Ef?cacy and Safety of Alirocumab Versus Ezetimibe Over2Years(from ODYSSEY COMBO II) Mahfouz El Shahawy,MD a,*,Christopher P.Cannon,MD b,Dirk J.Blom,MMed,PhD c, James M.McKenney,PharmD d,Bertrand Cariou,MD,PhD e,Guillaume Lecorps,MSc f, Robert Pordy,MD g,Umesh Chaudhari,MD h,and Helen M.Colhoun,MD i
The proprotein convertase subtilisin/kexin type9inhibitor alirocumab has been shown to substantially reduce low-density lipoprotein cholesterol(LDL-C).Demonstrating whether ef?cacy and safety are maintained over a long duration of exposure is vital for clinical decision-making.The COMBO II trial compared the ef?cacy and safety of alirocumab versus ezetimibe over2years.A prespeci?ed?rst analysis was reported at52weeks.Here we report the?nal end-of-study data(on-treatment)and evaluate post hoc the safety pro?le with longer versus shorter duration of alirocumab exposure.Patients(n=720)on maximally tolerated statin dose were treated with alirocumab(75/150mg every2weeks) or ezetimibe(10mg/day).Overall mean adherence for both treatment groups during the ?rst and second year was>97%.At2years,LDL-C was reduced by49%(alirocumab) versus17%(ezetimibe;p<0.0001),and LDL-C<70mg/dl was achieved by73%of alirocumab-treated versus40%of ezetimibe-treated patients.Overall safety was similar in both treatment groups at2years and during the?rst versus the second year.Local injection-site reactions were reported by2.5%(alirocumab)versus0.8%(ezetimibe)during the ?rst year,and0.2%versus0.5%during the second year,indicating early occurrence during prolonged alirocumab exposure.Two consecutive calculated LDL-C values<25mg/ dl were observed in28%of alirocumab-treated patients(vs0.4%with ezetimibe).Persistent anti-drug antibody responses were observed in1.3%(6of454)of alirocumab-treated versus0.4%(1of231)of ezetimibe-treated patients.Neutralizing antibodies(that inhibit binding in vitro)were observed in1.5%(7of454)of alirocumab-treated patients(0with ezetimibe),mostly at isolated time points.Alirocumab sustained substantial LDL-C reduc-tions and was well tolerated up to2years in the COMBO II trial.?2017The Authors.
Published by Elsevier Inc.This is an open access article under the CC BY-NC-ND license (https://www.doczj.com/doc/cc16915121.html,/licenses/by-nc-nd/4.0/).(Am J Cardiol2017;120:931–939)
Alirocumab,a proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitor,reduces low-density lipoprotein cho-lesterol(LDL-C)levels by up to61%in addition to statins±lipid-lowering therapies.1–3The ODYSSEY Phase3 COMBO II(NCT01644188)trial evaluated the ef?cacy and safety of alirocumab versus ezetimibe in reducing LDL-C in patients at high risk of cardiovascular(CV)events on maxi-mally tolerated statin dose(MTD,de?ned in the supplement) who were not at pre-speci?ed LDL-C target levels.4,5At24 weeks,alirocumab reduced LDL-C by51%(vs21%with ezetimibe),corresponding to achieved LDL-C levels of 52mg/dl and83mg/dl,respectively.4An important consid-eration is whether the number and nature of adverse events (AEs)change following long-term alirocumab exposure, considering the recent data on the variability in ef?cacy and AEs related to immunogenicity seen on treatment with bococizumab,another PCSK9antibody.6,7Here we report the ?nal end-of-study ef?cacy and safety data from the COMBO II trial to evaluate whether the effect of alirocumab versus ezetimibe is sustained for up to2years.We also compared post hoc the treatment adherence,safety,and the incidence of AEs in the?rst year versus the second year of the study. Methods
Detailed methods and patient disposition have been re-ported previously(Figure1).4,5Brie?y,the multinational, multicenter,double-blind,active controlled,parallel-group study included patients with hypercholesterolemia and es-tablished coronary heart disease(CHD;de?ned in the Supplement)or CHD risk equivalents(ischemic stroke,pe-ripheral artery disease,moderate chronic kidney disease,or diabetes mellitus plus≥2additional risk factors)not at Na-tional Cholesterol Education Program,Adult Treatment Panel III goal despite stable MTD for≥4weeks before the screen-ing visit.The goal for patients with documented CV disease was LDL-C<70mg/dl,or<100mg/dl for patients without
a Cardiovascular Center of Sarasota,Sarasota,Florida;
b Harvard Clini-
cal Research Institute,Boston,Massachusetts;c Division of Lipidology,
Department of Medicine,University of Cape Town and MRC Cape Heart
Group,Cape Town,South Africa;d Virginia Commonwealth University and
National Clinical Research,Inc.,Richmond,Virginia;e L’Institut du Thorax,
CHU de Nantes,Nantes,France;f Sano?,Chilly–Mazarin,France;g Regeneron
Pharmaceuticals,Inc.,Tarrytown,New York;h Sano?,Bridgewater,New
Jersey;and i University of Edinburgh,Edinburgh,UK.Manuscript received
March31,2017;revised manuscript received and accepted June8,2017.
The study was funded by Sano?and Regeneron Pharmaceuticals,Inc.
See page937for disclosure information.
*Corresponding author:Tel:(941)366-9800;fax:(941)366-2781.
E-mail address:mshahawy@https://www.doczj.com/doc/cc16915121.html,(M.El Shahawy).
0002-9149/?2017The Authors.Published by Elsevier Inc.This is an open access article
under the CC BY-NC-ND license(https://www.doczj.com/doc/cc16915121.html,/licenses/by-nc-nd/4.0/).
https://www.doczj.com/doc/cc16915121.html,
a documented history of CV disease but at high CV risk.CV disease was de?ned as CHD,ischemic stroke,or peripheral artery disease.
Patients (n =720)were randomized 2:1to receive double-blind treatment for 2years with either subcutaneous alirocumab 75mg (in 1-ml volume)every 2weeks (Q2W)(plus oral placebo for ezetimibe daily)or 10mg oral ezetimibe daily (plus placebo subcutaneous Q2W for alirocumab)and con-tinued to receive their background statin therapy.At week 12,the alirocumab dose was automatically increased to 150mg Q2W (1-ml volume)if the week 8LDL-C value was ≥70mg/dl,while maintaining subject and investigator blind-ing.There was an 8-week posttreatment observation period following the 2-year (104-week)double-blind period.The pro-tocol was approved by the institutional review boards of participating centers.All participants gave written informed consent.Race was self-reported in this study.
The primary end point was percentage change in calcu-lated LDL-C from baseline to week 24,using all LDL-C values regardless of adherence to treatment (intent-to-treat [ITT]ap-proach)and has been published previously.4Here,we report percentage change in calculated LDL-C from baseline up to 2years by on-treatment analysis.For the on-treatment analy-sis,changes in lipoprotein values during the ef?cacy treatment period were assessed using the modi?ed ITT population,de?ned as all randomized patients who received at least 1dose or part of a dose of the double-blind study treatment and had an evaluable primary ef?cacy end point during the treat-ment period (de?ned as the period ending at last injection date +21days or last capsule administration date +3days,which-ever comes ?rst).The primary ef?cacy end point was evaluated when both baseline and at least 1calculated LDL-C value on-treatment (during the ef?cacy period and within 1of the analysis windows up to 2years)were both available.Per-centage changes in apolipoprotein (Apo)B,high-density lipoprotein cholesterol (HDL-C),lipoprotein(a)(Lp[a]),non–HDL-C,triglycerides,and Apo A1from baseline to 2years are also reported (on-treatment analysis).
The overall treatment adherence for injections was de?ned during the treatment period for each patient as follows:100?(percentage of days with below-planned dosing +percent-age of days with above-planned dosing).Overall treatment adherence rates were analyzed in the ?rst (weeks 0to 52)and second (weeks 52to 104)years of treatment (further details in the Supplement).Safety was assessed by analyzing AE reports and laboratory analyses from the time of signed in-formed consent until the end of the study.AEs were de?ned as treatment-emergent if they developed,worsened,or became serious during the period between ?rst and last dose of study treatment (planned at week 102)plus 10weeks (further details in the Supplement).
In addition to overall AE rates up to the end of the study,we also compared (post hoc)the rates of AEs in the ?rst year (weeks 0to 56)versus the second year (weeks 56to 112)of the study.If a patient had an event once during weeks 0to 56and once during weeks 56to 112,the 2events were ana-lyzed separately in the respective time period in which they occurred.Although the last treatment dose was at week
102,
Figure 1.Consolidated Standards of Reporting Trials ?ow diagram.Patient disposition of the study population.AE =adverse event;ITT =intent to treat;mITT =modi?ed intent to treat;Q2W =every 2weeks.
932The American Journal of Cardiology (https://www.doczj.com/doc/cc16915121.html, )
residual effect of alirocumab is expected until10weeks after the last injection.The AE follow-up period is8weeks fol-lowing the end-of-treatment visit at week104;hence,the overall study period was up to112weeks.A comparison between weeks0to56and weeks56to112was used to allow for equal periods of treatment duration.
The presence of anti-drug antibodies(ADAs)was evalu-ated at weeks0,12,24,52,and104using a validated,titer-based immunoassay(sensitivity~5ng/ml;Regeneron Pharmaceuticals,Inc.,Tarrytown,NY;assay details in the Supplement and as reported previously8).A persistent ADA response was de?ned as2consecutive positive postbaseline responses separated by a minimum of12weeks.Samples posi-tive for ADAs were further examined for neutralizing antibodies(NAbs),which are ADAs that inhibit the binding of alirocumab to PCSK9in vitro(assay details in the Supple-ment and previously reported8).
All statistical analyses were performed by Sano?at the direction of the independent investigators,who had access to any relevant data analysis on request in this study.Statis-tical analyses have been described previously.4,5A mixed-effect model with repeated measures was used to compare changes in LDL-C and other lipoproteins assumed to be nor-mally distributed between alirocumab and ezetimibe patient groups over2years.Lipoproteins assumed to be non-normally distributed(i.e.,triglycerides and Lp[a])were analyzed using multiple imputation to handle missing data followed by robust regression model.
