ACE research vignette 017: The new venture mortality myth

This series of research vignettes is aimed at sharing current and interesting research findings from our team of internatinal Entrepreneurship researchers. In this vignette, Dr Jonathan Levie of the University of Strathclyde notes wide and persistent gaps between perceptions and measures of new business mortality, and discusses possible implications.

The relationship between firm survival and innovation : an introduction to the literature

The rapid growth in use of the Internet as a business tool provides a new perspective in the study of the organizational challenges of new technologies. The innovation literature has grown vastly since its establishment in the 1920s, covering a broad range of disciplines (Foxall 1984) and measures a wide variety of variables (Rogers 1995). At first glance, studies that look at the relationship between innovation and firm survival appear contradictory. However, the results appear compatible when additional factors, such as industry type, organizational age, company size or the duration of the study are taken into account.

Revision total hip replacement using the cement-in-cement technique for the acetabular component : technique and results for 60 hips

The technique of femoral cement-in-cement revision is well established, but there are no previous series reporting its use on the acetabular side at the time of revision total hip arthroplasty. We describe the surgical technique and report the outcome of 60 consecutive cement-in-cement revisions of the acetabular component at a mean follow-up of 8.5 years (range 5-12 years). All had a radiologically and clinically well fixed acetabular cement mantle at the time of revision. 29 patients died. No case was lost to follow-up. The 2 most common indications for acetabular revision were recurrent dislocation (77%) and to compliment a femoral revision (20%). There were 2 cases of aseptic cup loosening (3.3%) requiring re-revision. No other hip was clinically or radiologically loose (96.7%) at latest follow-up. One case was re-revised for infection, 4 for recurrent dislocation and 1 for disarticulation of a constrained component. At 5 years, the Kaplan-Meier survival rate was 100% for aseptic loosening and 92.2% (95% CI; 84.8-99.6%) with revision for all causes as the endpoint. These results support the use of the cement-in-cement revision technique in appropriate cases on the acetabular side. Theoretical advantages include preservation of bone stock, reduced operating time, reduced risk of complications and durable fixation.

The impact of malnutrition and decreased food intake on length of stay, readmission, and mortality in acute care patients

Rationale: The Australasian Nutrition Care Day Survey (ANCDS) evaluated if malnutrition and decreased food intake are independent risk factors for negative outcomes in hospitalised patients. Methods: A multicentre (56 hospitals) cross-sectional survey was conducted in two phases. Phase 1 evaluated nutritional status (defined by Subjective Global Assessment) and 24-hour food intake recorded as 0, 25, 50, 75, and 100% intake. Phase 2 data, which included length of stay (LOS), readmissions and mortality, were collected 90 days post-Phase 1. Logistic regression was used to control for confounders: age, gender, disease type and severity (using Patient Clinical Complexity Level scores). Results: Of 3122 participants (53% males, mean age: 65±18 years) 32% were malnourished and 23% consumed�25% of the offered food. Median LOS for malnourished (MN) patients was higher than well-nourished (WN) patients (15 vs. 10 days, p<0.0001). Median LOS for patients consuming �25% of the food was higher than those consuming �50% (13 vs. 11 days, p<0.0001). MN patients had higher readmission rates (36% vs. 30%, p = 0.001). The odds ratios of 90-day in-hospital mortality were 1.8 times greater for MN patients (CI: 1.03 3.22, p = 0.04) and 2.7 times greater for those consuming �25% of the offered food (CI: 1.54 4.68, p = 0.001). Conclusion: The ANCDS demonstrates that malnutrition and/or decreased food intake are associated with longer LOS and readmissions. The survey also establishes that malnutrition and decreased food intake are independent risk factors for in-hospital mortality in acute care patients; and highlights the need for appropriate nutritional screening and support during hospitalisation. Disclosure of Interest: None Declared.

Recruitment and results of a pilot trial of vitamin D supplementation in the general population of Australia

