Relationships Among Neonatal Mortality, Hospital Volume, Weekday Demand, and Weekend Birth.

Background Research findings indicate that hospital volume affects the quality of care, that quality and demand for care on weekends differs from weekdays, and that giving birth on the weekend increases odds of neonatal mortality. Purpose To explore relationships among neonatal mortality, hospital volume, weekday demand for services, and weekend birth and risk of neonatal mortality. Methods For this retrospective, population-based, cohort study design, data were obtained from 32,140 electronic birth certificate records matched with 92 death certificate records from the Texas Department of State Health Services for 2012. Statistical analyses include descriptive procedures, analysis of variance, bivariate correlation, t-test, logistic regression, and chi-square tests of association. Results Higher hospital birth volume and higher concentrations of births during the week were associated with fewer neonatal deaths. Weekend births were associated not only with higher rates of neonatal death but also with lower birth weight and ethnicity of the mother. Conclusions These findings suggest the need for further study of the ways hospital-level organization of services and resources interact with individual risk factors to play a significant role in raising the neonatal mortality risk associated with weekend birth.

Perineuronal nets labeled by monoclonal antibody VC1.1 ensheath interneurons expressing parvalbumin and calbindin in the rat amygdala.

Perineuronal nets (PNNs) are specialized condensations of extracellular matrix that ensheath particular neuronal subpopulations in the brain and spinal cord. PNNs regulate synaptic plasticity, including the encoding of fear memories by the amygdala. The present immunohistochemical investigation studied PNN structure and distribution, as well as the neurochemistry of their ensheathed neurons, in the rat amygdala using monoclonal antibody VC1.1, which recognizes a glucuronic acid 3-sulfate glycan associated with PNNs in the cerebral cortex. VC1.1+ PNNs surrounded the cell bodies and dendrites of a subset of nonpyramidal neurons in cortex-like portions of the amygdala (basolateral amygdalar complex, cortical nuclei, nucleus of the lateral olfactory tract, and amygdalohippocampal region). There was also significant neuropilar VC1.1 immunoreactivity, whose density varied in different amygdalar nuclei. Cell counts in the basolateral nucleus revealed that virtually all neurons ensheathed by VC1.1+ PNNs were parvalbumin-positive (PV+) interneurons, and these VC1.1+/PV+ cells constituted 60% of all PV+ interneurons, including all of the larger PV+ neurons. Approximately 70% of VC1.1+ neurons were calbindin-positive (CB+), and these VC1.1+/CB+ cells constituted about 40% of all CB+ neurons. Colocalization of VC1.1 with Vicia villosa agglutinin (VVA) binding, which stains terminal N-acetylgalactosamines, revealed that VC1.1+ PNNs were largely a subset of VVA+ PNNs. This investigation provides baseline data regarding PNNs in the rat which should be useful for future studies of their function in this species.

Monitoring and Targeting Anti-VEGF Induced Hypoxia within the Viable Tumor by 19F-MRI and Multispectral Analysis.

The effect of anti-angiogenic agents on tumor oxygenation has been in question for a number of years, where both increases and decreases in tumor pO2 have been observed. This dichotomy in results may be explained by the role of vessel normalization in the response of tumors to anti-angiogenic therapy, where anti-angiogenic therapies may initially improve both the structure and the function of tumor vessels, but more sustained or potent anti-angiogenic treatments will produce an anti-vascular response, producing a more hypoxic environment. The first goal of this study was to employ multispectral (MS) 19F-MRI to noninvasively quantify viable tumor pO2 and evaluate the ability of a high dose of an antibody to vascular endothelial growth factor (VEGF) to produce a strong and prolonged anti-vascular response that results in significant tumor hypoxia. The second goal of this study was to target the anti-VEGF induced hypoxic tumor micro-environment with an agent, tirapazamine (TPZ), which has been designed to target hypoxic regions of tumors. These goals have been successfully met, where an antibody that blocks both murine and human VEGF-A (B20.4.1.1) was found by MS 19F-MRI to produce a strong anti-vascular response and reduce viable tumor pO2 in an HM-7 xenograft model. TPZ was then employed to target the anti-VEGF-induced hypoxic region. The combination of anti-VEGF and TPZ strongly suppressed HM-7 tumor growth and was superior to control and both monotherapies. This study provides evidence that clinical trials combining anti-vascular agents with hypoxia-activated prodrugs should be considered to improved efficacy in cancer patients.