Results
Demographic characteristics,disease characteristics,and lipid parameters at baseline were generally similar in the alirocumab group compared with the ezetimibe group,and have been reported previously.4Mean(standard deviation[SD]) age at screening was62(9.3)years,74%were male,and85% were white.Mean(SD)baseline LDL-C levels were109(37) and105(34)mg/dl in the alirocumab(n=479)and ezetimibe (n=241)groups,respectively(Table S1in the Supplement).
Atherosclerotic cardiovascular disease(ASCVD),which included CHD,ischemic stroke,and peripheral arterial disease, was documented in95%of patients.Of the total popula-tion,81%had hypertension and31%had investigator-reported type2diabetes mellitus(de?ned by medical history, Table S1in the Supplement).
Exposure to investigational medical product injections with ≥102weeks’duration was observed in79%(378of479)and 78%(187of241)of alirocumab-and ezetimibe-treated pa-tients,respectively.Exposure to investigational medical product capsules with≥102weeks’duration was observed in81%(381 of472)and79%(187of237)of alirocumab-and ezetimibe-treated patients,respectively.
The overall mean(SD)treatment adherence over2years was high in both groups:98%(5.1)for the alirocumab-treated and98%(3.5)for the ezetimibe-treated group.The majority of patients in the alirocumab(98%)and ezetimibe (99%)groups had at least80%adherence for injections(i.e., patients received≥80%of their injections on schedule).Simi-larly,96%of alirocumab-treated and98%of ezetimibe-treated patients had at least80%adherence for capsules.There was no difference in treatment adherence between the?rst year and the second year of treatment.The overall mean(SD) treatment adherence for both treatment groups during the?rst and second year of treatment was>97%.The percentage of patients with≥80%adherence for injections was99%for both the alirocumab and the ezetimibe groups during the?rst year and99%and98%,respectively,during the second year.Simi-larly,the percentage of alirocumab-treated patients with≥80% adherence for capsules was97%(vs99%ezetimibe-treated) during the?rst year and97%(vs98%ezetimibe-treated) during the second year.
In the on-treatment analysis,LDL-C was reduced from baseline to week24by52%with alirocumab versus22%with ezetimibe(least squares[LS]mean difference of?31%,95% con?dence interval[CI]?35to?26;p<0.0001;Figure2).
A sustained effect of alirocumab was observed on calcu-lated LDL-C over2years with reductions of49%versus17% with ezetimibe at2years(LS mean difference of?32%,95% CI?38to?26;p<0.0001;Figure1,Table S2in the Supple-ment).Alirocumab treatment for2years resulted in mean (standard error)calculated LDL-C values of54(1.8)mg/dl versus87(2.6)mg/dl on ezetimibe treatment(p<0.0001). LDL-C<70mg/dl was achieved by73%of alirocumab-treated versus40%of ezetimibe-treated patients at2years.
Signi?cant(p<0.0001)reductions from baseline up to2 years were observed in Lp(a),Apo B,and non–HDL-C levels, whereas HDL-C levels signi?cantly(p<0.0001)increased with alirocumab versus ezetimibe treatment(LS mean difference of+7.4%for percent change from baseline at2years, Figures2).Triglycerides were reduced from baseline to2years by8.2%in the alirocumab group and by11.4%in the ezetimibe group,but the difference between treatment arms was not statistically signi?cant(Figure2).
Over the course of the whole study period,AEs were re-ported by391(82%)alirocumab-treated versus198(82%) ezetimibe-treated patients,and serious AEs were reported by 124(26%)versus60(25%)patients,respectively.AEs leading to death occurred in6(1.3%)alirocumab-treated versus6 (2.5%)ezetimibe-treated patients,and AEs leading to dis-continuation of study treatment occurred in44(9.2%)versus 19(7.9%)patients,respectively(Table1).
In AEs of interest,higher rates were observed with alirocumab versus ezetimibe for injection-site reactions and allergic reactions(Table1).Cataract conditions were ob-served in10(2.1%)alirocumab-treated and6(2.5%) ezetimibe-treated patients.Single elevations of alanine and aspartate aminotransferase were observed at higher frequen-cies with alirocumab versus ezetimibe,whereas creatinine kinase levels were comparable between the2groups(Table1).
A comparison of AE rates between the?rst year and the second year of the study period identi?ed local injection-site re-actions in12(2.5%)alirocumab-treated versus2(0.8%) ezetimibe-treated patients during the?rst year,compared with 1(0.2%)alirocumab-treated versus1(0.5%)ezetimibe-treated patient during the second year(Table2).Of the12injection-site reactions reported by alirocumab-treated patients during the ?rst year,11(92%)were of mild intensity(vs2[100%]in the ezetimibe group)and1(8.3%)was of moderate intensity (Table S3in the Supplement).During the second year,the single (100%)injection-site reaction reported in the alirocumab group was of mild intensity(vs1[100%]of severe intensity in the ezetimibe group,Table S3in the Supplement).
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Over the complete 2years of follow-up,there was no mean-ingful difference between treatment groups over the study period for ophthalmological events,neurological or neurocognitive disorders,hepatic disorders,or AEs related to diabetes or diabetic complications (Table 1,Table S4in the Supplement).Overall rates of speci?c AEs were similar in the alirocumab and ezetimibe groups for the ?rst and the second year (Table 2).In other AEs of interest,rates were similar in the ?rst and the second year of the study (Table 2).At least 2consecutive LDL-C values <25mg/dl were ob-served in 128(28%)patients in the alirocumab group (including 45[9.8%]patients with 2consecutive LDL-C values <15mg/dl),of whom 91(71%)reported at least 1AE after the ?rst LDL-C <25mg/dl value (Table 3).The median time to the ?rst calculated LDL-C value <25mg/dl and <15mg/dl was 12and 16weeks,respectively.Most patients were on 75mg Q2W alirocumab at the time of the ?rst LDL-C value <25mg/dl (90%)and <15mg/dl (88%).Of the 351alirocumab-treated patients with LDL-C ≥25mg/dl,288(82%)reported any AE (Table 3).The AE pro?le in patients with 2consecutive LDL-C values <25mg/dl was not notably dif-ferent from the overall population or from patients with LDL-C ≥25mg/dl,and no safety concerns were reported (Table 3).There were no injection-site reactions reported in these pa-tients:2(1.6%)patients with 2consecutive values of LDL-C <25mg/dl versus 7(2.0%)patients with LDL-C ≥25mg/dl who reported cataracts.One ezetimibe-treated patient had 2consecutive LDL-C <25mg/dl values (time to the ?rst
value
Figure 2.On-treatment analysis of (A)mean change in calculated LDL-C,and mean percent change from baseline in (B)Lp(a),(C)Apo B,(D)non–HDL-C,(E)HDL-C,and (F)triglycerides over 2years.*p <0.0001vs ezetimibe.Changes in lipoproteins versus study time points on treatment with alirocumab and ezetimibe.Values above and below the data points indicate the percentage reduction from baseline,with percentage differences indicated by the values next to the arrows.Apo =apolipoprotein;HDL-C =high-density lipoprotein cholesterol;LDL-C =low-density lipoprotein cholesterol;Lp(a)=lipoprotein(a);LS =least squares;SE =standard error.
934The American Journal of Cardiology (https://www.doczj.com/doc/cc16915121.html, )
of LDL-C <25mg/dl was 52weeks);this patient did not report any AEs.
Persistent ADA responses were observed in 1.3%(6of 454)of patients administered alirocumab versus 0.4%(1of 231)of patients administered ezetimibe,with median time of onset being 12and 52weeks,respectively (Table S5).The ?rst ADA response was observed in the ?rst year (weeks 0to 56)of treatment for all patients.ADA responses observed exhib-ited low titers,resolved over time,and had no clinical impact on either pharmacokinetics or safety of alirocumab.At least 1NAb response was observed in 1.5%(7of 454)of alirocumab-treated patients (mostly at single,isolated time points);no NAb responses were observed in ezetimibe-treated patients (Table S5).NAbs detected by immunoassays were transient and at isolated time points.Discussion
These data indicate that the ef?cacy and safety of alirocumab are maintained through 2years in high-risk pa-tients when administered in addition to MTD at 75mg Q2W,with potential increase to 150mg Q2W based on individual LDL-C responses at week 8.
Overall treatment adherence was high in both treatment groups and did not vary between the ?rst and the second year of the treatment period.In the on-treatment analysis,alirocumab resulted in sustained LDL-C reductions and goal achievement compared with ezetimibe,demonstrating supe-riority of treatment in patients at high CV risk not at LDL-C treatment goal.The slight decrease observed in ef?cacy at 2years compared with ef?cacy at 24weeks in the alirocumab-treated group was also observed in the ezetimibe-treated group.The changes in atherogenic lipid levels observed in this study are consistent with those in the overall ODYSSEY trials.9Each LDL particle contains a molecule of Apo B.Uptake of LDL-C and other Apo B-containing lipids occurs via the LDL receptor.PCSK9promotes degradation of the LDL recep-tor,hence alirocumab-mediated inhibition of PCSK9increases LDL receptor availability resulting in reduced levels of not only LDL-C but also Apo B.10Non–HDL-C (total
Table 1
Frequency of adverse events from baseline to end of study (safety population)V ariable
Alirocumab (n =479)
Ezetimibe (n =241)Any AE
391(81.6%)198(82.2%)Treatment–emergent SAE 124(25.9%)60(24.9%)AE leading to death
6(1.3%)6(2.5%)AE leading to permanent treatment discontinuation 44(9.2%)19(7.9%)AEs of special interest *
Local injection-site reactions 13(2.7%)3(1.2%)General allergic reactions 38(7.9%)17(7.1%)Hemolytic anemia 0
Neurological events
19(4.0%)11(4.6%)Neurocognitive disorders 6(1.3%)5(2.1%)Ophthalmological events 9(1.9%)4(1.7%)Hepatic disorders
19(4.0%)11(4.6%)AEs related to diabetes mellitus or diabetic complications 35(7.3%)19(7.9%)Patients with diabetes at baseline n =148n =77Any AE
17(11.5%)10(13.0%)Patients without diabetes at baseline n =331n =164Any AE 18(5.4%)9(5.5%)MACE ?