Context: The benefits of high serum levels of 25-hydroxyvitamin D [25(OH)D] are unclear. Trials are needed to establish an appropriate evidence base. Objective: We plan to conduct a large-scale trial of vitamin D supplementation for the reduction of cancer incidence and overall mortality and report here the methods and results of a pilot trial established to inform its design. Design: Pilot D-Health was a randomized trial carried out in a general community setting with 12 months intervention and follow-up. Participants: Participants were 60- to 84-yr-old residents of one of the four eastern Australian states who did not have any vitamin D-related disorders and who were not taking more than 400 IU supplementary vitamin D per day. A total of 644 participants were randomized, and 615 completed the study (two persons withdrew because of nonserious adverse events). Interventions: The interventions were monthly doses of placebo or 30,000 or 60,000 IU vitamin D3. Main Outcomes: The main outcomes were the recruitment rate and changes in serum 25(OH)D. Results: Ten percent of those approached were recruited. At baseline, the mean 25(OH)D was 42 nmol/liter in all three study arms. The mean change in 25(OH)D in the placebo group was 0.12 nmol/liter, compared with changes of 22 and 36 nmol/liter in the 30,000- and 60,000-IU groups, respectively. Conclusions: The D-Health pilot has shown that a large trial is feasible in Australia and that a dose of 2000 IU/d will be needed to ensure that a large proportion of the population reaches the target serum 25(OH)D level. Copyright © 2012 by The Endocrine Society.

Socioeconomic inequalities in cardiovascular mortality and the role of childhood socioeconomic conditions and adulthood risk factors : a prospective cohort study with 17-years of follow up

Background The mechanisms underlying socioeconomic inequalities in mortality from cardiovascular diseases (CVD) are largely unknown. We studied the contribution of childhood socioeconomic conditions and adulthood risk factors to inequalities in CVD mortality in adulthood. Methods The prospective GLOBE study was carried out in the Netherlands, with baseline data from 1991, and linked with the cause of death register in 2007. At baseline, participants reported on adulthood socioeconomic position (SEP) (own educational level), childhood socioeconomic conditions (occupational level of respondent’s father), and a broad range of adulthood risk factors (health behaviours, material circumstances, psychosocial factors). This present study is based on 5,395 men and 6,306 women, and the data were analysed using Cox regression models and hazard ratios (HR). Results A low adulthood SEP was associated with increased CVD mortality for men (HR 1.84; 95% CI: 1.41-2.39) and women (HR 1.80; 95%CI: 1.04-3.10). Those with poorer childhood socioeconomic conditions were more likely to die from CVD in adulthood, but this reached statistical significance only among men with the poorest childhood socioeconomic circumstances. About half of the investigated adulthood risk factors showed significant associations with CVD mortality among both men and women, namely renting a house, experiencing financial problems, smoking, physical activity and marital status. Alcohol consumption and BMI showed a U-shaped relationship with CVD mortality among women, with the risk being significantly greater for both abstainers and heavy drinkers, and among women who were underweight or obese. Among men, being single or divorced and using sleep/anxiety drugs increased the risk of CVD mortality. In explanatory models, the largest contributor to adulthood CVD inequalities were material conditions for men (42%; 95% CI: −73 to −20) and behavioural factors for women (55%; 95% CI: -191 to −28). Simultaneous adjustment for adulthood risk factors and childhood socioeconomic conditions attenuated the HR for the lowest adulthood SEP to 1.34 (95% CI: 0.99-1.82) for men and 1.19 (95% CI: 0.65-2.15) for women. Conclusions Adulthood material, behavioural and psychosocial factors played a major role in the explanation of adulthood SEP inequalities in CVD mortality. Childhood socioeconomic circumstances made a modest contribution, mainly via their association with adulthood risk factors. Policies and interventions to reduce health inequalities are likely to be most effective when considering the influence of socioeconomic circumstances across the entire life course and in particular, poor material conditions and unhealthy behaviours in adulthood.

Nurse staffing levels and the incidence of mortality and morbidity in the adult intensive care unit : a literature review

BACKGROUND: Studies have shown that nurse staffing levels, among many other factors in the hospital setting, contribute to adverse patient outcomes. Concerns about patient safety and quality of care have resulted in numerous studies being conducted to examine the relationship between nurse staffing levels and the incidence of adverse patient events in both general wards and intensive care units. AIM: The aim of this paper is to review literature published in the previous 10 years which examines the relationship between nurse staffing levels and the incidence of mortality and morbidity in adult intensive care unit patients. METHODS: A literature search from 2002 to 2011 using the MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and Australian digital thesis databases was undertaken. The keywords used were: intensive care; critical care; staffing; nurse staffing; understaffing; nurse-patient ratios; adverse outcomes; mortality; ventilator-associated pneumonia; ventilator-acquired pneumonia; infection; length of stay; pressure ulcer/injury; unplanned extubation; medication error; readmission; myocardial infarction; and renal failure. A total of 19 articles were included in the review. Outcomes of interest are patient mortality and morbidity, particularly infection and pressure ulcers. RESULTS: Most of the studies were observational in nature with variables obtained retrospectively from large hospital databases. Nurse staffing measures and patient outcomes varied widely across the studies. While an overall statistical association between increased nurse staffing levels and decreased adverse patient outcomes was not found in this review, most studies concluded that a trend exists between increased nurse staffing levels and decreased adverse events. CONCLUSION: While an overall statistical association between increased nurse staffing levels and decreased adverse patient outcomes was not found in this review, most studies demonstrated a trend between increased nurse staffing levels and decreased adverse patient outcomes in the intensive care unit which is consistent with previous literature. While further more robust research methodologies need to be tested in order to more confidently demonstrate this association and decrease the influence of the many other confounders to patient outcomes; this would be difficult to achieve in this field of research.

