***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background — Recent evidence suggests that visit-to-visit variability in systolic blood pressure ( SBP ) and maximum SBP are predictors of cardiovascular disease . However , it remains uncertain whether these parameters predict the risks of macrovascular and microvascular complications in patients with type 2 diabetes mellitus . Methods and Results — The Action in Diabetes and Vascular Disease : Preterax and Diamicron Modified Release Controlled Evaluation ( ADVANCE ) was a factorial r and omized controlled trial of blood pressure lowering and blood glucose control in patients with type 2 diabetes mellitus . The present analysis included 8811 patients without major macrovascular and microvascular events or death during the first 24 months after r and omization .  SBP variability ( defined as st and ard deviation ) and maximum SBP were determined during the first 24 months after r and omization . During a median 2.4 years of follow-up from the 24-month visit , 407 major macrovascular ( myocardial infa rct ion , stroke , or cardiovascular death ) and 476 microvascular ( new or worsening nephropathy or retinopathy ) events were observed . The association of major macrovascular and microvascular events with SBP variability was continuous even after adjustment for mean SBP and other confounding factors ( both P<0.05 for trend ) . Hazard ratios ( 95 % confidence intervals ) for the highest tenth of SBP variability were 1.54 ( 0.99–2.39 ) for macrovascular events and 1.84 ( 1.19–2.84 ) for microvascular events in comparison with the lowest tenth . For maximum SBP , hazard ratios ( 95 % confidence intervals ) for the highest tenth were 3.64 ( 1.73–7.66 ) and 2.18 ( 1.04–4.58 ) , respectively . Conclusion — Visit-to-visit variability in SBP and maximum SBP were independent risk factors for macrovascular and microvascular complications in type 2 diabetes mellitus . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique Identifier : NCT00145925 To assess the prognostic significance of blood pressure  ( BP ) variability , we followed health outcomes in a family-based r and om population sample representative of the general population ( n=2944 ; mean age : 44.9 years ; 50.7 % women ) . At baseline , BP was measured 5 times consecutively at each of 2 home visits 2 to 4 weeks apart . We assessed within-subject overall ( 10 readings ) , within- and between-visit  systolic BP variability  from variability independent of the mean , the difference between maximum and minimum BP , and average real variability . Over a median follow-up of 12 years , 401 deaths occurred and 311 participants experienced a fatal or nonfatal cardiovascular event . Overall systolic BP variability averaged ( SD ) 5.45 ( 2.82 ) units , 15.87 ( 8.36 ) mmHg , and 4.08 ( 2.05 ) mmHg for variability independent of the mean , difference between maximum and minimum BP , and average real variability , respectively . Female sex , older age , higher-mean systolic BP , lower body mass index , a history of peripheral arterial disease , and use of & bgr;-blockers were the main correlates of systolic BP variability . In multivariable-adjusted analyses , overall and within- and between-visit BP variability did not predict total or cardiovascular mortality or the composite of any fatal plus nonfatal cardiovascular end point . For instance , the hazard ratios for all cardiovascular events combined in relation to overall variability independent of the mean , difference between maximum and minimum BP , and average real variability were 1.05 ( 0.96–1.15 ) , 1.06 ( 0.96–1.16 ) , and 1.08 ( 0.98–1.19 ) , respectively . By contrast , mean systolic BP was a significant predictor of all end points under study , independent of BP variability . In conclusion , in an unbiased population sample , BP variability did not contribute to risk stratification over and beyond mean systolic BP Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects , but relevant data for older individuals are sparse . We analysed data from the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) study of 5804 participants aged 70–82 years with a history of , or risk factors for cardiovascular disease . Visit-to-visit variability in blood pressure ( st and ard deviation ) was determined using a minimum of five measurements over 1 year ; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up ; longer-term follow-up ( mean 7.1 years ) was available for 1808 subjects .  Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality ( hazard ratio per 5 mmHg increase in st and ard deviation of systolic blood pressure = 1.2 , 95 % confidence interval 1.1–1.4 ; hazard ratio 1.1 , 95 % confidence interval 1.1–1.2 , respectively ) . Variability in diastolic blood pressure associated with increased risk for coronary events ( hazard ratio 1.5 , 95 % confidence interval 1.2–1.8 for each 5 mmHg increase ) , heart failure hospitalisation ( hazard ratio 1.4 , 95 % confidence interval 1.1–1.8 ) and vascular ( hazard ratio 1.4 , 95 % confidence interval 1.1–1.7 ) and total mortality ( hazard ratio 1.3 , 95 % confidence interval 1.1–1.5 ) , all in long-term follow-up . Pulse pressure variability was associated with increased stroke risk ( hazard ratio 1.2 , 95 % confidence interval 1.0–1.4 for each 5 mmHg increase ) , vascular mortality ( hazard ratio 1.2 , 95 % confidence interval 1.0–1.3 ) and total mortality ( hazard ratio 1.1 , 95 % confidence interval 1.0–1.2 ) , all in long-term follow-up . All associations were independent of respective mean blood pressure levels , age , gender , in-trial treatment group ( pravastatin or placebo ) and prior vascular disease and cardiovascular disease risk factors . Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects Visit-to-visit blood pressure variability ( VTV-BPV ) is an independent risk factor for cardiovascular events and death in the general population . We sought to determine the association of VTV-BPV with outcomes in patients on hemodialysis , using data from a National Institutes of Health-sponsored r and omized trial ( the HEMO study ) . We used the coefficient of variation ( CV ) and the average real variability in systolic blood pressure ( SBP ) as metrics of VTV-BPV . In all , 1844 out of 1846 r and omized subjects had at least three visits with SBP measurements and were included in the analysis . Median follow-up was 2.5 years ( interquartile range 1.3–4.3 years ) , during which time there were 869 deaths from any cause and 408 ( adjudicated ) cardiovascular deaths . The mean pre-dialysis SBP CV was 9.9±4.6 % . In unadjusted models , we found a 31 % higher risk of death from any cause per 10 % increase in VTV-BPV . This association was attenuated after multivariable adjustment but remained statistically significant . Similarly , we found a 28 % higher risk of cardiovascular death per 10 % increase in VTV-BPV , which was attenuated and no longer statistically significant in fully adjusted models . The associations among VTV-BPV , death and cardiovascular death were modified by baseline SBP . In a diverse , well-dialyzed cohort of patients on maintenance hemodialysis , VTV-BPV , assessed using metrics of variability in pre-dialysis SBP , was associated with a higher risk of all-cause mortality and a trend toward higher risk of cardiovascular mortality , particularly in patients with a lower baseline SBP Objective To investigate whether baseline systolic blood pressure variability was a risk factor for stroke , cardiovascular mortality or cardiac events during the Syst-Eur trial . Design The Syst-Eur study was a r and omized , double-blind , placebo-controlled trial , powered to detect differences in stroke rate between participants on active antihypertensive treatment and placebo .  Systolic blood pressure variability measurements were made on 744 participants at the start of the trial . Systolic blood pressure variability was calculated over three time frames : 24 h , daytime and night-time . The placebo and active treatment subgroups were analysed separately using an intention-to-treat principle , adjusting for confounding factors using a multiple Cox regression model . Participants An elderly hypertensive European population . Main outcome measures Stroke , cardiac events ( fatal and non-fatal heart failure , fatal and non-fatal myocardial infa rct ion and sudden death ) and cardiovascular mortality ( death attributed to stroke , heart failure , myocardial infa rct ion , sudden death , pulmonary embolus , peripheral vascular disease and aortic dissection ) . Results The risk of stroke increased by 80 % ( 95 % confidence interval : 17–176 % ) for every 5 mmHg increase in night-time systolic blood pressure variability in the placebo group . Risk of cardiovascular mortality and cardiac events was not significantly altered . Daytime variability readings did not predict outcome . Antihypertensive treatment did not affect systolic blood pressure variability over the median 4.4-year follow-up . Conclusion In the placebo group , but not the active treatment group , increased night-time systolic blood pressure variability on admission to the Syst-Eur trial was an independent risk factor for stroke during the trial Objective : To assess how visit-to-visit variability of SBP correlates with systemic atherosclerotic change and various prognoses . Background : Visit-to-visit SBP variability correlates with cardiovascular events . However , the mechanisms underlying the impact of visit-to-visit SBP variability on prognoses are poorly understood . Methods and results : A total of 485 patients with essential hypertension from the Non-Invasive Atherosclerotic Evaluation in Hypertension ( NOAH ) study cohort were included . We analyzed the correlation between visit-to-visit SBP variability and multiple clinical parameters . Next , we prospect ively examined the correlation of SBP variability and frequency of cardiovascular disease ( CVD ) and total mortality . Patients with higher SBP variability exhibited significantly higher rates of statin use , as well as higher pulse wave velocity ( PWV ) , left-ventricular mass index ( LVMI ) , plaque score , and resistive index of the common carotid artery ; these patients also exhibited lower estimated glomerular filtration rate . Kaplan – Meier analysis demonstrated that patients with higher SBP variability have a significantly higher incidence of CVD and mortality rate . The hazard ratio of SBP variability for incidence of CVD was greatly diminished after adjustment for intima – media thickness , plaque score , and resistive index , and was slightly diminished after adjustment for PWV and LVMI . Visit-to-visit SBP variability remained an independent risk factor for mortality after adjustment . Conclusion : Visit-to-visit SBP variability correlates significantly with systemic atherosclerotic change , incidence of CVD , and mortality rate . Altered arterial functions , such as macrovascular atherosclerosis and vascular resistance , are responsible for the correlations between visit-to-visit SBP variability and incidence of CVD Introduction : Fluorescence in situ hybridization ( FISH ) is currently the st and ard for diagnosing anaplastic lymphoma kinase (ALK)-rearranged ( ALK+ ) lung cancers for ALK inhibitor therapies . ALK immunohistochemistry ( IHC ) may serve as a screening and alternative diagnostic method . The Canadian ALK ( CALK ) study was initiated to implement a multicenter optimization and st and ardization of laboratory developed ALK IHC and FISH tests across 14 hospitals . Methods : Twenty-eight lung adenocarcinomas with known ALK status were used as blinded study sample s. Thirteen laboratories performed IHC using locally developed staining protocol s for 5A4 , ALK1 , or D5F3 antibodies ; results were assessed by H-score . Twelve centers conducted FISH using protocol s based on Vysis ’ ALK break-apart FISH kit . Initial IHC results were used to optimize local IHC protocol s , followed by a repeat IHC study to assess the results of st and ardization . Three laboratories conducted a prospect i ve parallel IHC and FISH analysis on 411 consecutive clinical sample s using post-validation optimized assays . Results : Among study sample s , FISH demonstrated 22 consensus ALK+ and six ALK wild type tumors . Preoptimization IHC scores from 12 centers with 5A4 and the percent abnormal cells by FISH from 12 centers showed intraclass correlation coefficients of 0.83 and 0.68 , respectively . IHC optimization improved the intraclass correlation coefficients to 0.9 
    Output:
    
Conclusion : In summary , among the wide heterogenetic population , modest associations between VVV of SBP and all-cause mortality , CVD incidence , CVD mortality , CHD incidence , and stroke incidence were found .