23(4.8%)8(3.3%)CHD death 4(0.8%)2(0.8%)Non-fatal MI 16(3.3%)5(2.1%)Ischemic stroke
2(0.4%)1(0.4%)Unstable angina requiring hospitalization
1(0.2%)1(0.4%)Ischemia driven coronary revascularization procedure ?21(4.4%)7(2.9%)Laboratory parameters §
Alanine aminotransferase >3x ULN 10/470(2.1%)2/240(0.8%)Aspartate aminotransferase >3x ULN 11/470(2.3%)1/240(0.4%)Creatine kinase >3x ULN
17/467(3.6%)
8/236(3.4%)
n (%)=number and percentage of patients with at least 1AE.
*Certain AEs were grouped as AEs of special interest (prespeci?ed in the ODYSSEY phase 3study protocols),based on identi?ed,potential,and theo-retical risks for the new drug class collected during the clinical trial program.AEs related to diabetes mellitus or diabetic complications are regardless of baseline status.Based on standard or custom Medical Dictionary of Regulatory Activities queries.?
Number and percentage of patients with at least 1MACE (coronary heart disease death,nonfatal MI,ischemic stroke,or unstable angina requiring hospitalization).?
Ischemia-driven coronary revascularization procedure related to coronary artery bypass grafting and percutaneous coronary intervention if the reason for procedure is new episode of ischemia occurring after randomization.§
The denominator for each parameter within a treatment group is the number of patients who had that parameter assessed after baseline (not missing)during the AE period.
AE =adverse event;CHD =coronary heart disease;MACE =major adverse cardiac event;MI =myocardial infarction;SAE =serious adverse event;ULN =upper limit of normal.
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Preventive Cardiology/Long-Term Safety and Ef?cacy of Alirocumab
cholesterol minus HDL-C)is largely composed of LDL-C, and hence is also reduced with alirocumab.Studies also in-dicate that the increase in LDL receptors observed with alirocumab treatment may increase catabolism of Lp(a).11,12 However,as statins reduce LDL-C but have little effect on Lp(a),other evidence suggests that Lp(a)reductions from PCSK9inhibition may also be mediated by pathways not in-volving the LDL receptor.13,14An increase in HDL-C observed with alirocumab may be attributed to decreased LDL avail-able to interact with cholesterol.15,16
Overall AEs at2years were mostly comparable between the2treatment groups,except for injection-site reactions and allergic reactions.Glycemic control over2years of treat-ment in all individuals with and without diabetes from COMBO II has been analyzed in a separate study.17Median fasting glucose and glycated hemoglobin values up to2years in those with and without diabetes were comparable between treatment groups.17The slightly increased rate of injection-site reactions in alirocumab-treated patients was seen only in the?rst year of the study,indicating that these reactions occur early during exposure.The decreased rate of injection-site reactions in the second compared with the?rst year was unlikely to be due to treatment discontinuation.The AE rates seen in patients with2consecutive calculated LDL-C values of<25mg/dl were similar to the overall alirocumab-treated population.
Administration of alirocumab75mg Q2W or75mg in-creased to150mg Q2W as an add-on therapy over2years
Table2
Frequency of adverse events in patients who received alirocumab versus ezetimibe reported at?rst(weeks0to56)and second year(weeks56to112) V ariable Alirocumab Ezetimibe
Weeks0–56 (n=479)Weeks56–112
(n=411)
Weeks0–56
(n=241)
Weeks56–112
(n=209)
Any AE343(71.6%)249(60.6%)166(68.9%)129(61.7%) Treatment–emergent SAE87(18.2%)55(13.4%)40(16.6%)30(14.4%) AE leading to death2(0.4%)4(1.0%)6(2.5%)2(1.0%) AE leading to permanent treatment discontinuation39(8.1%)5(1.2%)15(6.2%)5(2.4%) AEs occurring in≥5%of patients in any of the groups
Infections and infestations128(26.7%)75(18.2%)61(25.3%)67(32.1%) Upper respiratory tract infection31(6.5%)14(3.4%)13(5.4%)6(2.9%) Musculoskeletal and connective tissue disorders93(19.4%)64(15.6%)41(17.0%)25(12.0%) Myalgia21(4.4%)6(1.5%)13(5.4%)0 Nervous system disorders78(16.3%)39(9.5%)38(15.8%)24(11.5%) Dizziness21(4.4%)9(2.2%)13(5.4%)6(2.9%) Gastrointestinal disorders76(15.9%)37(9.0%)30(12.4%)31(14.8%) Injury,poisoning,and procedural complications58(12.1%)46(11.2%)34(14.1%)20(9.6%) Accidental overdose29(6.1%)22(5.4%)17(7.1%)5(2.4%) Cardiac disorders58(12.1%)26(6.3%)28(11.6%)21(10.0%) General disorders and administration site conditions56(11.7%)24(5.8%)25(10.4%)13(6.2%) Respiratory,thoracic,and mediastinal disorders43(9.0%)20(4.9%)21(8.7%)16(7.7%) Investigations38(7.9%)20(4.9%)23(9.5%)7(3.3%) Skin and subcutaneous tissue disorders34(7.1%)19(4.6%)15(6.2%)4(1.9%) V ascular disorders34(7.1%)27(6.6%)21(8.7%)14(6.7%) Metabolism and nutrition disorders32(6.7%)19(4.6%)18(7.5%)10(4.8%) Psychiatric disorders21(4.4%)9(2.2%)12(5.0%)4(1.9%) Eye disorders21(4.4%)10(2.4%)6(2.5%)11(5.3%) Renal and urinary disorders20(4.2%)17(4.1%)12(5.0%)8(3.8%) AEs of special interest*
General allergic reaction29(6.1%)13(3.2%)12(5.0%)5(2.4%) AEs related to diabetes mellitus or diabetic complications?24(5.0%)13(3.2%)10(4.1%)9(4.3%) Neurological13(2.7%)7(1.7%)6(2.5%)5(2.4%) Local injection-site reactions12(2.5%)1(0.2%)2(0.8%)1(0.5%) Hepatic disorders11(2.3%)9(2.2%)7(2.9%)6(2.9%) Ophthalmological7(1.5%)2(0.5%)1(0.4%)3(1.4%) Neurocognitive disorder3(0.6%)4(1.0%)4(1.7%)1(0.5%) Weeks56to112included double-blind treatment up to week104plus an8-week follow-up.To have equal time periods for comparison,AEs were ana-lyzed for weeks0to56and weeks56to112.If a patient had an event once in weeks0to56and once in weeks56to112,the2events were recorded separately in the respective time period they occurred.
*Certain AEs were grouped as AEs of special interest(prespeci?ed in the phase3study protocols),based on identi?ed,potential,and theoretical risks for the new drug class collected during the clinical trial program.These included local injection-site reactions,general allergic events,neurological events,hepatic disorders,and ophthalmological events.Other prede?ned categories,including AEs related to neurocognitive disorders and diabetes mellitus,were analyzed in the same way as the other AEs of interest,but not speci?cally de?ned as AEs of special interest in the protocols.AEs related to diabetes mellitus or dia-betic complications are regardless of baseline status.Based on standard or custom Medical Dictionary of Regulatory Activities queries.
?AEs related to diabetes mellitus or diabetic complications are regardless of baseline status.
AE=adverse event;SAE=serious adverse event.
936The American Journal of Cardiology(https://www.doczj.com/doc/cc16915121.html,)
was associated with low levels of immunogenicity.NAb re-sponses identi?ed by immunoassays were transient and observed in 7alirocumab-treated patients.These responses do not necessarily impact clinical ef?cacy;however,a robust analysis of the ef?cacy of alirocumab by ADA status in this study was not possible because of the low patient numbers.In a pooled analysis of 10ODYSSEY Phase 3trials with 4747patients,including the COMBO II study,ADA and NAb re-sponses occurred at a low rate and were transient,occurring at single time points.8In the overall ODYSSEY program,mean reductions in LDL-C were maintained over time in patients with persistent and NAb responses.8Overall,the results of the post hoc safety analysis up to 2years reported here are comparable with those reported previously up to 1.5years (78weeks)in the ODYSSEY LONG TERM study.1The similar safety pro?le of alirocumab-and ezetimibe-treated pa-tients in the later time period of the study should be interpreted cautiously,as patients with AEs reported in the ?rst year may have discontinued treatment.This study was not powered for analysis of CV events.Pooled post hoc analysis from the ODYSSEY program indicated a 24%risk reduction in major adverse CV events per 39mg/dl lower LDL-C level (hazard
ratio 0.79,95%CI 0.63to 0.91).18In this study,LDL-C was reduced by 53mg/dl with alirocumab at 2years.Recent clini-cal outcomes results with other PCSK9inhibitors have yielded promising results.6,19The ongoing ODYSSEY OUTCOMES study has randomized approximately 18,000patients to alirocumab or placebo to evaluate the effect of treatment on major adverse CV events.20These end-of-study data from COMBO II provide important information for clinicians and patients on the ef?cacy and safety of alirocumab co-administered with MTD.Disclosures
Dr.El Shahawy reports research support from AstraZeneca,Amgen,Bristol-Myers Squibb,Boehringer Ingelheim,Eli Lilly &Company,P?zer,Regeneron Pharmaceuticals,Inc.,Sano?,Tasly,and the National Institutes of Health;and has participated in speaker’s bureau for Amgen,Bristol-Myers Squibb,Novartis,P?zer,Regeneron Pharmaceuticals,Inc.,and Sano?.
