Lessons learnt : complementing good clinical renal questions with an appropriate research strategy

The purpose of this article is to present lessons learnt by nurses when conducting research to encourage colleagues to ask good clinical research questions. This is accomplished by presenting a study designed to challenge current practice which included research flaws. The longstanding practice of weighing renal patients at 0600 hours and then again prior to receiving haemodialysis was examined. Nurses believed that performing the assessment twice, often within a few hours, was unnecessary and that patients were angry when woken to be weighed. An observational study with convenience sampling collected data from 46 individuals requiring haemodialysis, who were repeatedly sampled to provide 139 episodes of data. Although the research hypotheses were rejected, invaluable experience was gained, with research and clinical practice lessons learnt, along with surprising findings.

Gap analysis of intrusion detection in smart grids

Given the recent emergence of the smart grid and smart grid related technologies, their security is a prime concern. Intrusion detection provides a second line of defense. However, conventional intrusion detection systems (IDSs) are unable to adequately address the unique requirements of the smart grid. This paper presents a gap analysis of contemporary IDSs from a smart grid perspective. This paper highlights the lack of adequate intrusion detection within the smart grid and discusses the limitations of current IDSs approaches. The gap analysis identifies current IDSs as being unsuited to smart grid application without significant changes to address smart grid specific requirements.

Ovarian steroid hormones: effects on immune responses and Chlamydia trachomatis infections of the female genital tract

Female sex hormones are known to regulate the adaptive and innate immune functions of the female reproductive tract. This review aims to update our current knowledge of the effects of the sex hormones estradiol and progesterone in the female reproductive tract on innate immunity, antigen presentation, specific immune responses, antibody secretion, genital tract infections caused by Chlamydia trachomatis, and vaccine-induced immunity.

Natural convection in attic-shaped spaces subject to sudden and ramp heating boundary conditions

In this study, a discussion of the fluid dynamics in the attic space is reported, focusing on its transient response to sudden and linear changes of temperature along the two inclined walls. The transient behaviour of an attic space is relevant to our daily life. The instantaneous and non-instantaneous (ramp) heating boundary condition is applied on the sloping walls of the attic space. A theoretical understanding of the transient behaviour of the flow in the enclosure is performed through scaling analysis. A proper identification of the timescales, the velocity and the thickness relevant to the flow that develops inside the cavity makes it possible to predict theoretically the basic flow features that will survive once the thermal flow in the enclosure reaches a steady state. A time scale for the heating-up of the whole cavity together with the heat transfer scales through the inclined walls has also been obtained through scaling analysis. All scales are verified by the numerical simulations.

Intrinsically photosensitive melanopsin retinal ganglion cell contributions to the post-illumination pupil response and circadian rhythm

Intrinsically photosensitive retinal ganglion cells (ipRGCs) in the eye transmit the environmental light level, projecting to the suprachiasmatic nucleus (SCN) (Berson, Dunn & Takao, 2002; Hattar, Liao, Takao, Berson & Yau, 2002), the location of the circadian biological clock, and the olivary pretectal nucleus (OPN) of the pretectum, the start of the pupil reflex pathway (Hattar, Liao, Takao, Berson & Yau, 2002; Dacey, Liao, Peterson, Robinson, Smith, Pokorny, Yau & Gamlin, 2005). The SCN synchronizes the circadian rhythm, a cycle of biological processes coordinated to the solar day, and drives the sleep/wake cycle by controlling the release of melatonin from the pineal gland (Claustrat, Brun & Chazot, 2005). Encoded photic input from ipRGCs to the OPN also contributes to the pupil light reflex (PLR), the constriction and recovery of the pupil in response to light. IpRGCs control the post-illumination component of the PLR, the partial pupil constriction maintained for > 30 sec after a stimulus offset (Gamlin, McDougal, Pokorny, Smith, Yau & Dacey, 2007; Kankipati, Girkin & Gamlin, 2010; Markwell, Feigl & Zele, 2010). It is unknown if intrinsic ipRGC and cone-mediated inputs to ipRGCs show circadian variation in their photon-counting activity under constant illumination. If ipRGCs demonstrate circadian variation of the pupil response under constant illumination in vivo, when in vitro ipRGC activity does not (Weng, Wong & Berson, 2009), this would support central control of the ipRGC circadian activity. A preliminary experiment was conducted to determine the spectral sensitivity of the ipRGC post-illumination pupil response under the experimental conditions, confirming the successful isolation of the ipRGC response (Gamlin, et al., 2007) for the circadian experiment. In this main experiment, we demonstrate that ipRGC photon-counting activity has a circadian rhythm under constant experimental conditions, while direct rod and cone contributions to the PLR do not. Intrinsic ipRGC contributions to the post-illumination pupil response decreased 2:46 h prior to melatonin onset for our group model, with the peak ipRGC attenuation occurring 1:25 h after melatonin onset. Our results suggest a centrally controlled evening decrease in ipRGC activity, independent of environmental light, which is temporally synchronized (demonstrates a temporal phase-advanced relationship) to the SCN mediated release of melatonin. In the future the ipRGC post-illumination pupil response could be developed as a fast, non-invasive measure of circadian rhythm. This study establishes a basis for future investigation of cortical feedback mechanisms that modulate ipRGC activity.