Survival, sublethal injury and recovery of environmental Burkholderia pseudomallei in soil subjected to desiccation

Environmental Burkholderia pseudomallei isolated from sandy soil at Castle Hill, Townsville, in the dry tropic region of Queensland, Australia, was inoculated into sterile-soil laboratory microcosms subjected to variable soil moisture. Survival and sublethal injury of the B. pseudomallei strain were monitored by recovery using culture-based methods. Soil extraction buffer yielded higher recoveries as an extraction agent than sterile distilled water. B. pseudomallei was not recoverable when inoculated into desiccated soil but remained recoverable from moist soil subjected to 91 days desiccation and showed a growth response to increased soil moisture over at least 113 days. Results indicate that endemic dry tropic soil may act as a reservoir during the dry season, with an increase in cell number and potential for mobilization from soil into water in the wet season.

The results of acetabular impaction grafting in 129 primary cemented total hip arthroplasties

Between 1995 and 2003, 129 cemented primary THRs were performed using full acetabular impaction grafting to reconstruct acetabular deficiencies. These were classified as cavitary in 74 and segmental in 55 hips. Eighty-one patients were reviewed at mean 9.1 (6.2-14.3) years post-operatively. There were seven acetabular component revisions due to aseptic loosening, and a further 11 cases that had migrated >5mm or tilted >5° on radiological review - ten of which reported no symptoms. Kaplan-Meier analysis of revisions for aseptic loosening demonstrates 100% survival at nine years for cavitary defects compared to 82.6% for segmental defects. Our results suggest that the medium-term survival of this technique is excellent when used for purely cavitary defects but less predictable when used with large rim meshes in segmental defects.

Estimating the effects of ambient temperature on mortality : methodological challenges and proposed solutions