Dr.Cannon has received grant support from Accumetrics,Arisaph,AstraZeneca,Boehringer Ingelheim,CSL Behring,
Table 3
Frequency of adverse events in alirocumab-treated patients with 2consecutive calculated low-density lipoprotein cholesterol values <25mg/dl and with low-density lipoprotein cholesterol values ≥25mg/dl (safety population)V ariable
Alirocumab 2LDL-C <25mg/dL (n =128)
Alirocumab LDL-C ≥25mg/dL (n =351)
Any AE
91(71.1%)288(82.1%)Treatment–emergent SAE 27(21.1%)92(26.2%)AE leading to death
6(1.7%)AE leading to permanent treatment discontinuation 6(4.7%)38(10.8%)AEs occurring in ≥5%of patients Infections and infestations 39(30.5%)124(35.3%)Nasopharyngitis
8(6.3%)11(3.1%)Upper respiratory tract infection
6(4.7%)34(9.7%)Musculoskeletal and connective tissue disorders 29(22.7%)107(30.5%)Arthralgia 5(3.9%)20(5.7%)Myalgia
4(3.1%)21(6.0%)Gastrointestinal disorders 25(19.5%)74(21.1%)Nervous system disorders 18(14.1%)84(23.9%)Dizziness 5(3.9%)23(6.6%)Headache
4(3.1%)25(7.1%)Cardiac disorders
16(12.5%)55(15.7%)Injury,poisoning,and procedural complications 15(11.7%)77(21.9%)Accidental overdose 8(6.3%)36(10.3%)Investigations
14(10.9%)38(10.8%)Metabolism and nutrition disorders 11(8.6%)34(9.7%)Diabetes mellitus
3(2.3%)7(2.0%)General disorders and administration site conditions 11(8.6%)55(15.7%)Skin and subcutaneous tissue disorders 11(8.6%)30(8.5%)V ascular disorders 10(7.8%)44(12.5%)Hypertension
6(4.7%)25(7.1%)Respiratory,thoracic,and mediastinal disorders 10(7.8%)45(12.8%)Renal and urinary disorders
9(7.0%)24(6.8%)Reproductive system and breast disorders 5(3.9%)18(5.1%)Psychiatric disorders 5(3.9%)23(6.6%)Eye disorders
3(2.3%)
27(7.7%)
n (%)=number and percentage of patients with at least 1AE.
Only AEs that occurred,worsened,or became serious the day or after the ?rst of the 2consecutive LDL-C <25mg/dl are considered for alirocumab 2LDL-C <25mg/dl group.Values are considered consecutive if spaced out by at least 21days.
Alirocumab LDL-C ≥25mg/dl group:alirocumab patients without 2consecutive LDL-C <25mg/dl.AE =adverse event;LDL-C =low-density lipoprotein cholesterol;SAE =serious adverse event.
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Preventive Cardiology/Long-Term Safety and Ef?cacy of Alirocumab
Essentials,GlaxoSmithKline,Janssen,Merck,Regeneron Phar-maceuticals,Inc.,Sano?,and Takeda;and consultant/ advisory board fees from Bristol-Myers Squibb,LipoMedix, and P?zer.
Dr.Blom has received grants for conducting clinical trials from Sano?-Aventis,Regeneron Pharmaceuticals,Inc., Novartis,Eli Lilly&Company,Amgen,and Aegerion;hono-raria for lectures from Sano?-Aventis,Regeneron Pharmaceuticals,Inc.,Aegerion,Amgen,AstraZeneca,MSD, P?zer,Servier,and Unilever;advisory board fees from Sano?-Aventis,Aegerion,Amgen,AstraZeneca,and MSD;travel assistance from Amgen and Aegerion;a fee for chairing a steer-ing committee from Aegerion;a consultancy fee from Gemphire;and non?nancial support(editorial assistance and statistical analysis)from Sano?-Aventis and Regeneron Phar-maceuticals,Inc.
Dr.McKenney reports no disclosures.
Dr.Cariou reports personal fees from Sano?,during the conduct of the study;and personal fees from Amgen,Eli Lilly &Company,Gen?t,MSD,Novo Nordisk,Pierre Fabre, AstraZeneca,Sano?,and Regeneron Pharmaceuticals,Inc., outside the submitted work.
Mr.Lecorps and Dr.Chaudhari report they are employ-ees and stockholders of Sano?.
Dr.Pordy reports he is an employee and stockholder of Regeneron Pharmaceuticals,Inc.
Dr.Colhoun has received research support from P?zer and Sano?,and reports grants,personal fees,and non?nancial support from Sano?and Regeneron Pharmaceuticals,Inc., during the conduct of the study;grants,personal fees,and non?nancial support from Eli Lilly&Company,grants and other support from Roche Pharmaceuticals,grants from P?zer, Boehringer Ingelheim,and AstraZeneca LP,and other support from Bayer,outside the submitted work. Acknowledgments:The authors would like to thank the pa-tients,their families,and all investigators involved in this study. The following people from the study sponsors provided edi-torial comments on the manuscript:Jay Edelberg,Tu Nyugen, Michael Howard,and L.Veronica Lee(Sano?),and William J.Sasiela,Rita Samuel,and Carol Hudson(Regeneron Phar-maceuticals,Inc.).Statistical analyses were performed by Guillaume Lecorps,Sano?.Dr.El Shahawy MD had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analy-sis.Medical writing support under the direction of the authors was provided Rob Campbell,PhD,and Aparna Shetty,PhD, of Prime(Knutsford,UK),supported by Sano?and Regeneron Pharmaceuticals,Inc.,according to Good Publication Prac-tice guidelines(Link).The sponsors were involved in the study design,collection,analysis and interpretation of data,as well as data checking of information provided in the article.The authors were responsible for all content and editorial deci-sions and received no honoraria related to the development of this publication.
