Effects of particle size distribution in the response of model granular materials in multi-ring shear

Rail track undergoes complex loading patterns under moving traffic conditions compared to roads due to its continued and discontinued multi-layered structure, including rail, sleepers, ballast layer, sub-ballast layer, and subgrade. Particle size distributions (PSDs) of ballast, subballast, and subgrade layers can be critical in cyclic plastic deformation of rail track under moving traffic on frequent track degradation of rail tracks, especially at bridge transition zones. Conventional test approaches: static shear and cyclic single-point load tests are however unable to replicate actual loading patterns of moving train. Multi-ring shear apparatus; a new type of torsional simple shear apparatus, which can reproduce moving traffic conditions, was used in this study to investigate influence of particle size distribution of rail track layers on cyclic plastic deformation. Three particle size distributions, using glass beads were examined under different loading patterns: cyclic sin-gle-point load, and cyclic moving wheel load to evaluate cyclic plastic deformation of rail track under different loading methods. The results of these tests suggest that particle size distributions of rail track structural layers have significant impacts on cyclic plastic deformation under moving train load. Further, the limitations in con-ventional test methods used in laboratories to estimate the plastic deformation of rail track materials lead to underestimate the plastic deformation of rail tracks.

Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in Type 1 diabetes

OBJECTIVE This study determined if deficits in corneal nerve fiber length (CNFL) assessed using corneal confocal microscopy (CCM) can predict future onset of diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS CNFL and a range of other baseline measures were compared between 90 nonneuropathic patients with type 1 diabetes who did or did not develop DPN after 4 years. The receiver operator characteristic (ROC) curve was used to determine the capability of single and combined measures of neuropathy to predict DPN. RESULTS DPN developed in 16 participants (18%) after 4 years. Factors predictive of 4-year incident DPN were lower CNFL (P = 0.041); longer duration of diabetes (P = 0.002); higher triglycerides (P = 0.023); retinopathy (higher on the Early Treatment of Diabetic Retinopathy Study scale) (P = 0.008); nephropathy (higher albumin-to-creatinine ratio) (P = 0.001); higher neuropathy disability score (P = 0.037); lower cold sensation (P = 0.001) and cold pain (P = 0.027) thresholds; higher warm sensation (P = 0.008), warm pain (P = 0.024), and vibration (P = 0.003) thresholds; impaired monofilament response (P = 0.003); and slower peroneal (P = 0.013) and sural (P = 0.002) nerve conduction velocity. CCM could predict the 4-year incident DPN with 63% sensitivity and 74% specificity for a CNFL threshold cutoff of 14.1 mm/mm2 (area under ROC curve = 0.66, P = 0.041). Combining neuropathy measures did not improve predictive capability. CONCLUSIONS DPN can be predicted by various demographic, metabolic, and conventional neuropathy measures. The ability of CCM to predict DPN broadens the already impressive diagnostic capabilities of this novel ophthalmic marker.

Risk factors associated with corneal nerve alteration in type 1 diabetes in the absence of neuropathy: A longitudinal in vivo corneal confocal microscopy study

Purpose The aim of this study was to determine alterations to the corneal subbasal nerve plexus (SNP) over four years using in vivo corneal confocal microscopy (IVCM) in participants with type 1 diabetes and to identify significant risk factors associated with these alterations. Methods A cohort of 108 individuals with type 1 diabetes and no evidence of peripheral neuropathy at enrollment underwent laser-scanning IVCM, ocular screening, and health and metabolic assessment at baseline and the examinations continued for four subsequent annual visits. At each annual visit, eight central corneal images of the SNP were selected and analyzed to quantify corneal nerve fiber density (CNFD), branch density (CNBD) and fiber length (CNFL). Linear mixed model approaches were fitted to examine the relationship between risk factors and corneal nerve parameters. Results A total of 96 participants completed the final visit and 91 participants completed all visits. No significant relationships were found between corneal nerve parameters and time, sex, duration of diabetes, smoking, alcohol consumption, blood pressure or BMI. However, CNFD was negatively associated with HbA1c (β=-0.76, P<0.01) and age (β=-0.13, P<0.01) and positively related to high density lipids (HDL) (β=2.01, P=0.03). Higher HbA1c (β=-1.58, P=0.04) and age (β=-0.23, P<0.01) also negatively impacted CNBD. CNFL was only affected by higher age (β=-0.06, P<0.01). Conclusions Glycemic control, HDL and age have significant effects on SNP structure. These findings highlight the importance of diabetic management to prevent corneal nerve damage as well as the capability of IVCM for monitoring subclinical alterations in the corneal SNP in diabetes.

Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria

Objective Corneal innervation is increasingly used as a surrogate marker of human diabetic peripheral neuropathy (DPN) however its temporal relationship with the other microvascular complications of diabetes is not fully established. In this cross-sectional, observational study we aimed to assess whether neuropathy occurred in patients with type 1 diabetes, without retinopathy or microalbuminuria. Materials and Methods All participants underwent detailed assessment of peripheral neuropathy [neuropathy disability score (NDS), vibration perception threshold (VPT), peroneal motor nerve conduction velocity (PMNCV), sural sensory nerve conduction velocity (SSNCV) and in vivo corneal confocal microscopy (IVCCM)], retinopathy (digital fundus photography) and albuminuria status [albumin: creatinine ratio (ACR)]. Results 53 patients with Type 1 diabetes with (n=37) and without retinopathy (n=16) were compared to control subjects (n=27). SSNCV, corneal nerve fibre (CNFD) and branch (CNBD) density and length (CNFL) were reduced significantly (p<0.001) in diabetic patients without retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were also significantly (p<0.001) reduced in diabetic patients without microalbuminuria (n=39), compared to control subjects. Greater neuropathic severity was associated with established retinopathy and microalbuminuria. Conclusions IVCCM detects early small fibre damage in the absence of retinopathy or microalbuminuria in patients with Type 1 diabetes.

Lens shape and refractive index distribution in type 1 diabetes

Purpose: To compare lens dimensions and refractive index distributions in type 1 diabetes and age-matched control groups. Methods: There were 17 participants with type 1 diabetes, consisting of two subgroups (7 young [23 ± 4 years] and 10 older [54 ± 4 years] participants), with 23 controls (13 young, 24 ± 4 years; 10 older, 55 ± 4 years). For each participant, one eye was tested with relaxed accommodation. A 3T clinical magnetic resonance imaging scanner was used to image the eye, employing a multiple spin echo (MSE) sequence to determine lens dimensions and refractive index profiles along the equatorial and axial directions. Results: The diabetes group had significantly smaller lens equatorial diameters and larger lens axial thicknesses than the control group (diameter mean ± 95% confidence interval [CI]: diabetes group 8.65 ± 0.26 mm, control group 9.42 ± 0.18 mm; axial thickness: diabetes group 4.33 ± 0.30 mm, control group 3.80 ± 0.14 mm). These differences were also significant within each age group. The older group had significantly greater axial thickness than the young group (older group 4.35 ± 0.26 mm, young group 3.70 ± 0.25 mm). Center refractive indices of diabetes and control groups were not significantly different. There were some statistically significant differences between the refractive index fitting parameters of young and older groups, but not between diabetes and control groups of the same age. Conclusions: Smaller lens diameters occurred in the diabetes groups than in the age-matched control groups. Differences in refractive index distribution between persons with and without diabetes are too small to have important effects on instruments measuring axial thickness.

Identifying advanced practice: A national survey of a nursing workforce

Background The size and flexibility of the nursing workforce has positioned nursing as central to the goals of health service improvement. Nursing's response to meeting these goals has resulted in proliferation of advanced practice nursing with a confusing array of practice profiles, titles and roles. Whilst numerous models and definitions of advanced practice nursing have been developed there is scant published research of significant scope that supports these models. Consequently there is an ongoing call in the literature for clarity and stability in nomenclature, and confusion in the health industry on how to optimise the utility of advanced practice nursing. Objectives To identify and delineate advanced practice from other levels of nursing practice through examination of a national nursing workforce. Design A cross-sectional electronic survey of nurses using the validated Advanced Practice Role Delineation tool based on the Strong Model of Advanced Practice. Participants Study participants were registered nurses employed in a clinical service environment across all states and territories of Australia. Methods A sample of 5662 registered nurses participated in the study. Domain means for each participant were calculated then means for nursing position titles were calculated. Position titles were grouped by delineation and were compared with one-way analysis of variance on domain means. The alpha for all tests was set at 0.05. Significant effects were examined with Scheffe post hoc comparisons to control for Type 1 error. Results The survey tool was able to identify position titles where nurses were practicing at an advanced level and to delineate this cohort from other levels of nursing practice, including nurse practitioner. The results show that nurses who practice at an advanced level are characterised by high mean scores across all Domains of the Strong Model of Advanced Practice. The mean scores of advanced practice nurses were significantly different from nurse practitioners in the Direct Care Domain and significantly different from other levels of nurse across all domains. Conclusions The study results show that the nurse practitioner, advanced practice nurse and foundation level registered nurse have different patterns of practice and the Advanced Practice Role Delineation tool has the capacity to clearly delineate and define advanced practice nursing. These findings make a significant contribution to the international debate and show that the profession can now identify what is and what is not advanced practice in nursing.

