Laboratory Experiments and Grain Based Discrete Element Numerical Simulations Investigating the Thermo-Mechanical Behaviour of Sandstone.

Thermo-mechanical loading can occur in numerous engineering geological environments, from both natural and anthropogenic sources. Different minerals and micro-defects in rock cause heterogeneity at a grain scale, affecting the mechanical and thermal properties of the material. Changes in strength and stiffness can occur from exposure to elevated temperatures, with the accumulation of localised stresses resulting in thermally induced micro-cracking within the rock. In this study we investigated thermal micro-cracking at a grain scale through both laboratory experiments and their numerical simulations. We performed laboratory triaxial experiments on specimens of fine-grained sandstone at a confining pressure of 5 MPa and room temperature (20 ∘ C ), as well as heating to 50 ∘ C , 75 ∘ C and 100 ∘ C prior to mechanical loading. The laboratory experiments were then replicated using discrete element method simulations. The geometry and granular structure of the sandstone was replicated using a Voronoi tessellation scheme to produce a grain based model. Strength and stiffness properties of the Voronoi contacts were calibrated to the laboratory specimens. Grain scale thermal properties were applied to the grain based models according to mineral percentages obtained from quantitative X-ray diffraction analysis on laboratory specimens. Thermo-mechanically coupled modelling was then undertaken to reproduce the thermal loading rates used in the laboratory, before applying a mechanical load in the models until failure. Laboratory results show a reduction of up to 15% peak strength with increasing thermal loading between room temperature and 100 ∘ C , and micro-structural analysis shows the development of thermally induced micro-cracking in laboratory specimens. The mechanical numerical simulations calibrate well with the laboratory results, and introducing coupled thermal loading to the simulations shows the development of localised stresses within the models, leading to the formation of thermally induced micro-cracks and strength reduction upon mechanical loading.

The Acute Kidney Outreach to Prevent Deterioration and Death trial: a large pilot study for a cluster-randomized trial.

BACKGROUND AND OBJECTIVES: The Acute Kidney Outreach to Reduce Deterioration and Death trial was a large pilot study for a cluster-randomized trial of acute kidney injury (AKI) outreach. METHODS: An observational control (before) phase was conducted in two teaching hospitals (9 miles apart) and their respective catchment areas. In the intervention (after) phase, a working-hours AKI outreach service operated for the intervention hospital/area for 20 weeks, with the other site acting as a control. All AKI alerts in both hospital and community patients were screened for inclusion. Major exclusion criteria were patients who were at the end of life, unlikely to benefit from outreach, lacking mental capacity or already referred to the renal team. The intervention arm included a model of escalation of renal care to AKI patients, depending on AKI stage. The 30-day primary outcome was a combination of death, or deterioration, as shown by any need for dialysis or progression in AKI stage. A total of 1762 adult patients were recruited; 744 at the intervention site during the after phase. RESULTS: A median of 3.0 non-medication recommendations and 0.5 medication-related recommendations per patient were made by the outreach team a median of 15.7 h after the AKI alert. Relatively low rates of the primary outcomes of death within 30 days (11-15%) or requirement for dialysis (0.4-3.7%) were seen across all four groups. In an exploratory analysis, at the intervention hospital during the after phase, there was an odds ratio for the combined primary outcome of 0.73 (95% confidence interval 0.42-1.26; P = 0.26). CONCLUSIONS: An AKI outreach service can provide standardized specialist care to those with AKI across a healthcare economy. Trials assessing AKI outreach may benefit from focusing on those patients with 'mid-range' prognosis, where nephrological intervention could have the most impact.

Diagnosis and Management of Iron Deficiency in CKD: A Summary of the NICE Guideline Recommendations and Their Rationale.