The impact of rationing of health resources on capacity of Australian public sector nurses to deliver nursing care after-hours: a qualitative study.

Australia, along with other countries, has introduced New Public Management (NPM) into public sector hospitals in an effort to contain healthcare costs. NPM is associated with outsourcing of service provision, the meeting of government performance indicators, workforce flexibility and rationing of resources. This study explores the impact of rationing of staffing and other resources upon delivery of care outside of business hours. Data was collected through semistructured interviews conducted with 21 nurses working in 2 large Australian metropolitan hospitals. Participants identified four strategies associated with NPM which add to workload after-hours and impacted on the capacity to deliver nursing care. These were functional flexibility, vertical substitution of staff, meeting externally established performance indicators and outsourcing. We conclude that cost containment alongside of the meeting of performance indicators has extended work traditionally performed during business hours beyond those hours when less staffing and material resources are available. This adds to nursing workload and potentially contributes to incomplete nursing care.

Rounding, work intensification and new public management.

In this study, we argue that contemporary nursing care has been overtaken by new public management strategies aimed at curtailing budgets in the public hospital sector in Australia. Drawing on qualitative interviews with 15 nurses from one public acute hospital with supporting documentary evidence, we demonstrate what happens to nursing work when management imposes rounding as a risk reduction strategy. In the case study outlined rounding was introduced across all wards in response to missed care, which in turn arose as a result of work intensification produced by efficiency, productivity, effectiveness and accountability demands. Rounding is a commercially sponsored practice consistent with new public management. Our study illustrates the impact that new public management strategies such as rounding have on how nurses work, both in terms of work intensity and in who controls their labour.

Quantification of Tumor Burden in a Genetically Engineered Mouse Model of Lung Cancer by Micro-CT and Automated Analysis.

Genetically engineered mouse models (GEMMs) of lung cancer closely recapitulate the human disease but suffer from the difficulty of evaluating tumor growth by conventional methods. Herein, a novel automated image analysis method for estimating the lung tumor burden from in vivo micro-computed tomography (micro-CT) data is described. The proposed tumor burden metric is the segmented soft tissue volume contained within a chest space region of interest, excluding an estimate of the heart volume. The method was validated by comparison with previously published manual analysis methods and applied in two therapeutic studies in a mutant K-ras GEMM of non-small cell lung carcinoma. Mice were imaged by micro-CT pre-treatment and stratified into four treatment groups: an antibody inhibiting vascular endothelial growth factor (anti-VEGF), chemotherapy, combination of anti-VEGF and chemotherapy, or control antibody. In the first study, post-treatment imaging was performed 4 weeks later. In the second study, mice were scanned serially on a high-throughput scanner every 2 weeks for 8 weeks during treatment. In both studies, the automated tumor burden estimates were well correlated with manual metrics (r value range: 0.83-0.93, P < .0001) and showed a similar, significant reduction in tumor growth in mice treated with anti-VEGF alone or in combination with chemotherapy. Given the fully automated nature of this technique, the proposed analysis method can provide a valuable tool in preclinical drug research for screening and randomizing animals into treatment groups and evaluating treatment efficacy in mouse models of lung cancer in a highly robust and efficient manner.

Factors influencing why nursing care is missed.

AIMS AND OBJECTIVES: This study explores the reasons nurses identify missed care and what factors account for this variance in nursing practice. Second, the study seeks to understand if the identified reasons behind missed care interact with one another and form a multidimensional construct. BACKGROUND: This study draws on the results of previous research conducted by Kalisch in developing the MISSCARE research survey tool and now applies it to an Australian context. DESIGN: This study engages a nonexperimental exploratory approach where 16 latent variables are identified and estimated using structural equation modelling to determine the capacity each of these factors has in predicting the reasons for reported missed nursing care. METHODS: Data were obtained from an electronic survey sent to nursing members of the Australian Nursing and Midwifery Federation of South Australia. A self-report, Likert-type instrument was used to capture the strength and direction of consensus derived from a sample of 289 nurses and midwives. RESULTS/FINDINGS: Eight variables were identified as having direct predictor effects as to why nursing care was being missed, and included shift type, nursing resource allocation, health professional communication, workload intensity, workload predictability, the nurses' satisfaction with their current job and their intention to remain working. Additional indirect effects of other variables explained 34% of the variance of the total scores for why nursing care was reported as being missed. CONCLUSION: Historically, the MISSCARE survey has identified and quantified what types of nursing care is missed. This paper takes this concept further by producing an interactional model identifying the effects different variables have on why nursing care is missed. RELEVANCE TO CLINICAL PRACTICE: These Australian findings not only contribute to other international studies that identify why nursing care is omitted, it provides a framework for why reported episodes of missed care can be predicted and subsequently addressed.

