Asymmetric phase-transfer-catalyzed synthesis of five-membered cyclic gamma-Amino acid precursors

The first example of an intramolecular enantioselective Michael addition of nitronates onto conjugated systems utilizing a chiral phase-transfer catalyst is described. A range of five-membered gamma-nitro esters with up to three stereocentres have been prepared and the relative and absolute configurations proven by chemical and crystallographic methods. The products are rapidly obtained and are precursors to five-membered cyclic gamma-amino acids

Diagnosing faults in autonomous robot plan execution

A major requirement for an autonomous robot is the capability to diagnose faults during plan execution in an uncertain environment. Many diagnostic researches concentrate only on hardware failures within an autonomous robot. Taking a different approach, the implementation of a Telerobot Diagnostic System that addresses, in addition to the hardware failures, failures caused by unexpected event changes in the environment or failures due to plan errors, is described. One feature of the system is the utilization of task-plan knowledge and context information to deduce fault symptoms. This forward deduction provides valuable information on past activities and the current expectations of a robotic event, both of which can guide the plan-execution inference process. The inference process adopts a model-based technique to recreate the plan-execution process and to confirm fault-source hypotheses. This technique allows the system to diagnose multiple faults due to either unexpected plan failures or hardware errors. This research initiates a major effort to investigate relationships between hardware faults and plan errors, relationships which were not addressed in the past. The results of this research will provide a clear understanding of how to generate a better task planner for an autonomous robot and how to recover the robot from faults in a critical environment

White coat hypertension is associated with increased small vessel disease in the brain

Objective: Small vessel disease, as measured by white matter hyperintensity (WMH) in the brain, is known to be associated with increased stroke risk and cognitive impairment. This study explored the relationship between WMH on computerised tomography (CT) and white coat hypertension/effect (WCH/E) in patients with recent transient ischaemic attack (TIA) or lacunar stroke (LS). Design and method: Ninety-six patients recruited for the ASIST trial (Arterial Stiffness in Lacunar Stroke and TIA) underwent measurement of clinic blood pressure (BP) and ambulatory BP monitoring (APBM) within two weeks of TIA or LS. Twenty-three patients had normotension (clinic BP / = 140/90mmHg and day-time ABPM < 135/85mmHg). Arterial stiffness was measured using carotid-femoral pulse wave velocity (PWV) (Complior®, ALAM Medical) and carotid-ankle vascular index (CAVI) (VaSera VS-1500N®, Fukuda Denshi). CT images were scored for WMH using the four-point Fazekas visual rating scale. Patients were grouped into no-mild WMH (scores 0–1) or moderate-severe (scores 2–3) groups. The relationship between BP, vascular stiffness and WMH was explored with t-tests, chi-square and logistic regression accounting for known cardiovascular risk factors. Results: Forty-four percent of patients with WCH/E had moderate-severe WMH compared to 17% of normotensives (p = 0.047). The regression model with WMH as the dependent factor, and WCH/E and cardiovascular risk factors as independent factors showed WCH/E and either CAVI or PWV to be the only independent significant factor contributing to WMH (CAVI:p = 0.038, PWV:p = 0.043)

P104 White coat hypertension is associated with increased small vessel disease in the brain

Objective: Small vessel disease, measured by brain white matter hyperintensity (WMH), is associated with increased stroke risk and cognitive impairment. This study aimed to explore the relationship between WMH on computerised tomography (CT) and white coat hypertension (WCH) in patients with recent transient ischaemic attack (TIA) or lacunar stroke (LS). Methods: Ninety-six patients recruited for the ASIST trial (Arterial Stiffness in Lacunar Stroke and TIA) underwent measurement of clinic blood pressure (BP) and ambulatory BP monitoring (APBM) within two weeks of TIA or LS. Patients were grouped by BP phenotypes. Twenty-three patients had normotension (clinic BP 140/90 mmHg and day-time ABPM <135/85 mmHg). CT brain images were scored for WMH using the four-point Fazekas visual rating scale. Patients were grouped into no-mild WMH (scores 0–1) or moderate-severe (scores 2–3) groups. The relationship between BP and WMH was explored with chi-square and logistic regression accounting for known cardiovascular risk factors (age, gender, smoking, diabetes and hyperlipidaemia). Results: 44% of WCH patients had moderate-severe WMH compared to 17% of normotensives (p = 0.047). Logistical regression incorporating WCH as the independent factor and cardiovascular risk factors as independent variables showed WCH to be the only independent significant factor contributing to WMH (p = 0.024). Conclusion: Patients with WCH were more likely to have moderate-severe WMH on CT brain than normotensives. WCH was associated with increased WMH, independent of other cardiovascular risk factors. This study suggests that WCH is associated with increased small vessel disease in the brain and may benefit from treatment

Regio- and stereocontrolled synthesis of 3-substituted 1,2-diazetidines by asymmetric allylic amination of vinyl epoxide