The health impacts of exposure to ambient temperature have been drawing increasing attention from the environmental health research community, government, society, industries, and the public. Case-crossover and time series models are most commonly used to examine the effects of ambient temperature on mortality. However, some key methodological issues remain to be addressed. For example, few studies have used spatiotemporal models to assess the effects of spatial temperatures on mortality. Few studies have used a case-crossover design to examine the delayed (distributed lag) and non-linear relationship between temperature and mortality. Also, little evidence is available on the effects of temperature changes on mortality, and on differences in heat-related mortality over time. This thesis aimed to address the following research questions: 1. How to combine case-crossover design and distributed lag non-linear models? 2. Is there any significant difference in effect estimates between time series and spatiotemporal models? 3. How to assess the effects of temperature changes between neighbouring days on mortality? 4. Is there any change in temperature effects on mortality over time? To combine the case-crossover design and distributed lag non-linear model, datasets including deaths, and weather conditions (minimum temperature, mean temperature, maximum temperature, and relative humidity), and air pollution were acquired from Tianjin China, for the years 2005 to 2007. I demonstrated how to combine the case-crossover design with a distributed lag non-linear model. This allows the case-crossover design to estimate the non-linear and delayed effects of temperature whilst controlling for seasonality. There was consistent U-shaped relationship between temperature and mortality. Cold effects were delayed by 3 days, and persisted for 10 days. Hot effects were acute and lasted for three days, and were followed by mortality displacement for non-accidental, cardiopulmonary, and cardiovascular deaths. Mean temperature was a better predictor of mortality (based on model fit) than maximum or minimum temperature. It is still unclear whether spatiotemporal models using spatial temperature exposure produce better estimates of mortality risk compared with time series models that use a single site’s temperature or averaged temperature from a network of sites. Daily mortality data were obtained from 163 locations across Brisbane city, Australia from 2000 to 2004. Ordinary kriging was used to interpolate spatial temperatures across the city based on 19 monitoring sites. A spatiotemporal model was used to examine the impact of spatial temperature on mortality. A time series model was used to assess the effects of single site’s temperature, and averaged temperature from 3 monitoring sites on mortality. Squared Pearson scaled residuals were used to check the model fit. The results of this study show that even though spatiotemporal models gave a better model fit than time series models, spatiotemporal and time series models gave similar effect estimates. Time series analyses using temperature recorded from a single monitoring site or average temperature of multiple sites were equally good at estimating the association between temperature and mortality as compared with a spatiotemporal model. A time series Poisson regression model was used to estimate the association between temperature change and mortality in summer in Brisbane, Australia during 1996–2004 and Los Angeles, United States during 1987–2000. Temperature change was calculated by the current day's mean temperature minus the previous day's mean. In Brisbane, a drop of more than 3 �C in temperature between days was associated with relative risks (RRs) of 1.16 (95% confidence interval (CI): 1.02, 1.31) for non-external mortality (NEM), 1.19 (95% CI: 1.00, 1.41) for NEM in females, and 1.44 (95% CI: 1.10, 1.89) for NEM aged 65.74 years. An increase of more than 3 �C was associated with RRs of 1.35 (95% CI: 1.03, 1.77) for cardiovascular mortality and 1.67 (95% CI: 1.15, 2.43) for people aged < 65 years. In Los Angeles, only a drop of more than 3 �C was significantly associated with RRs of 1.13 (95% CI: 1.05, 1.22) for total NEM, 1.25 (95% CI: 1.13, 1.39) for cardiovascular mortality, and 1.25 (95% CI: 1.14, 1.39) for people aged . 75 years. In both cities, there were joint effects of temperature change and mean temperature on NEM. A change in temperature of more than 3 �C, whether positive or negative, has an adverse impact on mortality even after controlling for mean temperature. I examined the variation in the effects of high temperatures on elderly mortality (age . 75 years) by year, city and region for 83 large US cities between 1987 and 2000. High temperature days were defined as two or more consecutive days with temperatures above the 90th percentile for each city during each warm season (May 1 to September 30). The mortality risk for high temperatures was decomposed into: a "main effect" due to high temperatures using a distributed lag non-linear function, and an "added effect" due to consecutive high temperature days. I pooled yearly effects across regions and overall effects at both regional and national levels. The effects of high temperature (both main and added effects) on elderly mortality varied greatly by year, city and region. The years with higher heat-related mortality were often followed by those with relatively lower mortality. Understanding this variability in the effects of high temperatures is important for the development of heat-warning systems. In conclusion, this thesis makes contribution in several aspects. Case-crossover design was combined with distribute lag non-linear model to assess the effects of temperature on mortality in Tianjin. This makes the case-crossover design flexibly estimate the non-linear and delayed effects of temperature. Both extreme cold and high temperatures increased the risk of mortality in Tianjin. Time series model using single site’s temperature or averaged temperature from some sites can be used to examine the effects of temperature on mortality. Temperature change (no matter significant temperature drop or great temperature increase) increases the risk of mortality. The high temperature effect on mortality is highly variable from year to year.

SECIS-binding protein 2 promotes cell survival by protecting against oxidative stress

Reactive oxygen species (ROS) are a primary cause of cellular damage that leads to cell death. In cells, protection from ROS-induced damage and maintenance of the redox balance is mediated to a large extent by selenoproteins, a distinct family of proteins that contain selenium in form of selenocysteine (Sec) within their active site. Incorporation of Sec requires the Sec-insertion sequence element (SECIS) in the 3'-untranslated region of selenoproteins mRNAs and the SECIS-binding protein 2 (SBP2). Previous studies have shown that SBP2 is required for the Sec-incorporation mechanism; however, additional roles of SBP2 in the cell have remained undefined. We herein show that depletion of SBP2 by using antisense oligonucleotides (ASOs) causes oxidative stress and induction of caspase- and cytochrome c-dependent apoptosis. Cells depleted of SBP2 have increased levels of ROS, which lead to cellular stress manifested as 8-oxo-7,8-dihydroguanine (8-oxo-dG) DNA lesions, stress granules, and lipid peroxidation. Small-molecule antioxidants N-acetylcysteine, glutathione, and α-tocopherol only marginally reduced ROS and were unable to rescue cells fully from apoptosis, indicating that apoptosis might be directly mediated by selenoproteins. Our results demonstrate that SBP2 is required for protection against ROS-induced cellular damage and cell survival. Antioxid. Redox Signal. 12, 797–808.