Supplementary Data
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The prerequisite for vigorously developing our productivity is that we must be responsible for the safety of our company and our own lives. （安全管理） 单位：___________________ 姓名：___________________ 日期：___________________ 挖土安全操作规程(新编版)
挖土安全操作规程(新编版)导语：建立和健全我们的现代企业制度，是指引我们生产劳动的方向。而大力发展我们生产力的前提，是我们必须对我们企业和我们自己的生命安全负责。可用于实体印刷或电子存档（使用前请详细阅读条款）。 1挖土前根据安全技术交底了解地下管线、人防及其他构筑物情况和具体位置。地下构筑物外露时，必须进行加固保护。作业过程中应避开管线和构筑物。在现场电力、通信电缆2m范围内和现场燃气、热力、给排水等管道1m范围内挖土时，必须在主管单位人员监护下采取人工开挖。 2开挖槽、坑、沟深度超过1.5m，必须根据土质和深度情况按安全技术交底放坡或加可靠支撑，遇边坡不稳、有坍塌危险征兆时，必须立即撤离现场。并及时报告施工负责人，采取安全可靠排险措施后，方可继续挖土。 3槽、坑、沟必须设置人员上下坡道或安全梯。严禁攀登固壁支撑上下，或直接从沟；坑边壁上挖洞攀登爬上或跳下。间歇时，不得在槽、坑坡脚下休息。 4挖土过程中遇有古墓、地下管道、电缆或其他不能辨认的异物和液体、气体时，应立即停止作业，并报告施工负责人，待查明处理后，
实验室岗位安全操作规程 1、在实验室工作当中存在化学灼伤、气体中毒、火灾触电、机械伤害等风险。 2、实验人员在实验室内必须穿戴工作服装，取样人员必须佩戴好相应的劳保用品与安全防护用具。 3、所有药品、标样、溶液都应有标签，绝对不要在容器内装入与标签不相符的物品。 4、不准穿拖鞋进入实验室，注意保持实验室的清洁卫生。 5、有毒、腐蚀、易燃、易爆的物品应妥善保管。贮存和使用应遵守?化学危险物品安全管理条例?。 6、实验室内严禁吸烟、饮水、进食。 7、开启易挥发液体试剂之前，先将试剂瓶放在自来水流中冷却几分钟，开启时，瓶口不要对人，最好在通风厨中进行。 8、易燃溶剂加热时，必须在水浴或沙浴中进行。 9、装过强腐蚀性、可燃性、有毒或易燃物品的器皿必须由使用者亲自洗净。 10、实验时若发现仪器设备出现故障或异常情况（如：有异味、冒烟等）时，应立即关闭电源开关，拨掉电源插头，并及时向实验室管理人员报告。 11、取下正在沸腾的溶液时，应用瓶夹摇动后取下以免溅出伤人。 12、玻璃棒、玻璃管、温度计等插入或拔出胶管时，均应垫有棉布且不可强行插入或拔出，以免折断刺伤人。
13、实验完毕，要关闭设备的电源、关好通风橱、整理好仪器设备，并打扫卫生。 14、配制药品或试验中能放出HCN、NO2、H2S、SO2、NH3及其它有毒和腐蚀性气体时，应在通风厨中进行，并带好必要的劳保用品。 15、实验室内应备有急救药品，消防器材和劳保用品。 16、化验室内应保持空气流通，环境清洁、安静。 17、易燃性气体不可与有助燃性的气体放到一个气瓶间，气瓶间内一定要有相应的防爆防倾设施。 18、样品的取样、接受、贮存和处置等要符合国家和公司的相关规定。 19、对实验产生的废液、废油、废物要分类存放并定期处置，禁止随意倾倒和储存。 20、实验室使用及存储的化学药剂或化学危险品都应备有相对应的化学品安全技术说明书（即MSDS），包括电子版和纸质版，并存放于实验室工作人员易于查找阅读的地方。同时实验室工作人员在使用化学药剂（特别是危险化学品）之前要对MSDS进行阅读学习，了解其危险特性及应急措施。 21、化学烧伤事故应急措施：当浓酸溅到眼睛或皮肤上时，应立即用大量清水冲洗，再用0.5%的碳酸氢钠溶液清洗；当强碱溅到眼睛或皮服上时，应迅速用大量清水冲洗再用2%的稀硼酸溶液清洗眼睛或用1%的醋酸溶液清洗皮肤。 当酸和碱滴溅到眼睛或皮肤上时，除经过上述处理外，还应马上送往医院进行救护。
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挖土安全操作规程(新版) 1挖土前根据安全技术交底了解地下管线、人防及其他构筑物情况和具体位置。地下构筑物外露时，必须进行加固保护。作业过程中应避开管线和构筑物。在现场电力、通信电缆2m范围内和现场燃气、热力、给排水等管道1m范围内挖土时，必须在主管单位人员监护下采取人工开挖。 2开挖槽、坑、沟深度超过1.5m，必须根据土质和深度情况按安全技术交底放坡或加可靠支撑，遇边坡不稳、有坍塌危险征兆时，必须立即撤离现场。并及时报告施工负责人，采取安全可靠排险措施后，方可继续挖土。 3槽、坑、沟必须设置人员上下坡道或安全梯。严禁攀登固壁支撑上下，或直接从沟；坑边壁上挖洞攀登爬上或跳下。间歇时，不得在槽、坑坡脚下休息。
4挖土过程中遇有古墓、地下管道、电缆或其他不能辨认的异物和液体、气体时，应立即停止作业，并报告施工负责人，待查明处理后，再继续挖土。 5槽、坑、沟边1m以内不得堆土、堆料、停置机具。堆土高度不得超过1.5m。槽、坑、沟与建筑物、构筑物的距离不得小于1.5m。开挖深度超过2m时，必须在周边设两道牢固护身栏杆，并立挂密目安全网。 6人工开挖土方，两人横向间距不得小于2m，纵向间距不得小于3m。严禁掏洞挖土，搜底挖槽。 7钢钎破冻土、坚硬土时，扶钎人应站在打锤人侧面用长把夹具扶钎，打锤范围内不得有其他人停留。锤顶应平整，锤头应安装牢固。钎子应直且不得有飞刺。打锤人不得戴手套。 8从槽、坑、沟中吊运送土至地面时，绳索、滑轮、钩子、箩筐等垂直运输设备、工具应完好牢固。起吊、垂直运送时，下方不得站人。 9配合机械挖土清理槽底作业时，严禁进入铲斗回转半径范围。
一级建造师《建设工程经济》计算公式汇总 1、等额支付系列的终值、现值、资金回收和偿债基金计算 等额支付系列现金流量序列是连续的，且数额相等，即： ） ，，，，常数（n t A A t 321 ①终值计算（即已知A 求F ） i i A F n 11 ）（ ②现值计算（即已知A 求P ） n n n i i i A i F P ）（）（） （ 1111 ③资金回收计算（已知P 求A ） 111 n n i i i P A ）（） （ ④偿债基金计算（已知F 求A ） 1 1 n i i F A ）（ 2、有效利率的计算 包括计息周期有效利率和年有效利率两种情况。 （2）年有效利率，即年实际利率。 年初资金P ，名义利率为r ，一年内计息m 次，则计息周期利率为 m r i 。根据一次支付终值公式可得该年的本利和F ，即： m m r P F 1 根据利息的定义可得该年的利息I 为： 111m m m r P P m r P I 再根据利率的定义可得该年的实际利率，即有效利率i eFF 为： 11i eff m m r P I 3、财务净现值 t c t n t i CO CI FNPV 10 式中 FNPV ——财务净现值； （CI-CO ）t ——第t 年的净现金流量（应注意“＋”、“-”号）； i c ——基准收益率； n ——方案计算期。 4、财务内部收益率（FIRR ——Financial lnternaI Rate oF Return ） 其实质就是使投资方案在计算期内各年净现金流量的现值累计等于零时的折现率。其数学表达式为：
t t n t FIRR CO CI FIRR FNPV 10 式中 FIRR ——财务内部收益率。 5、投资收益率指标的计算 是投资方案达到设计生产能力后一个正常生产年份的年净收益总额（不是年销售收入）与方案投资总额（包括建设投资、建设期贷款利息、流动资金等）的比率： %100 I A R 式中 R ——投资收益率； A ——年净收益额或年平均净收益额； I ——总投资 6、总投资收益率 总投资收益率（ROI ）表示总投资的盈利水平 %100 TI EBIT ROI 式中 EBIT-----技术方案正常年份的年息税前利润或运营期内平均息税前利润； TI------技术方案总投资包括建设投资、建设期利息和全部流动资金。 7、资本金净利润率（ROE ） 技术方案资本金净利润率（ROE ）表示技术方案盈利水平 %100 EC NP ROE 式中 NP----技术方案正常年份的年净利润或运营期内年平均净利润， 净利润＝利润总额-所得税 EC----技术方案资本金 8、静态投资回收期 ·当项目建成投产后各年的净收益（即净现金流量）均相同时，静态投资回收期计算： A I P t 式中 I ——总投资； A ——每年的净收益。 ·当项目建成投产后各年的净收益不相同时，静态投资回收期计算： 流量 出现正值年份的净现金的绝对值 上一年累计净现金流量现正值的年份数累计净现金流量开始出 1－ t P 9、借款偿还期 余额 盈余当年可用于还款的盈余当年应偿还借款额 的年份数借款偿还开始出现盈余 1－d P 10、利息备付率 利息备付率＝息税前利润/计入总成本费用的应付利息。 式中：息税前利润——即利润总额与计入总成本费用的利息费用之和（不含折旧、摊销费 11、偿债备付率 偿债备付率＝（息税前利润加折旧和摊销-企业所得税）/应还本付息的金额 式中：应还本付息的资金——包括当期还贷款本金额及计入总成本费用的全部利息； 息税前利润加折旧和摊销-企业所得税＝净利润+折旧+摊销+利息 12、总成本 C ＝C F ＋C u ×Q C ：总成本；C F ：固定成本；C u ：单位产品变动成本；Q ：产销量 量本利模型