Clinical performance of infrared consumer-grade thermometers.

BACKGROUND AND PURPOSE: Technology of ear infrared (IR) thermometers has improved. This study compared a modern ear thermometer to forehead or temporal artery thermometers. METHODS: Temperatures were measured with a heated-tip ear thermometer, a temporal artery thermometer, 3 forehead thermometers, and a thermistor-based reference thermometer in monitor mode. RESULTS: In 171 subjects, mean bias with the forehead thermometers was significantly higher (p < .001) than with the ear thermometer (0.01 degrees C +/- 0.41 degrees C). In 64 febrile subjects, bias with the ear thermometer was significantly lower than with 3 of the other thermometers. A false-negative reading was less likely with the ear thermometer (8%) versus the others (55%, 56%, 28%, and 47%). CONCLUSIONS: Modem ear thermometry provides more precise measurements closer to those of a reference thermometer and is less likely to give false-negative readings than forehead or temporal artery measurements.

SM30 protein function during sea urchin larval spicule formation.

A central issue in better understanding the process of biomineralization is to elucidate the function of occluded matrix proteins present in mineralized tissues. A potent approach to addressing this issue utilizes specific inhibitors of expression of known genes. Application of antisense oligonucleotides that specifically suppress translation of a given mRNA are capable of causing aberrant biomineralization, thereby revealing, at least in part, a likely function of the protein and gene under investigation. We have applied this approach to study the possible function(s) of the SM30 family of proteins, which are found in spicules, teeth, spines, and tests of Strongylocentrotus purpuratus as well as other euechinoid sea urchins. It is possible using the anti-SM30 morpholino-oligonucleotides (MO's) to reduce the level of these proteins to very low levels, yet the development of skeletal spicules in the embryo shows little or no aberration. This surprising result requires re-thinking about the role of these, and possibly other occluded matrix proteins.

Performance of infrared ear and forehead thermometers: a comparative study in 205 febrile and afebrile children.

AIMS AND OBJECTIVES: This study compared readings from two professional-grade, commercially available infrared (IR) thermometers, the ThermoScan® PRO 4000 prewarmed tip ear thermometer and the Temporal Scanner(™) TAT-5000 temporal artery thermometer. BACKGROUND: The repeatability and precision of readings from IR thermometers for professional use were questioned in the past, but in recent years, these types of thermometers have been technologically improved, so their ability to replicate standard temperature readings reliably should be re-examined. DESIGN: Febrile and afebrile children were recruited from the emergency department, overflow treatment areas and the paediatric intensive care unit of a large hospital in Argentina. Each child had a randomised sequence of seven temperature readings, including three from the ear, three from the forehead or behind the ear and one reference oral or rectal reading. METHODS: Temperature readings were taken with the ThermoScan PRO 4000, the Temporal Scanner TAT-5000 and the monitor mode of SureTemp® Plus, a widely used professional-grade contact thermometer, for reference. RESULTS: Of 205 children, 46% were febrile, per reference thermometer readings. While mean ThermoScan PRO 4000 febrile measurements did not differ significantly from reference, mean Temporal Scanner TAT-5000 febrile measurements were significantly lower (by a mean of 0·42 °C) than the reference. Overall bias of the ThermoScan PRO 4000 was significantly lower than that of the Temporal Scanner TAT-5000; repeatability was 1·5 times higher, and overall false-negative rate was about a third that of Temporal Scanner TAT-5000, when compared to the reference. CONCLUSIONS: This study indicates that the ThermoScan PRO 4000 provides measurements closer to those of a professional-grade contact thermometer when compared to the Temporal Scanner TAT-5000. RELEVANCE TO CLINICAL PRACTICE: The odds of misclassifying a febrile child as non-febrile were about threefold higher with the Temporal Scanner TAT-5000 temporal artery thermometer than with the ThermoScan® PRO 4000 ear thermometer.