Malnutrition and clinical outcomes in elderly patients from a Singapore acute hospital

Older adults, especially those acutely ill, are vulnerable to developing malnutrition due to a range of risk factors. The high prevalence and extensive consequences of malnutrition in hospitalised older adults have been reported extensively. However, there are few well-designed longitudinal studies that report the independent relationship between malnutrition and clinical outcomes after adjustment for a wide range of covariates. Acutely ill older adults are exceptionally prone to nutritional decline during hospitalisation, but few reports have studied this change and impact on clinical outcomes. In the rapidly ageing Singapore population, all this evidence is lacking, and the characteristics associated with the risk of malnutrition are also not well-documented. Despite the evidence on malnutrition prevalence, it is often under-recognised and under-treated. It is therefore crucial that validated nutrition screening and assessment tools are used for early identification of malnutrition. Although many nutrition screening and assessment tools are available, there is no universally accepted method for defining malnutrition risk and nutritional status. Most existing tools have been validated amongst Caucasians using various approaches, but they are rarely reported in the Asian elderly and none has been validated in Singapore. Due to the multiethnicity, cultural, and language differences in Singapore older adults, the results from non-Asian validation studies may not be applicable. Therefore it is important to identify validated population and setting specific nutrition screening and assessment methods to accurately detect and diagnose malnutrition in Singapore. The aims of this study are therefore to: i) characterise hospitalised elderly in a Singapore acute hospital; ii) describe the extent and impact of admission malnutrition; iii) identify and evaluate suitable methods for nutritional screening and assessment; and iv) examine changes in nutritional status during admission and their impact on clinical outcomes. A total of 281 participants, with a mean (+SD) age of 81.3 (+7.6) years, were recruited from three geriatric wards in Tan Tock Seng Hospital over a period of eight months. They were predominantly Chinese (83%) and community-dwellers (97%). They were screened within 72 hours of admission by a single dietetic technician using four nutrition screening tools [Tan Tock Seng Hospital Nutrition Screening Tool (TTSH NST), Nutritional Risk Screening 2002 (NRS 2002), Mini Nutritional Assessment-Short Form (MNA-SF), and Short Nutritional Assessment Questionnaire (SNAQ©)] that were administered in no particular order. The total scores were not computed during the screening process so that the dietetic technician was blinded to the results of all the tools. Nutritional status was assessed by a single dietitian, who was blinded to the screening results, using four malnutrition assessment methods [Subjective Global Assessment (SGA), Mini Nutritional Assessment (MNA), body mass index (BMI), and corrected arm muscle area (CAMA)]. The SGA rating was completed prior to computation of the total MNA score to minimise bias. Participants were reassessed for weight, arm anthropometry (mid-arm circumference, triceps skinfold thickness), and SGA rating at discharge from the ward. The nutritional assessment tools and indices were validated against clinical outcomes (length of stay (LOS) >11days, discharge to higher level care, 3-month readmission, 6-month mortality, and 6-month Modified Barthel Index) using multivariate logistic regression. The covariates included age, gender, race, dementia (defined using DSM IV criteria), depression (defined using a single question “Do you often feel sad or depressed?”), severity of illness (defined using a modified version of the Severity of Illness Index), comorbidities (defined using Charlson Comorbidity Index, number of prescribed drugs and admission functional status (measured using Modified Barthel Index; MBI). The nutrition screening tools were validated against the SGA, which was found to be the most appropriate nutritional assessment tool from this study (refer section 5.6) Prevalence of malnutrition on admission was 35% (defined by SGA), and it was significantly associated with characteristics such as swallowing impairment (malnourished vs well-nourished: 20% vs 5%), poor appetite (77% vs 24%), dementia (44% vs 28%), depression (34% vs 22%), and poor functional status (MBI 48.3+29.8 vs 65.1+25.4). The SGA had the highest completion rate (100%) and was predictive of the highest number of clinical outcomes: LOS >11days (OR 2.11, 95% CI [1.17- 3.83]), 3-month readmission (OR 1.90, 95% CI [1.05-3.42]) and 6-month mortality (OR 3.04, 95% CI [1.28-7.18]), independent of a comprehensive range of covariates including functional status, disease severity and cognitive function. SGA is therefore the most appropriate nutritional assessment tool for defining malnutrition. The TTSH NST was identified as the most suitable nutritional screening tool with the best diagnostic performance against the SGA (AUC 0.865, sensitivity 84%, specificity 79%). Overall, 44% of participants experienced weight loss during hospitalisation, and 27% had weight loss >1% per week over median LOS 9 days (range 2-50). Wellnourished (45%) and malnourished (43%) participants were equally prone to experiencing decline in nutritional status (defined by weight loss >1% per week). Those with reduced nutritional status were more likely to be discharged to higher level care (adjusted OR 2.46, 95% CI [1.27-4.70]). This study is the first to characterise malnourished hospitalised older adults in Singapore. It is also one of the very few studies to (a) evaluate the association of admission malnutrition with clinical outcomes in a multivariate model; (b) determine the change in their nutritional status during admission; and (c) evaluate the validity of nutritional screening and assessment tools amongst hospitalised older adults in an Asian population. Results clearly highlight that admission malnutrition and deterioration in nutritional status are prevalent and are associated with adverse clinical outcomes in hospitalised older adults. With older adults being vulnerable to risks and consequences of malnutrition, it is important that they are systematically screened so timely and appropriate intervention can be provided. The findings highlighted in this thesis provide an evidence base for, and confirm the validity of the current nutrition screening and assessment tools used among hospitalised older adults in Singapore. As the older adults may have developed malnutrition prior to hospital admission, or experienced clinically significant weight loss of >1% per week of hospitalisation, screening of the elderly should be initiated in the community and continuous nutritional monitoring should extend beyond hospitalisation.