Factors influencing hospital readmission and length of stay of Vietnamese patients with type 2 diabetes and cardiac disease

Background: Increased hospital readmission and longer stays in the hospital for patients with type 2 diabetes and cardiac disease can result in higher healthcare costs and heavier individual burden. Thus, knowledge of the characteristics and predictive factors for Vietnamese patients with type 2 diabetes and cardiac disease, at high risk of hospital readmission and longer stays in the hospital, could provide a better understanding on how to develop an effective care plan aimed at improving patient outcomes. However, information about factors influencing hospital readmission and length of stay of patients with type 2 diabetes and cardiac disease in Vietnam is limited. Aim: This study examined factors influencing hospital readmission and length of stay of Vietnamese patients with both type 2 diabetes and cardiac disease. Methods: An exploratory prospective study design was conducted on 209 patients with type 2 diabetes and cardiac disease in Vietnam. Data were collected from patient charts and patients' responses to self-administered questionnaires. Descriptive statistics, bivariate correlation, logistic and multiple regression were used to analyse the data. Results: The hospital readmission rate was 12.0% among patients with both type 2 diabetes and cardiac disease. The average length of stay in the hospital was 9.37 days. Older age (OR= 1.11, p< .05), increased duration of type 2 diabetes (OR= 1.22, p< .05), less engagement in stretching/strengthening exercise behaviours (OR= .93, p< .001) and in communication with physician (OR= .21, p< .001) were significant predictors of 30-dayhospital readmission. Increased number of additional co-morbidities (β= .33, p< .001) was a significant predictor of longer stays in the hospital. High levels of cognitive symptom management (β= .40, p< .001) significantly predicted longer stays in the hospital, indicating that the more patients practiced cognitive symptom management, the longer the stay in hospital. Conclusions: This study provides some evidence of factors influencing hospital readmission and length of stay and argues that this information may have significant implications for clinical practice in order to improve patients' health outcomes. However, the findings of this study related to the targeted hospital only. Additionally, the investigation of environmental factors is recommended for future research as these factors are important components contributing to the research model.

Peripartum management of glycemia in women with type 1 diabetes

OBJECTIVE We aimed to 1) describe the peripartum management of type 1 diabetes at an Australian teaching hospital and 2) discuss factors influencing the apparent transient insulin independence postpartum. RESEARCH DESIGN AND METHODS We conducted a retrospective review of women with type 1 diabetes delivering singleton pregnancies from 2005 to 2010. Information was collected regarding demographics, medical history, peripartum management and outcome, and breast-feeding. To detect a difference in time to first postpartum blood glucose level (BGL) >8 mmol/L between women with an early (<4 h) and late (>12 h) requirement for insulin postpartum, with a power of 80% and a type 1 error of 0.05, at least 24 patients were required. RESULTS An intravenous insulin infusion was commenced in almost 95% of women. Univariate analysis showed that increased BMI at term, lower creatinine at term, longer duration from last dose of long- or intermediate-acting insulin, and discontinuation of an insulin infusion postpartum were associated with a shorter time to first requirement of insulin postpartum (P = 0.005, 0.026, 0.026, and <0.001, respectively). There was a correlation between higher doses of insulin commenced postpartum and number of out-of-range BGLs (r[36] = 0.358, P = 0.030) and hypoglycemia (r[36] = 0.434, P = 0.007). Almost 60% had at least one BGL <3.5 mmol/L between delivery and discharge. CONCLUSIONS Changes in the pharmacodynamic profile of insulin may contribute to the transient insulin independence sometimes observed postpartum in type 1 diabetes. A dose of 50–60% of the prepregnancy insulin requirement resulted in the lowest rate of hypoglycemia and glucose excursions. These results require validation in a larger, prospective study.

