0.073 with central monitoring). Results were similar for PFS. More extreme discrepancies were found for the subjective outcome overall objective response (OR (95% CI): 1.67(1.04 to 2.68), p = 0.03 with 100% SDV; 2.45(1.49 to 4.04), p = 0.0003 without any SDV) which was mostly due to differing CT scans. Interpretation Quality assurance methods used in clinical trials should be informed by empirical evidence. In this empirical comparison, SDV was expensive and identified random errors that made little impact on results and clinical conclusions of the trial. Central monitoring using an external data source was a more efficient approach for the primary outcome of OS. For the subjective outcome objective response, an independent blinded review committee and tracking system to monitor missing scan data could be more efficient than SDV

Survival of Lactobacillus sakei during heating, drying and storage in the dried state when growth has occurred in the presence of sucrose or monosodium glutamate

Spray-dried cells of Lactobacillus sakei CTC 494 survived ca. 60% longer in the spray dried state when cells were grown in the presence of 20 g sucrose l)1 or 12.5 g monosodium glutamate l)1. No significant differences were observed in viability during storage in the freeze dried state with the addition of these compounds to the growth medium, nor in survival during a heat treatment (55ºC). Both sucrose and glutamate in the growth medium suppressed intracellular accumulation of total amino acids and changed the overall pattern of the individual amino acids. Glutamate in the growth medium enhanced intracellular glutamate by ca. 38

Proposal to produce long-lived mesoscopic superpositions through an atom-driven field interaction

We present a proposal for the production of longer-lived mesoscopic superpositions which relies on two requirements: parametric amplification and squeezed vacuum reservoir for cavity-field states. Our proposal involves the interaction of a two-level atom with a cavity field which is simultaneously subjected to amplification processes.Comment: 12 pages, title changed, text improved and refences adde

Improving the delivery and efficiency of fungus-impregnated cloths for control of adult Aedes aegypti using a synthetic attractive lure

Abstract Background Entomopathogenic fungi are highly promising agents for controlling Aedes aegypti mosquitoes. Deploying fungus-impregnated black cloths in PET traps efficiently reduced Ae. aegypti female survival rates under intra-domicile conditions. With the aim of further increasing the effectiveness of the traps, the addition of attractive lures to fungus-impregnated traps was evaluated. Methods Black cloths were suspended inside 2 l plastic bottles called “PET traps”. These traps were placed in rooms simulating human residences. The first experiments evaluated the attraction of mosquitoes to PET traps with black cloths covered in adhesive film with and without synthetic lures (AtrAedes™). Traps were left in the test rooms for either 24 or 48 h. The attractiveness of the lures over time was also evaluated. The efficiency of PET traps with fungus-impregnated black cloths associated with lures was compared to that of traps without lures. Results The highest percentage of captured mosquitoes (31 and 66%) were observed in PET traps with black cloths covered in adhesive film + attractive lure maintained in test rooms for 24 h and 48 h, respectively. Black cloths covered in adhesive film captured 17 or 36% of the mosquitoes at 24 h and 48 h, respectively. The attractiveness of the lures fell gradually over time, capturing 37% after 5 days on the bench and 22% of the mosquitoes after 30 days exposure to ambient conditions. Associating attractive synthetic lures with black cloths impregnated with M. anisopliae placed in test rooms for 120 h reduced mean survival to 32%, whilst black cloths impregnated with M. anisopliae without lures resulted in a 48% survival rate. Using Beauveria bassiana in the traps resulted in a 52% reduction in mosquito survival, whilst combining Beauveria and AtrAedes resulted in a 36% survival rate. PET traps impregnated with fungus + AtrAedes resulted in similar reductions in survival when left in the rooms for 24, 48, 72 or 120 h. Conclusions AtrAedes increased attractiveness of PET traps with black cloths under intra-domicile conditions and when associated with M. anisopliae or B. bassiana, significantly reduced Aedes survival. This strategy will reduce the number of PET traps necessary per household

New formulation of an old drug in hypertension treatment: the sustained release of captopril from cyclodextrin nanoparticles