Association between infant feeding patterns and diarrhoeal and respiratory illness: a cohort study in Chittagong, Bangladesh

Background In developing countries, infectious diseases such as diarrhoea and acute respiratory infections are the main cause of mortality and morbidity in infants aged less than one year. The importance of exclusive breastfeeding in the prevention of infectious diseases during infancy is well known. Although breastfeeding is almost universal in Bangladesh, the rates of exclusive breastfeeding remain low. This cohort study was designed to compare the prevalence of diarrhoea and acute respiratory infection (ARI) in infants according to their breastfeeding status in a prospective cohort of infants from birth to six months of age. Methods A total of 351 pregnant women were recruited in the Anowara subdistrict of Chittagong. Breastfeeding practices and the 7-day prevalence of diarrhoea and ARI were recorded at monthly home visits. Prevalences were compared using chi-squared tests and logistic regression. Results A total of 272 mother-infant pairs completed the study to six months. Infants who were exclusively breastfed for six months had a significantly lower 7-day prevalence of diarrhoea [AOR for lack of EBF = 2.50 (95%CI 1.10, 5.69), p = 0.03] and a significantly lower 7-day prevalence of ARI [AOR for lack of EBF = 2.31 (95%CI 1.33, 4.00), p < 0.01] than infants who were not exclusively breastfed. However, when the association between patterns of infant feeding (exclusive, predominant and partial breastfeeding) and illness was investigated in more detail, there was no significant difference in the prevalence of diarrhoea between exclusively [6.6% (95% CI 2.8, 10.4)] and predominantly breastfed infants [3.7% (95% CI 0.09, 18.3), (p = 0.56)]. Partially breastfed infants had a higher prevalence of diarrhoea than the others [19.2% (95% CI 10.4, 27.9), (p = 0.01)]. Similarly, although there was a large difference in prevalence in acute respiratory illness between exclusively [54.2% (95%CI 46.6, 61.8)] and predominantly breastfed infants [70.4% (95%CI 53.2, 87.6)] there was no significant difference in the prevalence (p = 0.17). Conclusion The findings suggest that exclusive or predominant breastfeeding can reduce rates of morbidity significantly in this region of rural Bangladesh.