Anti-VEGF antibody therapy does not promote metastasis in genetically engineered mouse tumour models.

Resistance to anti-angiogenic therapy can occur via several potential mechanisms. Unexpectedly, recent studies showed that short-term inhibition of either VEGF or VEGFR enhanced tumour invasiveness and metastatic spread in preclinical models. In an effort to evaluate the translational relevance of these findings, we examined the consequences of long-term anti-VEGF monoclonal antibody therapy in several well-validated genetically engineered mouse tumour models of either neuroendocrine or epithelial origin. Anti-VEGF therapy decreased tumour burden and increased overall survival, either as a single agent or in combination with chemotherapy, in all four models examined. Importantly, neither short- nor long-term exposure to anti-VEGF therapy altered the incidence of metastasis in any of these autochthonous models, consistent with retrospective analyses of clinical trials. In contrast, we observed that sunitinib treatment recapitulated previously reported effects on tumour invasiveness and metastasis in a pancreatic neuroendocrine tumour (PNET) model. Consistent with these results, sunitinib treatment resulted in an up-regulation of the hypoxia marker GLUT1 in PNETs, whereas anti-VEGF did not. These results indicate that anti-VEGF mediates anti-tumour effects and therapeutic benefits without a paradoxical increase in metastasis. Moreover, these data underscore the concept that drugs targeting VEGF ligands and receptors may affect tumour metastasis in a context-dependent manner and are mechanistically distinct from one another.

A change of direction. Interview by Alison Whyte.

Since last autumn NHS Direct has been recruiting nurses with less experience to take patients' calls. Its deputy chief nurse explains why.

Assessing therapeutic responses in Kras mutant cancers using genetically engineered mouse models.

The low rate of approval of novel anti-cancer agents underscores the need for better preclinical models of therapeutic response as neither xenografts nor early-generation genetically engineered mouse models (GEMMs) reliably predict human clinical outcomes. Whereas recent, sporadic GEMMs emulate many aspects of their human disease counterpart more closely, their ability to predict clinical therapeutic responses has never been tested systematically. We evaluated the utility of two state-of-the-art, mutant Kras-driven GEMMs--one of non-small-cell lung carcinoma and another of pancreatic adenocarcinoma--by assessing responses to existing standard-of-care chemotherapeutics, and subsequently in combination with EGFR and VEGF inhibitors. Standard clinical endpoints were modeled to evaluate efficacy, including overall survival and progression-free survival using noninvasive imaging modalities. Comparisons with corresponding clinical trials indicate that these GEMMs model human responses well, and lay the foundation for the use of validated GEMMs in predicting outcome and interrogating mechanisms of therapeutic response and resistance.

The dynamics of secretion during sea urchin embryonic skeleton formation.

Skeleton formation involves secretion of massive amounts of mineral precursor, usually a calcium salt, and matrix proteins, many of which are deposited on, or even occluded within, the mineral. The cell biological underpinnings of this secretion and subsequent assembly of the biomineralized skeletal element is not well understood. We ask here what is the relationship of the trafficking and secretion of the mineral and matrix within the primary mesenchyme cells of the sea urchin embryo, cells that deposit the endoskeletal spicule. Fluorescent labeling of intracellular calcium deposits show mineral precursors are present in granules visible by light microscopy, from whence they are deposited in the endoskeletal spicule, especially at its tip. In contrast, two different matrix proteins tagged with GFP are present in smaller post-Golgi vesicles only seen by electron microscopy, and the secreted protein are only incorporated into the spicule in the vicinity of the cell of origin. The matrix protein, SpSM30B, is post-translationally modified during secretion, and this processing continues after its incorporation into the spicule. Our findings also indicate that the mineral precursor and two well characterized matrix proteins are trafficked by different cellular routes.

Ethical dilemmas in training tomorrow's doctors.

This article describes some of the challenges that face trainers and trainees in medical education. There are ethical issues surrounding the use of real patients - particularly children and young people. How much can a young trainee "practise" on a patient? How can they best learn practical skills or gain experience of intimate examinations? The requirements of professional behaviour of trainers towards trainees and of both towards patients are described. Patients involvement in teaching, assessment and formal examinations is discussed.