The reproducibility of acquiring three dimensional gait and plantar pressure data using established protocols in participants with and without type 2 diabetes and foot ulcers

Background Several prospective studies have suggested that gait and plantar pressure abnormalities secondary to diabetic peripheral neuropathy contributes to foot ulceration. There are many different methods by which gait and plantar pressures are assessed and currently there is no agreed standardised approach. This study aimed to describe the methods and reproducibility of three-dimensional gait and plantar pressure assessments in a small subset of participants using pre-existing protocols. Methods Fourteen participants were conveniently sampled prior to a planned longitudinal study; four patients with diabetes and plantar foot ulcers, five patients with diabetes but no foot ulcers and five healthy controls. The repeatability of measuring key biomechanical data was assessed including the identification of 16 key anatomical landmarks, the measurement of seven leg dimensions, the processing of 22 three-dimensional gait parameters and the analysis of four different plantar pressures measures at 20 foot regions. Results The mean inter-observer differences were within the pre-defined acceptable level (<7 mm) for 100 % (16 of 16) of key anatomical landmarks measured for gait analysis. The intra-observer assessment concordance correlation coefficients were > 0.9 for 100 % (7 of 7) of leg dimensions. The coefficients of variations (CVs) were within the pre-defined acceptable level (<10 %) for 100 % (22 of 22) of gait parameters. The CVs were within the pre-defined acceptable level (<30 %) for 95 % (19 of 20) of the contact area measures, 85 % (17 of 20) of mean plantar pressures, 70 % (14 of 20) of pressure time integrals and 55 % (11 of 20) of maximum sensor plantar pressure measures. Conclusion Overall, the findings of this study suggest that important gait and plantar pressure measurements can be reliably acquired. Nearly all measures contributing to three-dimensional gait parameter assessments were within predefined acceptable limits. Most plantar pressure measurements were also within predefined acceptable limits; however, reproducibility was not as good for assessment of the maximum sensor pressure. To our knowledge, this is the first study to investigate the reproducibility of several biomechanical methods in a heterogeneous cohort.

Glycaemic behaviour during breastfeeding in women with Type 1 diabetes

Aim To describe glycaemia in both breastfeeding women and artificially feeding women with Type 1 diabetes, and the changes in glycaemia induced by suckling. Methods A blinded continuous glucose monitor was applied for up to 6 days in eight breastfeeding and eight artificially feeding women with Type 1 diabetes 2–4 months postpartum. Women recorded glucose levels, insulin dosages, oral intake and breastfeeding episodes. A standardized breakfast was consumed on 2 days. A third group (clinic controls) were identified from a historical database. Results Carbohydrate intake tended to be higher in breastfeeding than artificially feeding women (P = 0.09) despite similar insulin requirements. Compared with breastfeeding women, the high blood glucose index and standard deviation of glucose were higher in artificially feeding women (P = 0.02 and 0.06, respectively) and in the clinical control group (P = 0.02 and 0.05, respectively). The low blood glucose index and hypoglycaemia were similar. After suckling, the low blood glucose index increased compared with before (P < 0.01) and during (P < 0.01) suckling. Hypoglycaemia (blood glucose < 4.0 mmol/l) occurred within 3 h of suckling in 14% of suckling episodes, and was associated with time from last oral intake (P = 0.04) and last rapid-acting insulin (P = 0.03). After a standardized breakfast, the area under the glucose curve was positive. In breastfeeding women the area under the glucose curve was positive if suckling was avoided for 1 h after eating and negative if suckling occurred within 30 min of eating. Conclusions Breastfeeding women with Type 1 diabetes had similar hypoglycaemia but lower glucose variability than artificially feeding women. Suckling reduced maternal glucose levels but did not cause hypoglycaemia in most episodes.

Improving the selectivity of engineered protease inhibitors: Optimizing the P2 prime residue using a versatile cyclic peptide library

Standard mechanism inhibitors are attractive design templates for engineering reversible serine protease inhibitors. When optimizing interactions between the inhibitor and target protease, many studies focus on the nonprimed segment of the inhibitor's binding loop (encompassing the contact β-strand). However, there are currently few methods for screening residues on the primed segment. Here, we designed a synthetic inhibitor library (based on sunflower trypsin inhibitor-1) for characterizing the P2′ specificity of various serine proteases. Screening the library against 13 different proteases revealed unique P2′ preferences for trypsin, chymotrypsin, matriptase, plasmin, thrombin, four kallikrein-related peptidases, and several clotting factors. Using this information to modify existing engineered inhibitors yielded new variants that showed considerably improved selectivity, reaching up to 7000-fold selectivity over certain off-target proteases. Our study demonstrates the importance of the P2′ residue in standard mechanism inhibition and unveils a new approach for screening P2′ substitutions that will benefit future inhibitor engineering studies.