实验室安全操作规范 一、穿着规定 1、进入实验室，必须穿戴工作服。 2、进行危害物质、挥发性有机溶机、特定化学物质或其它毒性化学物质等化学药品及生物样品操作，必须要穿戴防护具（例如防护手套、口罩、防毒面具等）。 3、进行实验中，严禁戴隐形眼镜（防止化学药剂溅入眼内而腐蚀灼伤眼睛）。 4、需将长发及松散衣服妥善固定，且实验室内不得穿拖鞋。 5、操作高温（低温）实验，必须戴防高温（低温）手套。 6、实验服严禁穿回办公区。 二、饮食规定 1、严禁在实验室内吃东西。 2、食物禁止储藏在实验室的冰箱或储藏柜内。 三、试剂存储及操作相关规定 1、未进检测室时对实验过程进行预习，掌握操作过程及原理，弄清所有检测仪器及试剂的特性。估计可能发生危险的实验，操作时注意防范。 2、实验开始前检查仪器是否完好，装置是否正确稳妥。 3、实验进行时应经常注意仪器是否漏液、漏气、碎裂，反应是否正常等。 4、操作危险性试剂时，必须严格遵守操作守则，严禁自行更改实验流程。 5、使用试剂时，要首先确认容器上标示的名称是否为需要的实验试剂。确认药品是否为危害品，有无警告标识。 6、使用挥发性有机溶剂、强酸强碱、腐蚀性试剂、有毒试剂等必须在通风橱内进行操作。 7、有机溶剂、固体化学药品、酸性和碱性化合物均需分开存放，挥发性的化学药品必需放于通风良好的试剂柜内保存。 8、避免独自一人在实验室做危险实验。 9、做危险性实验时必须经领导批准，有两人以上在场方可进行，节假日和夜间严禁做危险性实验。 10、做有危害性气体的实验时，必须在通风橱里进行。 11、进行实验操作时（蜗旋、挥干、吹干等），严禁容器口对着人。 12、绝对不允许任意混合各种试剂以免发生危险。不能用手接触药品，不要用鼻子去闻试剂的气味，不得品尝任何试剂的味道。 13、检测剩余的实验试剂不得随意丢弃或带出实验室，放回指定容器或按规定处理。 14、实验操作完毕必须仔细认真清洗或擦拭可重复使用的实验器材，放置于规定位置。 四、用电相关安全规定 1、实验室内电气设备的安装和使用管理，必须符合安全用电要求，大功率实验设备用电必须使用专线，严禁与照明线共用，谨防因超负荷用电着火。 2、实验室内不准乱拉乱接电线。 3、实验室内的用电线路和配电盘、板、箱、柜等装置及线路系统中的各种开关、插座、插头等均应经常保持完好可用状态，空气开关功率必须与线路允许的容量相匹配。室内照明器具都要经常保持稳固可用状态。 4、实验室内仪器设备凡本身要求安全接地的，必须接地；要定期检查线路。 5、实验室内不得使用明火取暖，严禁抽烟。 6、手上有水或潮湿的，禁止接触电器用品或电器设备。 7、实验室内的鉴定人员必须掌握本室仪器、设备的性能和操作方法，严格按照规程操作。
安规基础知识 灯具安规基础知识 一、灯具防护等级分类 灯具的分类方法很多，依照安全防护等级可以分为0类、I类、II类、III类。 1、0类灯具 工作电压是高压，防触电保护采用基本绝缘，而无其他防触电保护措施的灯具。此类灯具安全性能较差，目前欧美国家已不允许生产销售。0类灯具无符号标识。 特征：高压、无接地线、单层绝缘。 2、I类灯具 工作电压是高压，防触电保护采用单层绝缘基本绝缘外，还采用接地作为防触电保护的灯具。 I类灯具无符号标识，其内部可以包含有II类结构，即I类灯具内部分电气结构可以采用双绝缘的方式。 特征：高压、有接地、单层绝缘。 3、II类灯具 工作电压是高压，防触电保护采用双层绝缘的灯具。 II类灯具用符号标识，其内部可以包含有III类结构。特征：高压、无接地、双层绝缘。 4、III类灯具 工作电压是安全电压的灯具。 III类灯具用符号 标识。 特征：安全电压供电。 二、绝缘 1、基本绝缘 基本绝缘是灯具中用于带电体防触电保护最基本的绝缘，基本绝缘应能通过2U+1000V~的高压测试。 灯具的结构应能保障正常非拆卸状态下基本绝缘不能被手（测试手）触摸到。 2、补充绝缘 在基本绝缘基础上增加的一层绝缘，用于当基本绝缘失效时的防触电 保护，补充绝缘必须要固定。补充绝缘应能通过2U+1750V~的高压测试。 3、双层绝缘 基本绝缘、补充绝缘同时合并在一起称为双层绝缘，双层绝缘也称双绝缘、双重绝缘。双层绝缘应能通过4U+2750V~的高压测试。 4、单层绝缘 单层绝缘就是指基本绝缘，其各方面要求与基本绝缘相同。 5、加强绝缘 加强绝缘也叫增强绝缘，其绝缘效果与双重绝缘相当的一种单一绝缘体。从其结构来看一般仅有一层，或由不能单独分割测量的多层组成。 加强绝缘与双层绝缘一样要能通过4U+2750V~的高压测试。 三、安全距离 1、爬电距离
人工挖土安全操作规程示 范文本 In The Actual Work Production Management, In Order To Ensure The Smooth Progress Of The Process, And Consider The Relationship Between Each Link, The Specific Requirements Of Each Link To Achieve Risk Control And Planning 某某管理中心 XX年XX月
人工挖土安全操作规程示范文本 使用指引：此操作规程资料应用在实际工作生产管理中为了保障过程顺利推进，同时考虑各个环节之间的关系，每个环节实现的具体要求而进行的风险控制与规划，并将危害降低到最小，文档经过下载可进行自定义修改，请根据实际需求进行调整与使用。 1.人工挖孔桩施工适用于桩径800～2000mm、桩深 不超过25m的桩。 2.从事挖孔桩的作业人员必须视力、嗅觉、听觉、心 脏、血压正常，必须经过安全技术培训，考核合格方可上 岗。 3.人工挖孔桩施工前，应根据桩的直径、桩深、土质、 现场环境等状况进行混凝土护壁结构的设计，编制施工方 案和相应的安全技术措施，并经企业负责人和技术负责人 签字批准。 4.施工前，总承包的施工企业应和具有资质的分包施工 企业签订专业分包合同，合同中必须规定双方的安全责 任。
5.人工挖孔桩施工前应对现场环境进行调查，掌握以下情况： ⑴地下管线位置、埋深和现况； ⑵地下构筑物（人防、化粪池、渗水池、坟墓等）的位置、埋深和现况； ⑶施工现场周围建（构）筑物、交通、地表排水、振动源等情况； ⑷高压电气影响范围。 6.人工挖孔桩施工前，工程项目经理部的主管施工技术人员必须向承担施工的专业分包负责人进行安全技术交底并形成文件。交底内容应包括施工程序、安全技术要求、现况地下管线和设施情况、周围环境和现场防护要求等。 7.人工挖孔作业前，专业分包负责人必须向全体作业人员进行详细的安全技术交底，并形成文件。 8.施工前应检查施工物资准备情况，确认符合要求，并
编号：SM-ZD-85177 实验室安全标准操作规程Through the process agreement to achieve a unified action policy for different people, so as to coordinate action, reduce blindness, and make the work orderly. 编制：____________________ 审核：____________________ 批准：____________________ 本文档下载后可任意修改
实验室安全标准操作规程 简介：该规程资料适用于公司或组织通过合理化地制定计划，达成上下级或不同的人员之间形成统一的行动方针，明确执行目标，工作内容，执行方式，执行进度，从而使整体计划目标统一，行动协调，过程有条不紊。文档可直接下载或修改，使用时请详细阅读内容。 1职责 1.1实验室主任对安全全面负责。经常进行安全督察，组织安全检查，负责处理安全事故。 1.2实验员负责水、电线路、消防器材的配置和设施安全检查。 1.3各科实验老师负责本科的化学药品、水电气、门窗的安全。 1.4实验员负责试剂、药品，特别是有毒有害，易燃、易爆物质的管理。 2. 工作程序 2.1 安全操作规范 2.1.1检测人员在工作中要严格按照操作规程，杜绝一切违章操作，发现异常情况立即停止工作，并及时登记报告。 2.1.2禁止用嘴、鼻直接接触试剂。使用易挥发、腐蚀性
强、有毒物质必须带防护手套，并在通风橱内进行，中途不许离岗。 2.1.3在进行加热、加压、蒸馏等操作时，操作人员不得随意离开现场，若因故须暂时离开，必须委托他人照看或关闭电源。 2.1.4各种安全设施不许随意拆卸搬动、挪作他用，保证其完好及功能正常。 2.1.5操作人员要熟悉所使用的仪器设备性能和维护知识，熟悉水、电、燃气、气压钢瓶的使用常识及性能，遵守安全使用规则，精心操作。 2.2 有毒有害物质的管理 2.2.1化学试剂、药品中凡属易燃易爆，有毒(特别是剧毒物品)、易挥发产生有害气体的均应列为危险物品，严格分类，加强管理，专人负责。 2.2.2建立详细帐目，帐、物、卡相符，专人限量采购，入库检查。 2.2.3危险物品、易燃易爆物品单独存放，有毒物品放入专用加锁铁柜内，注意通风。
工作行为规范系列 人工挖土安全要求规程（标准、完整、实用、可修改）
编号：FS-QG-78734人工挖土安全要求规程 Manual excavation safety requirements 说明：为规范化、制度化和统一化作业行为，使人员管理工作有章可循，提高工作效率和责任感、归属感，特此编写。 1.新工人必须参加入场安全教育，考试合格后方可上岗。 2.在从事挖土作业前必须熟悉作业内容、作业环境，对使用的工具要进行检修，不牢固者不得使用;作业时必须执行安全技术交底，服从带班人员指挥。 3.配合其他专业工种人员作业时，必须服从该专业工种人员的指挥。 4.作业时必须根据作业要求，佩戴防护用品，施工现场不得穿拖鞋。 5.作业时必须遵守劳动纪律。不得擅自动用各种机电设备。 6.挖土前应按安全技术交底要求了解地下管线、人防及其他构筑物情况，按要求坑探，掌握构筑物的具体位置。地下构筑物外露时，应按交底要求进行加固保护。作业中应避
开管线和构筑物。在现场电力、通讯电缆2m范围内和现场燃气、热力、给排水等管道1m范围内挖土时，必须在主管单位人员的监护下采取人工开挖。 7.开挖槽(坑、沟)深度超过1.5m时必须根据土质和开挖深度情况按技术交底要求放坡、支撑或护壁。遇边坡不稳、有坍塌危险征兆时，必须立即撤离现场。并报告有关负责人，经过安全处理后，方可继续施工。 8.槽、坑、沟边上口边1m以内，不得来回上人走动，不得堆放任何物、料、机具或杂物，堆±高度不得超过1.5m。槽、坑、沟与建筑物、构筑物之间距离不得小于1.5m。堆土不得遮压检查井、消防井等设施。 9.开挖深度超过2m时，必须在周边设置牢固的安全防护栏，并立挂密目安全网。槽深大于2.5m时，应分层挖土，层高不得超过2m，层间应设平台，平台宽度不得小于0.5m。作业时两人横向间距不得小于2m，纵向间距不得小于3m。严禁掏洞挖土、搜底扩槽，严禁在槽内或坑坡脚下休息。 10.槽、坑、沟根据情况必须设置上下坡道或安全梯。进出上、下沟槽必须走马道、安全梯。马道、安全梯间距不宜