Captopril (CAP) was the first angiotensin I-converting enzyme (ACE) inhibitor to be developed and is widely used in hypertension treatment. On the other hand, cyclodextrins (CDs) are cyclic oligosaccharides whose cone-shaped cavity allows formation of noncovalent inclusion complexes with appropriately sized guest molecules, thus modifying guest physical, chemical, and biological properties. Herein, the physicochemical characterization and in vivo ACE inhibition evaluation of seven CAP/CD complexes are reported. The inclusion complexes were prepared by spray-drying, freeze-drying, kneading, or lyophilization methods and characterized by nuclear magnetic resonance, Fourier-transformed infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy techniques. In vivo assays compared CAP and CAP/CD complex administration (0.5 mg kg−1 or 0.09 mg kg−1, n = 4–7) to evaluate the ACE inhibition by continuous infusion of angiotensin I (30 ng 50 μL−1 min−1) in conscious Wistar rats. The physicochemical analysis demonstrated complete amorphization and complexation between CAP and CDs, indicating the substitution of water molecules inside the CD cavity with CAP. During the infusion of angiotensin I, the administration of all CAP/CD complexes induced a reduction in mean arterial pressure similar to that observed upon CAP administration. The nanoparticles obtained by the kneading method (CAP/α-CD:KM) showed a potent and long-lasting inhibitory activity (∼22 hours) on the angiotensin I pressor effect. The results suggest that the inclusion complex of CAP and α-CD can function as a novel antihypertensive formulation that may improve therapeutic use of CAP by reducing its oral dose administration to once per day, thus providing better quality of life for almost 25% of the world’s population who suffer from hypertension

Impact of promoting self-care in nursing workload

Abstract OBJECTIVES To assess the impact of promoting self-care in nursing workload and associate it to the variables: age, gender, socioeconomic status, education, marital status and number of children of caregivers. METHODS Prospective study with 31 children and their caregivers. Participants were assessed at two moments, 1st and 2nd hospitalization, the nursing workload was measured by the Nursing Activities Score (NAS). RESULTS The mean NAS in the 1st hospitalization was 60.9% and in the 2nd hospitalization was 41.6%, that is, 14.6 and 9.9 hours of nursing, respectively. The nursing workload on the first day of hospitalization was higher compared to the last day, both for the 1st (p<0.001) and for the 2nd hospitalization (p<0.001), and higher in the first (p<0.001) and in the last day (p=0.025) in the 1st hospitalization. Comparing the 1st hospitalization to the 2nd hospitalization, the first was higher (p<0.001), and NAS items related to the training of self-care was influenced (p<0.001). CONCLUSION The nursing workload associated to self-care promotion corresponded to 14.6 hours and was higher than determined by the existing legislation

Diagnósticos de enfermagem identificados em pacientes internados em Unidade de Terapia Intensiva Adulto

Estudo descritivo para identificar nos registros de prontuários de pacientes internados em uma Unidade de Terapia Intensiva de Adultos os diagnósticos de enfermagem e mapear os diagnósticos mais frequentes às Necessidades Humanas Básicas. Obteve-se uma amostra de 44 prontuários. Identificaram-se 1.087 diagnósticos de enfermagem. Após exclusão de repetições, encontraram-se 28 diferentes títulos de diagnósticos. Vinte e cinco diagnósticos estavam relacionados às necessidades psicobiológicas, e três, às necessidades psicossociais. Sugere-se a realização de estudos que identifiquem, entre os diagnósticos de enfermagem formulados e as necessidades humanas afetadas, quais foram solucionados e para quais necessidades são predominantemente elaborados os cuidados. Os resultados deste estudo são importantes para a organização de conteúdos de ensino para alunos e enfermeiros, preparando-os para que, ao prestar o cuidado, considerem o ser humano, tanto nos aspectos biológicos, como emocionais e espirituais

Cell arrest and cell death in mammalian preimplantation development

The causes, modes, biological role and prospective significance of cell death in preimplantation development in humans and other mammals are still poorly understood. Early bovine embryos represent a very attractive experimental model for the investigation of this fundamental and important issue. To obtain reference data on the temporal and spatial occurrence of cell death in early bovine embryogenesis, three-dimensionally preserved embryos of different ages and stages of development up to hatched blastocysts were examined in toto by confocal laser scanning microscopy. In parallel, transcript abundance profiles for selected apoptosis-related genes were analyzed by real-time reverse transcriptase-polymerase chain reaction. Our study documents that in vitro as well as in vivo, the first four cleavage cycles are prone to a high failure rate including different types of permanent cell cycle arrest and subsequent non-apoptotic blastomere death. In vitro produced and in vivo derived blastocysts showed a significant incidence of cell death in the inner cell mass (ICM), but only in part with morphological features of apoptosis. Importantly, transcripts for CASP3, CASP9, CASP8 and FAS/FASLG were not detectable or found at very low abundances. In vitro and in vivo, errors and failures of the first and the next three cleavage divisions frequently cause immediate embryo death or lead to aberrant subsequent development, and are the main source of developmental heterogeneity. A substantial occurrence of cell death in the ICM even in fast developing blastocysts strongly suggests a regular developmentally controlled elimination of cells, while the nature and mechanisms of ICM cell death are unclear. Morphological findings as well as transcript levels measured for important apoptosis-related genes are in conflict with the view that classical caspase-mediated apoptosis is the major cause of cell death in early bovine development