Correlates of Pedometer Use: Results from a Community-based Physical Activity Intervention Trial (10,000 Steps Rockhampton)

Background Pedometers have become common place in physical activity promotion, yet little information exists on who is using them. The multi-strategy, community-based 10,000 Steps Rockhampton physical activity intervention trial provided an opportunity to examine correlates of pedometer use at the population level. Methods Pedometer use was promoted across all intervention strategies including: local media, pedometer loan schemes through general practice, other health professionals and libraries, direct mail posted to dog owners, walking trail signage, and workplace competitions. Data on pedometer use were collected during the 2-year follow-up telephone interviews from random population samples in Rockhampton, Australia, and a matched comparison community (Mackay). Logistic regression analyses were used to determine the independent influence of interpersonal characteristics and program exposure variables on pedometer use. Results Data from 2478 participants indicated that 18.1% of Rockhampton and 5.6% of Mackay participants used a pedometer in the previous 18-months. Rockhampton pedometer users (n = 222) were more likely to be female (OR = 1.59, 95% CI: 1.11, 2.23), aged 45 or older (OR = 1.69, 95% CI: 1.16, 2.46) and to have higher levels of education (university degree OR = 4.23, 95% CI: 1.86, 9.6). Respondents with a BMI > 30 were more likely to report using a pedometer (OR = 1.68, 95% CI: 1.11, 2.54) than those in the healthy weight range. Compared with those in full-time paid work, respondents in 'home duties' were significantly less likely to report pedometer use (OR = 0.18, 95% CI: 0.06, 0.53). Exposure to individual program components, in particular seeing 10,000 Steps street signage and walking trails or visiting the website, was also significantly associated with greater pedometer use. Conclusion Pedometer use varies between population subgroups, and alternate strategies need to be investigated to engage men, people with lower levels of education and those in full-time 'home duties', when using pedometers in community-based physical activity promotion initiatives.

Dynamic axial ligand-site exchange in facially discriminated ruthenium(II) carbonyl and rhodium(III) halide metalloporphyrins

For a series of six-coordinate Ru(II)(CO)L or Rh(III)(X–)L porphyrins which are facially differentiated by having a naphthoquinol- or hydroquinol-containing strap across one face, we show that ligand migration from one face to the other can occur under mild conditions, and that ligand site preference is dependent on the nature of L and X–. For bulky nitrogen-based ligands, the strap can be displaced sideways to accommodate the ligand on the same side as the strap. For the ligand pyrazine, we show 1 H NMR evidence for monodentate and bidentate binding modes on both faces, dependent on ligand concentration and metalloporphyrin structure, and that inter-facial migration is rapid under normal conditions. For monodentate substituted pyridine ligands there is a site dependence on structure, and we show clear evidence of dynamic ligand migration through a series of ligand exchange reactions.

FGFR2 mutations are rare across histologic subtypes of ovarian cancer

OBJECTIVE: Ovarian cancer is the leading cause of death from gynecologic malignancies in the Western world. Fibroblast growth factor receptor (FGFR) signaling has been implicated to play a role in ovarian tumorigenesis. Mutational activation of one member of this receptor family, FGFR2, is a frequent event in endometrioid endometrial cancer. Given the similarities in the histologic and molecular genetics of ovarian and endometrial cancers, we hypothesized that activating FGFR2 mutations may occur in a subset of endometrioid ovarian tumors, and possibly other histotypes. METHODS: Six FGFR2 exons were sequenced in 120 primary ovarian tumors representing the major histologic subtypes. RESULTS: FGFR2 mutation was detected at low frequency in endometrioid (1/46, 2.2%) and serous (1/41, 2.4%) ovarian cancer. No mutations were detected in clear cell, mucinous, or mixed histology tumors or in the ovarian cancer cell lines tested. Functional characterization of the FGFR2 mutations confirmed that the mutations detected in ovarian cancer result in receptor activation. CONCLUSIONS: Despite the low incidence of FGFR2 mutations in ovarian cancer, the two FGFR2 mutations identified in ovarian tumors (S252W, Y376C) overlap with the oncogenic mutations previously identified in endometrial tumors, suggesting activated FGFR2 may contribute to ovarian cancer pathogenesis in a small subset of ovarian tumors.

Bricolage as a path to innovation for resource constrained new firms

Evidence suggests that both start-up and young firms (henceforth: new firms) – despite typically being resource-constrained – are sometimes able to innovate (Katila & Shane 2005). Such firms are seldom able to invest in expensive innovation processes, which suggests that they may rely on other pathways to innovation. In this paper, we test arguments that “bricolage,” defined as making do by applying combinations of the resources at hand to new problems and opportunities, provides a pathway to innovation for new firms. Our results suggest that variations in bricolage behaviors can provide an explanation of innovation under resource constraints by new firms.