、平整场地：建筑物场地厚度在±30cm 以内的挖、填、运、找平。 1、平整场地计算规则 (1)清单规则：按设计图示尺寸以建筑物首层面积计算。 (2 )定额规则：按设计图示尺寸以建筑物外墙外边线每边各加2 米以平方米面积计算。 2、平整场地计算公式 S= (A+4 ) X ( B+4 ) =S 底+2L 外+16 式中：S———平整场地工程量；A———建筑物长度方向外墙外边线长度；B———建筑物宽度方向外墙外边线长度；S 底———建筑物底层建筑面积；L 外———建筑物外墙外边线周长。 该公式适用于任何由矩形组成的建筑物或构筑物的场地平整工程量计算。 二、基础土方开挖计算 开挖土方计算规则 ( 1 )、清单规则：挖基础土方按设计图示尺寸以基础垫层底面积乘挖土深度计算。 ( 2)、定额规则：人工或机械挖土方的体积应按槽底面积乘以挖土深度计算。槽底面积应以槽底的长乘以槽底的宽，槽底长和宽是指基础底宽外加工作面，当需要放坡时，应将放坡的土方量合并于总土方量中。 2 、开挖土方计算公式： (1) 、清单计算挖土方的体积：土方体积=挖土方的底面积X挖土深度。 (2) --------------------------------------------------------------------------------------------- 、定额规则：基槽开挖：V= (A+2C+X H) HXL。式中：V --------------------------------------------------------- 基槽土方量；A ----------- 槽底宽度；C———工作面宽度；H———基槽深度；L———基槽长度。. 其中外墙基槽长度以外墙中心线计算，内墙基槽长度以内墙净长计算，交接重合出不予 扣除。 基坑体积；A—基坑开挖：V=1/6H[A X B+a X b+(A+a) x(B+b)+a xb]。式中：V 基坑上口长度；B———基坑上口宽度；a———基坑底面长度；b———基坑底面宽度。
编订：__________________ 单位：__________________ 时间：__________________ 实验室安全标准操作规程 (正式) Standardize The Management Mechanism To Make The Personnel In The Organization Operate According To The Established Standards And Reach The Expected Level. Word格式 / 完整 / 可编辑
文件编号：KG-AO-5509-66 实验室安全标准操作规程(正式) 使用备注：本文档可用在日常工作场景，通过对管理机制、管理原则、管理方法以及管理机构进行设置固定的规范，从而使得组织内人员按照既定标准、规范的要求进行操作，使日常工作或活动达到预期的水平。下载后就可自由编辑。 1职责 1.1实验室主任对安全全面负责。经常进行安全督察，组织安全检查，负责处理安全事故。 1.2实验员负责水、电线路、消防器材的配置和设施安全检查。 1.3各科实验老师负责本科的化学药品、水电气、门窗的安全。 1.4实验员负责试剂、药品，特别是有毒有害，易燃、易爆物质的管理。 2. 工作程序 2.1 安全操作规范 2.1.1检测人员在工作中要严格按照操作规程，杜绝一切违章操作，发现异常情况立即停止工作，并及时登记报告。
2.1.2禁止用嘴、鼻直接接触试剂。使用易挥发、腐蚀性强、有毒物质必须带防护手套，并在通风橱内进行，中途不许离岗。 2.1.3在进行加热、加压、蒸馏等操作时，操作人员不得随意离开现场，若因故须暂时离开，必须委托他人照看或关闭电源。 2.1.4各种安全设施不许随意拆卸搬动、挪作他用，保证其完好及功能正常。 2.1.5操作人员要熟悉所使用的仪器设备性能和维护知识，熟悉水、电、燃气、气压钢瓶的使用常识及性能，遵守安全使用规则，精心操作。 2.2 有毒有害物质的管理 2.2.1化学试剂、药品中凡属易燃易爆，有毒(特别是剧毒物品)、易挥发产生有害气体的均应列为危险物品，严格分类，加强管理，专人负责。 2.2.2建立详细帐目，帐、物、卡相符，专人限量采购，入库检查。 2.2.3危险物品、易燃易爆物品单独存放，有毒
实验室安全操作规程 1、化验室安全操作规程 （1）实验前应做好准备，必须对所用药品与设备性能有充分的了解，熟悉每个具体操作中的安全注意事项。 （2）实验前必须熟悉实验室及其周围的环境和水龙头、电闸门的位置 （3）实验时应保持安静，思想要集中，遵守操作规程，切勿粗心大意，马马虎虎，更不准在实验室内开玩笑。 （4）严禁在实验室内饮食或煮食，或者把食具带劲实验室。 （5）每次实验完毕后应把手洗净，并检查水、电、气等安全措施完善后才能离开实验室（6）每个实验室都必须备有灭火器或砂土，并尽可能放在显眼的地方，能同事备有消防用的消防栓或水缸则更好 （7）实验室应保持空气流通，并设有专用的卫生箱，以供及时治疗的需要。常备药品有：红汞药水：供一般破伤使用 酒精：轻微的灼烧伤可用进过酒精的脱脂棉擦拭 5%硼酸氢钠溶液：受酸性物灼伤可用作冲洗 3%硼酸溶液：受碱性物灼伤可用作冲洗 还需要备有碘酒：紫药水及绷带和药棉 2、火和电的安全预防 （1）在使用中电气动力时，必须事先检查电开关，马达以及机械设备各部门是否安置妥善（2）开始工作时和停止工作时，必须将开关彻底扣严和拉下 （3）在更换保险丝时，要按负荷量，不得加大或以铜丝代替使用。 （4）严禁用湿手、湿布或铁柄毛刷等去清扫或擦拭电闸刀、点插销等，防止触电 （5）凡电气动力设备过热时，应立即停止运转 （6）定碳、定硫电炉或其他高温炉，其硅碳棒露出部分应设有安全罩，严禁将安置妥善的安全罩随意撤掉，以免发生触电事故。 （7）禁止洒水在电气设备和电线路上，以免漏电 （8）凡使用110伏以上电源装置，仪器的金属部分必须安装地线 （9）电热设备，例如马弗炉、烘箱、电炉和电热板等，所用电源的导线应经常注意检查其各接触处是否妥当，导线有无损坏和被腐蚀等 （10）马弗炉、烘箱等用电设备，使用时必须要有人负责照管，以防发生事故 （11）马弗炉需放在水泥等不燃物砌成的坚固台子上，不要靠近木板墙或木质门窗。（12）使用易燃物时，必须在距离火源较远的地方进行，绝不可靠近火源，尤其是乙醚着火的危险性极大，用时必须小心，用完后的剩余部分也应及时的存放到专门的安全地方。（13）绝不可以将氧气钢瓶存放在靠近电源的地方，并需防止强烈震动，气体出口活门处绝不可涂油和与有机物接触，以免发生爆炸的危险。 3、化学药品的安全预防 （1）距度星的药品，例如KCN、AS2O3等等，必须制定保管使用规则，并严格遵守，及时工作人员很少，也不可例外的有所忽视。这类药品不能与一般药品同样的存放和任意使用，即使用过后的余量已经很少也应及时送保管员及时查收，不应任意放在工作台上。 （2）内服有毒药品，如氰化物、铅化物、汞及汞化物、络酸盐、氧化砷钡盐等，应装在坚固的瓶中保管，禁止入口，与手接触用后要洗手。 （3）接触皮肤有毒的药品，例如氰化物、氟氢酸、溴水、过氯酸等，要装在严禁坚固的瓶中保管，使用时要特别小心，不得与皮肤接触。 （4）呼吸有毒药品（及有毒气体和蒸气）如氰化氢、氮的氧化物、氯化氢、硫化氢、溴、
灯具生产制造相关的安规认证知识 灯具：凡是能分配，透出或转变一个或多个光源发出的光线的一种器具，并包括支撑、固定和保护光源必需的部件（但不包括光源本身），以及必需的电路辅助装置和将它们与电源连接的设施 一．相关定义 1．灯具：凡是能分配，透出或转变一个或多个光源发出的光线的一种器具，并包括支撑、固定和保护光源必需的部件（但不包括光源本身），以及必需的电路辅助装置和将它们与电源连接的设施。 2．普通灯具：提供防止与带电部件意外接触的保护，但没有特殊的防尘、防固体异物和防水等级的灯具。 3．可移动式灯具：正常使用时，灯具连接到电源后能从一处移动到另一处的灯具。 4．固定式灯具：不能轻易的从一处移动到另一处的灯具，因为固定以致于这种灯具只能借助于工具才能拆卸。 5．嵌入式灯具：制造商指定完全或部分嵌入安装表面的灯具。 6．带电部件：在正常使用过程中，可能引起触电的导电部件。中心导体应当看作是带电部件。 7．EN安全特低电压（SELV－safety extra-low voltage）：在通过诸如安全隔离变压器或转换器与供电电源隔离开来的电路中，在导体之间或在任何导体与接地之间，其交流电压有效值不超过50V。 8．UL低压线路：开路电压不超过交流电压有效值30V的线路。 9．基本绝缘（EN）：加在带电部件上提供基本的防触电保护的绝缘。耐压应在2U+1000V 以上（U：当地的电网电压）。 10．补充绝缘（EN）：附加在基本绝缘基础上的独立的绝缘，用于基本绝缘失效时提供防触电保护。耐压值应在2U+1750V以上（单层）。 11．双层绝缘（EN）：基本绝缘与补充绝缘组成的绝缘，耐压值应在4U+2750V以上（即基本绝缘与补充绝缘耐压之和）。 12．增强绝缘（EN）：绝缘效果与双层绝缘相当的一种加强性绝缘。从总体上看，一般只为一层，但也可由多层组成，且各层不可明确进行分割并单独测量。耐压值应在4U+2750V 以上。 13．CLASS O级灯（EN）：仅以基本绝缘为电击保护措施的灯具，无接地等保护措施。14．CLASS I级灯（EN）：除了基本绝缘为电击保护措施外，还采用了其它如接地等保护性措施的灯具。 15．CLASS II级灯具（EN）：采取双重绝缘或增加绝缘为电击保护措施的灯具。其绝缘效果不依赖于接地或安装条件。 16．CLASS III级灯（EN）：使用特低安全电压（SELV）为防电击保护方式的灯具。17．普通可燃材料（normally flammable material）：材料的引燃温度至少为200℃，并且在此温度时该材料不至于变形或强度降低。例如木材及厚度大于2mm的以木材为基质的材料。 18．易燃材料（readily flammable material）：普通可燃材料和非可燃材料以外的一种材料。 例如木纤维和厚度小于2的以木材为基质的材料。 19．非可燃材料（non-combustible material）：不能助燃的材料。例如金属、水泥等。 20：定型试验（type test）：对定型试验样品进行测试，其目的是检验某一给定产品的设计是