The UK-based National Institute for Health and Care Excellence (NICE) has updated its guidance on iron deficiency and anemia management in chronic kidney disease. This report outlines the recommendations regarding iron deficiency and their rationale. Serum ferritin alone or transferrin saturation alone are no longer recommended as diagnostic tests to assess iron deficiency. Red blood cell markers (percentage hypochromic red blood cells, reticulocyte hemoglobin content, or reticulocyte hemoglobin equivalent) are better than ferritin level alone at predicting responsiveness to intravenous iron. When red blood cell markers are not available, a combination of transferrin saturation < 20% and ferritin level < 100ng/mL is an alternative. In comparisons of the cost-effectiveness of different iron status testing and treatment strategies, using percentage hypochromic red blood cells > 6% was the most cost-effective strategy for both hemodialysis and nonhemodialysis patients. A trial of oral iron replacement is recommended in people not receiving an erythropoiesis-stimulating agent (ESA) and not on hemodialysis therapy. For children receiving ESAs, but not treated by hemodialysis, oral iron should be considered. In adults and children receiving ESAs and/or on hemodialysis therapy, intravenous iron should be offered. When giving intravenous iron, high-dose low-frequency administration is recommended. For all children and for adults receiving in-center hemodialysis, low-dose high-frequency administration may be more appropriate.

The definition of acute kidney injury and its use in practice.

Acute kidney injury (AKI) is a common syndrome that is independently associated with increased mortality. A standardized definition is important to facilitate clinical care and research. The definition of AKI has evolved rapidly since 2004, with the introduction of the Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) classifications. RIFLE was modified for pediatric use (pRIFLE). They were developed using both evidence and consensus. Small rises in serum creatinine are independently associated with increased mortality, and hence are incorporated into the current definition of AKI. The recent definition from the international KDIGO guideline merged RIFLE and AKIN. Systematic review has found that these definitions do not differ significantly in their performance. Health-care staff caring for children or adults should use standard criteria for AKI, such as the pRIFLE or KDIGO definitions, respectively. These efforts to standardize AKI definition are a substantial advance, although areas of uncertainty remain. The new definitions have enabled the use of electronic alerts to warn clinicians of possible AKI. Novel biomarkers may further refine the definition of AKI, but their use will need to produce tangible improvements in outcomes and cost effectiveness. Further developments in AKI definitions should be informed by research into their practical application across health-care providers. This review will discuss the definition of AKI and its use in practice for clinicians and laboratory scientists.

Earlier intervention for acute kidney injury: evaluation of an outreach service and a long-term follow-up.

BACKGROUND: There have been few studies of earlier systematic intervention to reduce the impact of acute kidney injury (AKI). In 2009, we piloted an AKI outreach service with a before and after study, and we report on the study and its longer-term follow-up. METHODS: AKI patients were identified using a laboratory delta check for creatinine of 75%. In the 4-week before phase patients received standard care. In a consecutive 7-week after phase an outreach team of nephrology doctors and nurses reviewed all alerts twice daily, 5 days a week. The primary clinical team caring for the patient was called to be given advice on AKI care. RESULTS: There were 157 and 251 patients in the before and after groups, respectively, who were comparable in their characteristics. The mean age was 70 years in both groups and ∼ 80% of each group were admitted to the hospital. In the after group, the Outreach telephone call was successful in 88%, at a median of 14 h. Substantial numbers of recommendations were made, largely related to fluid balance, investigations and medication use. Survival showed an immediate non-significant improvement in the after group, but converged at about 4 years. CONCLUSION: Outreach shows potential to improve outcomes in AKI. In order to achieve this it seems likely that at least a five-day per week service will be needed to assist good renal and general medical care for this vulnerable group.

Does community-wide chronic kidney disease management improve patient outcomes?

BACKGROUND: The number of patients starting renal replacement therapy (RRT) is increasing in England, as it is worldwide. Improvements in the management of chronic kidney disease (CKD) across communities to alter this trend are a public health priority. We have prospectively studied changes in the incidence and modality of treatment for end-stage renal disease following the introduction of a CKD management programme in the West Midlands region of England. METHODS: Nephrology service to approximately 700 000 adult population of mixed ethnicity in urban and suburban areas, many with social deprivation. The programme was introduced in stages between 2003 and 2006 and comprised primary care education and financial incentives, personal clinical reports written directly to patients following every consultation, routine laboratory estimated glomerular filtration rate (eGFR) reporting, eGFR graph surveillance to identify and monitor patients at risk, multidisciplinary pre-RRT care and conservative care. Prevalent patients: 10 552 with CKD and 8509 without CKD with diabetes. OUTCOMES: access to nephrology care, trends in RRT incidence and starting modality, place of death without RRT. Incident count was adjusted for changes in the local adult population recorded in national censuses. RESULTS: Ninety-one per cent of patients aged ≥75 years with incident CKD stage 5 were known to a nephrologist. The population-adjusted incident RRT rate peaked in 2005 and then declined; the proportion starting with transplant, peritoneal dialysis or haemodialysis by arterio-venous fistula increased to 63% by 2012 (P = 0.001 versus 2005). Fifty-two per cent of patients receiving planned conservative care without dialysis died out of hospital. CONCLUSIONS: Following the introduction of a community-wide systematic CKD management programme, the population-adjusted incidence of RRT reduced, modality of initiation of RRT improved and a majority of patients receiving planned conservative care without dialysis died out of hospital.