Pd-catalyzed asymmetric allylic amination of rac-vinyl epoxide with unsymmetrical 1,2-hydrazines proceeds with excellent regio- and stereocontrol, which after further ring closure provides differentially protected 3-vinyl-1,2-diazetidines in good yields. The chirality at C–3 exerts stereocontrol over the nitrogen centers in the 1,2-diazetidine with all substituents orientat-ing themselves trans to their neighbours. Efficient functionalization without rupture of the strained ring is demonstrated (e.g. by cross-metathesis), establishing the first general route to C–3 substituted 1,2-diazetidines in enantioenriched form

Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial

Objective To determine the efficacy of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use and that caused by Clostridium difficile. Design Randomised double blind placebo controlled study. Participants 135 hospital patients (mean age 74) taking antibiotics. Exclusions included diarrhoea on admission, bowel pathology that could result in diarrhoea, antibiotic use in the previous four weeks, severe illness, immunosuppression, bowel surgery, artificial heart valves, and history of rheumatic heart disease or infective endocarditis. Intervention Consumption of a 100 g (97 ml) drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus twice a day during a course of antibiotics and for one week after the course finished. The placebo group received a longlife sterile milkshake. Main outcome measures Primary outcome: occurrence of antibiotic associated diarrhoea. Secondary outcome: presence of C difficile toxin and diarrhoea. Results 7/57 (12%) of the probiotic group developed diarrhoea associated with antibiotic use compared with 19/56 (34%) in the placebo group (P=0.007). Logistic regression to control for other factors gave an odds ratio 0.25 (95% confidence interval 0.07 to 0.85) for use of the probiotic, with low albumin and sodium also increasing the risk of diarrhoea. The absolute risk reduction was 21.6% (6.6% to 36.6%), and the number needed to treat was 5 (3 to 15). No one in the probiotic group and 9/53 (17%) in the placebo group had diarrhoea caused by C difficile (P=0.001). The absolute risk reduction was 17% (7% to 27%), and the number needed to treat was 6 (4 to 14). Conclusion Consumption of a probiotic drink containing L casei, L bulgaricus, and S thermophilus reduce the incidence of antibiotic associated diarrhoea and C difficile associated diarrhoea. This has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50

Readily accessible sp3-rich cyclic hydrazine frameworks exploiting nitrogen fluxionality

Increased molecular complexity correlates with improved chances of success in the drug development process. Here, a strategy for the creation of sp3-rich, non-planar heterocyclic scaffolds suitable for drug discovery is described that obviates the need to generate multiple stereogenic centers with independent control. Asymmetric transfer hydrogenation using a tethered Ru-catalyst is used to efficiently produce a range of enantiopure cyclic hydrazine building blocks (up to 99% ee). Iterative C–N functionalization at the two nitrogen atoms of these compounds produces novel hydrazine and hydrazide based chemical libraries. Wide chemical diversification is possible through variation in the hydrazine structure, use of different functionalization chemistries and coupling partners, and controlled engagement of each nitrogen of the hydrazine in turn. Principal Moment of Inertia (PMI) analysis of this small hydrazine library reveals excellent shape diversity and three-dimensionality. NMR and crystallographic studies confirm these frameworks prefer to orient their substituents in three-dimensional space under the control of a single stereogenic center through exploitation of the fluxional behavior of the two nitrogen atoms

Prioritization Of Implementation Based Testing Technique For Class Under Test

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Prognostic Significance of Highly Sensitive C-Reactive Protein in Acute Ischemic Stroke Patients