Extremely cold and hot temperatures increase the risk of ischaemic heart disease mortality : epidemiological evidence from China

Objective: To examine the effects of extremely cold and hot temperatures on ischaemic heart disease (IHD) mortality in five cities (Beijing, Tianjin, Shanghai, Wuhan and Guangzhou) in China; and to examine the time relationships between cold and hot temperatures and IHD mortality for each city. Design: A negative binomial regression model combined with a distributed lag non-linear model was used to examine city-specific temperature effects on IHD mortality up to 20 lag days. A meta-analysis was used to pool the cold effects and hot effects across the five cities. Patients: 16 559 IHD deaths were monitored by a sentinel surveillance system in five cities during 2004–2008. Results: The relationships between temperature and IHD mortality were non-linear in all five cities. The minimum-mortality temperatures in northern cities were lower than in southern cities. In Beijing, Tianjin and Guangzhou, the effects of extremely cold temperatures were delayed, while Shanghai and Wuhan had immediate cold effects. The effects of extremely hot temperatures appeared immediately in all the cities except Wuhan. Meta-analysis showed that IHD mortality increased 48% at the 1st percentile of temperature (extremely cold temperature) compared with the 10th percentile, while IHD mortality increased 18% at the 99th percentile of temperature (extremely hot temperature) compared with the 90th percentile. Conclusions: Results indicate that both extremely cold and hot temperatures increase IHD mortality in China. Each city has its characteristics of heat effects on IHD mortality. The policy for response to climate change should consider local climate–IHD mortality relationships.

Effects of soluble dietary cellulose on specific growth rate, survival and digestive enzyme activities in three freshwater crayfish (Cherax) species

Three native freshwater crayfish Cherax species are farmed in Australia namely; Redclaw (Cherax quadricarinatus), Marron (C. tenuimanus), and Yabby (C. destructor). Lack of appropriate data on specific nutrient requirements for each of these species, however, has constrained development of specific formulated diets and hence current use of over-formulated feeds or expensive marine shrimp feeds, limit their profitability. A number of studies have investigated nutritional requirements in redclaw that have focused on replacing expensive fish meal in formulated feeds with non-protein, less expensive substitutes including plant based ingredients. Confirmation that freshwater crayfish possess endogenous cellulase genes, suggests their potential ability to utilize complex carbohydrates like cellulose as nutrient sources in their diet. To date, studies have been limited to only C. quadricarinatus and C. destructor and no studies have compared the relative ability of each species to utilize soluble cellulose in their diets. Individual feeding trials of late-juveniles of each species were conducted separately in an automated recirculating culture system over 12 week cycles. Animals were fed either a test diet (TD) that contained 20% soluble cellulose or a reference diet (RD) substituted with the same amount of corn starch. Water temperature, conductivity and pH were maintained at constant and optimum levels for each species. Animals were fed at 3% of their body weight twice daily and wet body weight was recorded bi-weekly. At the end of experiment, all animals were harvested, measured and midgut gland extracts assayed for alpha-amylase, total protease and cellulase activity levels. After the trial period, redclaw fed with RD showed significantly higher (p<0.05) specific growth rate (SGR) compare with animals fed the TD while SGR of marron and yabby fed the two diets were not significantly different (p<0.05). Cellulase expression levels in redclaw were not significantly different between diets. Marron and yabby showed significantly higher cellulase activity when fed the RD. Amylase and protease activity in all three species were significantly higher in the animals fed with RD (Table 1). These results indicate that test animals of all species can utilize starch better than dietary soluble cellulose in their diet and inclusion of 20% soluble cellulose in diets does not appear to have any significant negative effect on their growth rate but survival was impacted in C. quadricarinatus while not in C. tenuimanus or C. destructor.

Effects of soluble dietary cellulose on specific growth rate, survival and digestive enzyme activities in three freshwater crayfish (Cherax) species

The current study evaluated the effect of soluble dietary cellulose on growth, survival and digestive enzyme activity in three endemic, Australian freshwater crayfish species (redclaw: Cherax quadricarinatus, marron: C. tenuimanus, yabby: C. destructor). Separate individual feeding trials were conducted for late-stage juveniles from each species in an automated recirculating freshwater, culture system. Animals were fed either a test diet (TD) that contained 20% soluble cellulose or a reference diet (RD) substituted with the same amount of corn starch, over a 12 week period. Redclaw fed with RD showed significantly higher (p<0.05) specific growth rates (SGR) compared with animals fed the TD, while SGR of marron and yabby fed the two diets were not significantly different. Expressed cellulase activity levels in redclaw were not significantly different between diets. Marron and yabby showed significantly higher cellulase activity when fed the RD (p<0.05). Amylase and protease activity in all three species were significantly higher in the animals fed with RD (p<0.05). These results indicate that test animals of all three species appear to utilize starch more efficiently than soluble dietary cellulose in their diet. The inclusion of 20% soluble cellulose in diets did not appear, however, to have a significant negative effect on growth rates.