LED controlled flow photolysis for concentration gradients in microfluidic systems.

Many of the channels and reservoirs in microfluidic systems are used simply to allow liquids with different compositions to be delivered to where they are needed. An alternative approach is to use dissolved photochemicals and variable intensity LEDs to generate composition changes in situ. We applied this approach to generate concentration gradients of HCl for gradient ion chromatography.

Effect of ramipril on renal function in patients with intermittent claudication.

BACKGROUND: The Heart Outcomes Prevention Study (HOPE) demonstrated that ramipril resulted in a blood-pressure-independent 25% reduction in cardiovascular events in patients with peripheral arterial disease (PAD). Despite this, general practitioners and vascular surgeons remain reluctant to prescribe ACE inhibitors in this group of patients because of concerns about renal artery stenosis (RAS). We aimed to define the effect of ramipril on renal function in patients with intermittent claudication (IC). METHODS AND RESULTS: Of 132 unselected patients with IC entering the study 78 (59%) were excluded due to: current ACE inhibitor use (38%), renal impairment (serum creatinine above normal range) (15%), known severe RAS (1%) or unwillingness to participate (5%). The remaining 54 patients were titrated to 10 mg ramipril and renal function was monitored at 1, 5, and 12 weeks. Treatment was discontinued during titration in 5 patients due to symptoms (3) or lack of compliance (2). In the remainder, median [IQR] serum creatinine increased (94 [85.8-103.3] to 98 [88.0-106.5] micromol/L, p < or = 0.001) and median [IQR] GFR decreased (71.5 [64.6-82.3] to 68.7 [59.8-74.7] mL/min per 1.73 m2, p < or = 0.001) between baseline and 5 weeks. These changes were not considered clinically significant. By 12 weeks these values had returned almost to baseline (Cr 95.5 [88.0-103.25] micromol/L, GFR 71.8 [65.3-77.4] mL/min). No patient had a serum creatinine rise > 30%. CONCLUSION: Most of patients with IC and a normal serum creatinine can be safely commenced on ramipril provided they are screened, titrated and monitored as described above. Studies in patients with borderline renal impairment (serum creatinine up to 30% above baseline) are on-going.

Fatty acids exacerbate tubulointerstitial injury in protein-overload proteinuria.

The role of the albumin-carried fatty acids in the induction of tubulointerstitial injury was studied in protein-overload proteinuria. Rats were injected with fatty acid-carrying BSA [FA(+)BSA], fatty acid-depleted BSA [FA(-)BSA], or saline. Macrophage infiltration was measured by immunohistochemical staining, apoptotic cells were detected by in situ end labeling, and proliferating cells were identified by in situ hybridization for histone mRNA. Macrophage infiltration was significantly greater in the FA(+)BSA group than in the FA(-)BSA and saline groups. The infiltrate was largely restricted to the outer cortex. Apoptosis was greater in the FA(+)BSA group than in the FA(-)BSA and saline groups. Compared with the saline group, apoptosis was significantly increased in the FA(+)BSA group but not in the FA(-)BSA group. Cortical cells proliferated significantly more in the FA(+)BSA and FA(-)BSA groups than in the saline group. FA(+)BSA is therefore a more potent inducer of macrophage infiltration and cell death than FA(-)BSA. The fatty acids carried on albumin may be the chief instigators of tubulointerstitial injury in protein-overload proteinuria.