.. 一级建造师《建设工程经济》计算公式汇总 1、等额支付系列的终值、现值、资金回收和偿债基金计算 等额支付系列现金流量序列是连续的，且数额相等，即： ） ，，，，常数（n t A A t 321①终值计算（即已知 A 求F ） i i A F n 1 1 ）（②现值计算（即已知 A 求P ） n n n i i i A i F P ） （）（） （1111 ③资金回收计算（已知 P 求A ） 1 1 1 n n i i i P A ）（）（④偿债基金计算（已知 F 求A ） 1 1 n i i F A ） （2、有效利率的计算 包括计息周期有效利率和年有效利率两种情况。（2）年有效利率，即年实际利率。年初资金P ，名义利率为r ，一年内计息m 次，则计息周期利率为 m r i 。根据一次支付终值公式可得该年的 本利和F ，即： m m r P F 1 根据利息的定义可得该年的利息I 为： 1 1 1 m m m r P P m r P I 再根据利率的定义可得该年的实际利率，即有效利率 i eFF 为： 1 1 i eff m m r P I 3、财务净现值 t c t n t i CO CI FNPV 1 式中 FNPV ——财务净现值； （CI-CO ）t ——第t 年的净现金流量（应注意“＋” 、“-”号）； i c ——基准收益率；n ——方案计算期。
.. 4、财务内部收益率（FIRR ——Financial lnternaI Rate oF Return ） 其实质就是使投资方案在计算期内各年净现金流量的现值累计等于零时的折现率 。其数学表达式为： t t n t FIRR CO CI FIRR FNPV 10 式中 FIRR ——财务内部收益率。 5、投资收益率指标的计算 是投资方案达到设计生产能力后一个正常生产年份的年净收益总额（ 不是年销售收入）与方案投资总额（包括 建设投资、建设期贷款利息、流动资金等） 的比率： % 100I A R 式中 R ——投资收益率； A ——年净收益额或年平均净收益额；I ——总投资 6、总投资收益率 总投资收益率（ROI ）表示总投资的盈利水平 % 100TI EBIT ROI 式中 EBIT-----技术方案正常年份的年息税前利润或运营期内平均息税前利润； TI------技术方案总投资包括建设投资、建设期利息和全部流动资金。7、资本金净利润率（ ROE ） 技术方案资本金净利润率（ ROE ）表示技术方案盈利水平 % 100EC NP ROE 式中 NP----技术方案正常年份的年净利润或运营期内年平均净利润，净利润＝利润总额-所得税 EC----技术方案资本金 8、静态投资回收期 ·当项目建成投产后各年的净收益（即净现金流量）均相同时，静态投资回收期计算： A I P t 式中 I ——总投资；A ——每年的净收益。 ·当项目建成投产后各年的净收益不相同时，静态投资回收期计算： 流量 出现正值年份的净现金 的绝对值 上一年累计净现金流量 现正值的年份数 累计净现金流量开始出 1 －t P 9、借款偿还期 余额 盈余当年可用于还款的 盈余当年应偿还借款额的年份数 借款偿还开始出现盈余 1 －d P 10、利息备付率 利息备付率＝息税前利润 /计入总成本费用的应付利息。 式中：息税前利润——即利润总额与计入总成本费用的利息费用之和（不含折旧、摊销费 11、偿债备付率 偿债备付率＝（息税前利润加折旧和摊销-企业所得税）/应还本付息的金额 式中：应还本付息的资金——包括当期还贷款本金额及计入总成本费用的全部利息； 息税前利润加折旧和摊销 -企业所得税＝净利润 +折旧+摊销+利息
实验室安全操作规程 Document number：WTWYT-WYWY-BTGTT-YTTYU-2018GT
实验室安全操作规程 1目的 规范化验室的管理，确保实验条件符合实验要求，保障实验人员在实验过程中的安全和健康。 2适用范围 本文件适用于实验室内安全操作工作。 3职责 化验人员必须严格按照实验室安全操作，对任何实验室内任何安全违章行为隐患予以指出和纠正并及时向主管人员汇报。实验室负责人须负责安全操作规程的指令执行与检查。 4管理要求 4.1电气设备安全规则 4.1.1使用电气设备时，须事先检查开关、电机、以及机械设备，确认各部分是否安置妥当。并对相关设施和状态标志进行严格检查，确认安全（完好）后再进行操作，严禁或在眼睛旁视时开关电闸和电器开关。 4.1.2在使用电炉时、马弗炉、烘箱等高温器具时，与其它物品一定要保持安全距离并定期巡视。 4.1.3严禁用导电器具和湿布擦洗电器；严禁用湿手分、合开关或接触电气设备；更换保险丝时应由电工按负荷选用保险丝，不得随意加大或以铜丝代替使用。 4.2化学试剂规则 4.2.1操作硝酸、浓硫酸、氢氟酸、浓碱、酚等强腐蚀试剂时必须戴上橡皮手套，配带防护眼镜等谨慎操作，防止喷溅；在开启乙醚、氨水等刺激性强，极易挥发的试剂瓶时，瓶口不得对准自己和他人；一切发生有毒有害的操作须在通风橱内进行。 4.2.2在进行可燃料物品（如汽油、酒精、乙醚等有机溶剂）有关的一切操作时，周围环境温度不宜太高，另外远离明火（火源）。蒸馏易挥发和易燃液体
的器皿须完整无缺，禁止明火直接加热。 4.2.3严禁食具和器具混在一起或互相挪用；严禁试剂入口，如以鼻鉴别时用手轻轻扇动稍闻其气味；配制溶液有发热现象产生的操作时，必须置于耐热容器中进行。配制酸溶液须缓缓将浓酸加入水中，同时用玻璃棒随时搅拌。 4.2.4一切固体不溶物、浓酸及有毒害液体严禁倒入水槽。所有装有药品的瓶子均应贴有明显的标签，并分类、分层、分室存放。禁止使用没有标签的药品。 4.2.5腐蚀性强烈的物质有： 溴及溴水、硝酸、硫酸、王水、氢氟酸、铬酸溶液、氢氰酸、五氧化二磷、磷酸、氢氧化钾、氢氧化钠、氢氧化铵、冰醋酸、磷、硝酸银、盐酸等。 4.2.6易燃物质有： 醇类、醚类、丙酮、苯、甲苯、酚、汽油、二硫化碳、磷、过氧化钠、、碳化钙、金属钾、钠、镁等。 4.2.7有毒害气体有：一氧化碳、硫化氢、氟化氢、二硫化碳、氯化氢、氯、碘、二氧化硫、二氧化氮等 4.3易爆品安全规则 4.3.1仔细检查供真空操作的全部仪器有无裂缝；使用前检查容器真空度是否 合格。 4.3.2使用气瓶时，需固定好且不可超定检周期使用；不得碰撞或冲击气瓶；须有减压阀且开气时气嘴不可对人；气瓶不可放在电炉、暖气附近，不能放在日光照射的地方；氧气瓶禁止与油类物质接触。 4.3.3有爆炸危险性的药品（如过氧化钠、过氧化氢、浓高氯酸等）在实验室只可放一小部分，并存放在干燥阴凉处。 4.3.4禁止将性质相抵触的能引起燃烧爆炸的物品贮存在一块，使用时应保存足够的安全距离。如：禁止浓硫酸和结晶状高锰酸钾接触；禁止有机物和浓硝酸一起混合及加热。 4.3.5一旦发生失火事故，首先撤除一切热源，关闭电闸，然后用砂子或石棉布盖住失火地点或用四氯化碳等灭火器等灭火。 4.4使用毒害品安全规则
操作规程编号：YTO-FS-PD576 挖土工程安全操作规程通用版 In Order T o Standardize The Management Of Daily Behavior, The Activities And T asks Are Controlled By The Determined Terms, So As T o Achieve The Effect Of Safe Production And Reduce Hidden Dangers. 标准/ 权威/ 规范/ 实用 Authoritative And Practical Standards
挖土工程安全操作规程通用版 使用提示：本操作规程文件可用于工作中为规范日常行为与作业运行过程的管理，通过对确定的条款对活动和任务实施控制,使活动和任务在受控状态，从而达到安全生产和减少隐患的效果。文件下载后可定制修改，请根据实际需要进行调整和使用。 一、进入现场必须遵守安全生产六大纪律。 二、挖土中发现管道、电缆及其他埋设应及时报告，不得擅自处理。 三、挖土时要注意土臂的稳定性，发现有裂缝及倾坍可能时，人员应立即离开并及时处理。 四、人工挖土，前后操作人员间距不应小于2～3m，堆土要在1m以外，并且高度不得超过1.5m。 五、每日或雨后必须检查土臂及支撑稳定情况，在确保安全的情况下继续工作，并且不得将土和其他物件堆在支撑上，不得在支撑下行走或站立。 六、机械挖土，启动前应检查离合器、钢丝绳等，经空车试运转正常后再开始作业。 七、机械操作中进铲不应过深，提升不应过猛。 八、机械不得在输电线路下工作，应在输电线路一侧工作，不论在任何情况下，机械的任何部位与架空输电线路的最近距离应符合安全操作规程要求。 九、机械应停在坚实的地基上，如基础过差，应采取
一、生物安全实验室操作规程 实验室生物安全管理程序 1.目的，有效地针对科室进行全面的生物安全管理，确保工作人员的安全。 2. 适用范围：适用于科室各专业实验室。 3、职责 、科主任负责任命生物安全小组，指导，规范其工作。 、生物安全小组组长负责安全小组日常工作的安排。 、生物安全小组负责科室安全的具体工作。 4、工作程序 、生物安全小组组成 、科主任指定安全小组组长 、经年度考核，从科室成员中选拨具有高度责任心和实验室知识的技术骨干，由科主任命为生物安全小组安全成员。由3人组成。安全小组成员任期一年，任期中出现特殊情况科主任可对之罢免。 、实验室生物安全的维护和检查 、生物安全小组指定针对安全操作和安全装备的检查方案，至少每年检查一次。 、生物安全小组建立安全清单，为回顾性检查提供资料并进行记录，形成《安全记录》。 、对危险品、危险区进行鉴定并加以标志。 、实验室应按规定及时报告所有的事件和潜在的危险因素。 、安全小组应定期对工作人员进行安全培训教育，并对各种紧急情况下应急措施进行培训。
、若发生职业暴露应及时报告科主任和生物安全小组人员。 、警告标记和标签的建立。 、对不因危险程度的实验工作区进行标志。 、对高度危险性区域要张贴危险公告。 、装存危险物质的容器必须贴上标签，其内容应详细。 5、安全操作规程 、临检、生化、免疫、血库等实验室生物安全防护 、在实验室工作区禁止吸烟 、禁止在实验室放置食物、饮料及类似的存在有潜在的从手 到口的接触途径的其他物质。禁止用实验室的冰箱（柜）储存食物。 、处理腐蚀性或毒性物质时必须做好防护工作。应使用安全镜、面罩或其他的眼睛和面部防护用品。 、在实验室工作区，病区应穿白大衣或隔离衣，服装应符合实验室设备的要求。 、应穿着舒适，防滑并能保护整个脚面的鞋子。 、在实验工作区头发不可下垂，避免与污染物质接触或影响实验操作，有此类危险的饰物应避免带入工作区。不可留长胡须。 、由实验工作区进入非污染区要洗手，接触污染物后要立即洗手。 、实验室禁止堆积过多的垃圾，至少应每日清理一次。 、禁止在实验工作区存放个人物品。 、在实验室指定清洁区和非清洁区，非本室工作人员禁止进入工作区。 、从移液器吸取液体、禁止口吸。