INTRODUCTION: Stroke is now considered as an important health problem for all individuals and society. After Acute myocardial infarction and malignancy, Ischemic stroke is the third leading cause of death and is also as leading cause of hospitalization causing disability. So we have to identify the stroke at an earlier date which help the treating physicians to plan treatment, make interventions and to provide significant benefit to the people and community and to save the patient. The conventional risk factors namely blood pressure (BP), smoking, diabetes, dyslipidemia, alcohol predict the happening of stroke, but still they are not completely reliable, therefore there is a continuous debate and search for prediction of occurrence of stroke and reliability of prognostic markers in stroke have gained interest in recent years. When an individual is exposed to any insult in terms of infection and injury, there is a production of proteins called Acute Phase Proteins. This Acute phase protein participates in all inflammatory process and plays a major role in both acute and chronic inflammatory states. The Acute phase reactants are fibrinogen, ferritin, haptoglobin, highly sensitive C – reactive protein, Complements (C3), Complements (C4), Tumour necrosis factor. Among these various proteins, Highly sensitive C-reactive protein have gained wide recognition in monitoring different diseased states and it leads to the development of reliable and fast assay measuring their plasma levels. In recent years, inflammatory process plays an important role in pathophysiology of stroke. The initiator of extrinsic pathway of coagulation is Tissue factor. This tissue factor got expressed when mainly monocytes are stimulated by C-reactive protein and initiates vascular thrombosis. hsCRP, a marker of Atherosclerosis and also a peripheral marker of inflammation found to be valuable in sorting out of possible risk factors of subsequent cerebrovascular and cardiovascular (CV) events, Peripheral Arterial Diseases or death. This important fact was also supported by abundant laboratory and experimental evidence demonstrating that atherosclerosis refers to chronic inflammatory process. High plasma levels of CRP are not specific to disease, but it is sensitive marker and is produced in response to tissue injury, infectious agents and inflammation. hsCRP predicts the first cardiovascular event in general populations. hsCRP is the only inflammatory marker which independently predicts the future risk of stroke when measured prior to onset of clinical disease. AIMS & OBJECTIVES: 1) To evaluate the prognostic significance of hsCRP with severity of stroke in correlation with stroke scales (NIHSS and MRS). 2) To evaluate the relationship between hsCRP and various risk factors for stroke, with territory of infarct and other findings in CT film. MATERIALS AND METHODS: Setting: Patients admitted in medical ward, Government Rajaji Hospital, Madurai. Colaborative Departments: Department of Biochemistry, Neurology, Radiology, Medicine, Madurai Medical College, Madurai. Study Design: Prospective cross sectional observation study. Period of Study: March 2012 to October 2012. Study Population: 50 Acute ischemic stroke patients admitted in medical ward, Government Rajaji Hospital, Madurai. Inclusion Criteria: 1. All patients with new onset focal neurological deficit following ischemic stroke, presented within 48 hours of onset of stroke are taken into study. 2. Patients >14 years and of both sexes are included in the study. 3. Patients with new onset stroke with past history of hypertension, diabetes mellitus, dyslipidemeia, smoking, alcohol were included. Exclusion Criteria: 1. Patients with age more than 80 years were excluded. 2. Patients with malignancy and clinical findings and blood investigations suggestive of infection were excluded. 3. Individuals with Connective Tissue disorders and Rheumatic heart disease, Coronary Artery disease were excluded. 4. Patients with prior history of transient ischemic attacks or reversible ischemic neurological deficit, cerebrovascular accidents were excluded. 5. Patients with features of haemorrhage such as sub-dural haemorrhage, sub-arachnoid haemorrhage, and intracerebral haemorrhage were excluded with the aid of CT scan. 6. History of recent surgery and trauma. 7. CNS tumors. STUDY METHODS: 50 patients who had acute ischemic stroke were taken for study. Those patients who got admitted within 48 hours of onset of stroke were only included in this study. As soon as patient got admitted, verbal consent was obtained from patient or attenders. Then complete and relevant medical history, complete neurological examination, routine blood and radiological investigations were done and all data were recorded in a standardized proforma. RESULTS: Totally 50 cases were included in the study. Among the 50 cases included in this study 28 cases (56%) had hsCRP values ≥ 3 mg/l and 22 cases (44%) had hsCRP < 3 mg/l. Number of patients died in this group is 6. All these patients had a hsCRP of ≥ 3 mg/l. Out of these 28 cases who has hsCRP ≥ 3 mg/l, 26.67% of cases comes under moderately severe category and 73.33% cases comes under severe category. On the other hand, among the remaining 22 cases who had hsCRP <3mg/l, all the 22 cases comes under moderately severe and none in severe group. Pearson's r correlation also reveals the strong correlation between hsCRP and NIHSS scores. Pearson's r value is 0.844 which is close to one. A positive correlation exists between these 2 variables with a "p" value of 0.00, which is statistically significant. Scatter plot analysis reveals the positive correlation between hsCRP & NIHSS. Any increase or decrease in hsCRP score analogous linearly with increase/decrease severity score of NIHSS. Out of 28 cases with hsCRP ≥3 mg/l 4 cases were in good outcome category and 24 cases in poor outcome category of MRS scores. In contrast among 22 cases with hsCRP < 3 mg/l, 16 cases were in good outcome and 6 cases were in poor outcome category in MRS Score. Pearson‟s r correlation analysis reveals strong as well as positive correlation between hsCRP and MRS. Pearson‟s r value is 0.900 which is close to 1 and is positive variable. So any increase in hsCRP will favour the poor outcome of patients in terms of death and severe disability. CONCLUSION: This present study is a cross sectional observation study of prognostic significance of highly sensitive C-reactive protein in acute ischemic stroke patients. • The present study shows male predominance with majority of patients in the age group of greater than 50 years. • The present study revealed significant association between hsCRP and Diabetes Mellitus, Hypertension & Cholesterol level. • This study demonstrates the significant rise in hsCRP in ischemic stroke patients in correlation with high scores with NIHSS which indicates the severity. • This study reveals the poor outcome in correlation with high hsCRP values and good outcome in correlation with low hsCRP values. • This study also explains statistically significant relationship between hsCRP and infarct. • There is no statistically significant relationship between hsCRP and age, sex, smoking and alcohol