CN107256336B - Helicobacter pylori Antibiotic Sensitivity and the quantizating index of drug resistance determine method - Google Patents
Helicobacter pylori Antibiotic Sensitivity and the quantizating index of drug resistance determine method Download PDFInfo
- Publication number
- CN107256336B CN107256336B CN201710418099.0A CN201710418099A CN107256336B CN 107256336 B CN107256336 B CN 107256336B CN 201710418099 A CN201710418099 A CN 201710418099A CN 107256336 B CN107256336 B CN 107256336B
- Authority
- CN
- China
- Prior art keywords
- helicobacter pylori
- antibiotic
- curve
- fractional order
- equivalent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16C—COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE
- G16C20/00—Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
- G16C20/50—Molecular design, e.g. of drugs
Landscapes
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Computational Biology (AREA)
- Computing Systems (AREA)
- Theoretical Computer Science (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention discloses the quantizating index of a kind of helicobacter pylori Antibiotic Sensitivity and drug resistance to determine method, this method establishes the fractional order equivalent-circuit model that helicobacter pylori reacts with antibiotic to growth/killing curve of antibiotic using helicobacter pylori, and being associated with for sensibility and Resistance Mechanism inside model parameter and bacterium is established, to quantitatively portray the mechanism of helicobacter pylori Antibiotic Sensitivity and drug resistance and provide quantization New Set for clinical examination.
Description
Technical field
The invention belongs to quantizating index calculating field more particularly to a kind of helicobacter pylori Antibiotic Sensitivity and drug resistances
The quantizating index of property determines method.
Background technique
1994 the World Health Organization/international cancer research institution (WHO/IARC) that helicobacter pylori is set to I class is carcinogenic
It is former.Epidemiological study shows that helicobacter pylori Natural infection rate is more than 50% in world wide, in the world almost without one kind
Pathogenic microorganism is infected global half crowd.China is the district occurred frequently of gastric cancer, the high infection rate of this and helicobacter pylori
Closely related (70%), therefore the key for controlling incidence gastric cancer rate is the treatment of helicobacter pylori.
There is its limitation for the gastric cancer primary prevention for removing helicobacter pylori at present, it will cause abuse of antibiotics, epidemic disease
The effect of seedling has to be evaluated.The classical way of the classic treatment helicobacter pylorus infection of world health organisation recommendations is " triple therapy "
(proton pump inhibitor add metronidazole, two kinds in Amoxicillin and three kinds of antibiotic of clarithromycin), however in recent years " three
The cure rate of therapy " declines year by year, and main cause is that the resistant rate of helicobacter pylori rises year by year, and the generation source of resistant rate is
The unreasonable use of antibiotic, cannot be enough or be excessively used antibiotic and can result in drug-fast bacteria generation, and bacterium
Aging also influences its drug resistance, so the clinical antibiotics common dose (a certain certain concentration) estimated can not remove institute completely
There is bacterium, therefore, accurate calculating is a problem for the antibiotic usage dosage of specific patient.
Due to patient individual difference and infect helicobacter pylori thallus difference cause the dosage of antibiotic with
The course for the treatment of cannot be unalterable, this just needs to provide an optimal control therapeutic scheme, makes patient under the guidance of this scheme
Hp Drug Resistance rate can have not only been reduced with antibiotic but also cure rate can be improved, and the two is made to reach " harmony " index.
Helicobacter pylori gene expression profile under prioritization scheme is monitored simultaneously screens antibiotics target spot.Meanwhile the generation of bacterial drug resistance
Modern medicine achievement is placed in desperate situation, the treatment of effective antibiotics and does not prevent to infect, organ transplant, cancer chemotherapy and
The success rate of the treatments such as major surgery also has no way of ensureing.Therefore sensibility of bacteria on antibiotic and drug resistance Journal of Sex Research are global concerns
The problem of, also it is important clinical and basic problem in science.
Summary of the invention
In order to solve the deficiencies in the prior art, the present invention provides a kind of helicobacter pylori Antibiotic Sensitivity and drug resistances
The quantizating index of property determines method, has got through the association of external characteristics in helicobacter pylori Antibiotic Sensitivity and drug resistance,
Its fractional order quantization New Set is extracted, the discovery for clinical examination treatment and novel targets provides completely new thinking.
A kind of helicobacter pylori Antibiotic Sensitivity of the invention and the quantizating index of drug resistance determine method, comprising:
Step 1: the fractional order equivalent-circuit model that building helicobacter pylori reacts with antibiotic, wherein helicobacter pylori
The input of the fractional order equivalent-circuit model reacted with antibiotic is the concentration of antibiotic, and output is killing curve；According to equivalent
Circuit model lists growth curve/killing curve time-domain expression；
Step 2: the growth of H. pylori curve data that experiment is measured substitutes into growth curve/killing curve time domain table
Up to formula, the range of the capacitor fractional order order α of the time-domain expression and the value of other relevant parameters are picked out；
Step 3: repeating step 2, killing curve experimental data of the several groups under different antibiotic concentrations is substituted into growth
Curve/killing curve time-domain expression, and carry out curve fitting；
Step 4: the case where judging whether there is over-fitting, the fractional order for determining that helicobacter pylori reacts with antibiotic are equivalent
The final structure and growth curve/killing curve time-domain expression of circuit model；
Step 5: according to the range of α in step 2, traversing the value of fractional order order α, the corresponding one group of fitting ginseng of each α value
Several values compares the fitting result of each group of parameter and former experimental result curve, corresponding one when taking error minimum
Group parameter is optimized parameter.
Further, this method further includes the fractional order equivalent-circuit model verifying helicobacter pylori and reacting with antibiotic
Accuracy, detailed process are as follows:
Introduce two nonlinear functions N1 and N2 according to current all trust datas, and determine nonlinear function N1 and N2 with
The serial relation of antibiotic concentration, and its irrelevance with α is separately verified, and then verify the standard of fractional order equivalent circuit mould
True property.
Wherein, this group of nonlinear function of nonlinear function N1 and N2 is that experiment is mutual to clarithromycin with helicobacter pylori
Specific function when effect, it is insensitive to the variation of other parameters, and face when sample size is sufficiently large for direct parameter guidance
Bed can directly quantify the inside recombination mechanism for reflecting helicobacter pylori and antibiotic interaction.When sample is less than Shi Kezuo
Single situation is analyzed for indirect parameter.
Further, in the step 2, pick out capacitor fractional order order α's using non-linear least square method
The value of range and other relevant parameters.
Further, it in the step 3, is carried out curve fitting using nonlinear least square method.
Further, in the step 4, the estimated value and AIC criterion of application time constant judged whether there is quasi-
The case where conjunction.
According to AIC criterion, the form of low single order should be used in the case where high-order model fractional order order is almost the same, it is no
The case where then occurring as soon as over-fitting, so by the knot of model in this test acted on for helicobacter pylori and clarithromycin
Structure is set to the equivalent circuit containing only a RC link.
Further, in the fractional order equivalent-circuit model that helicobacter pylori reacts with antibiotic, helicobacter pylori is
The voltage source that one voltage slowly rises.
Further, in the fractional order equivalent-circuit model that helicobacter pylori reacts with antibiotic, killing curve is corresponding
The load of equivalent circuit.
It further, also include an electricity in the fractional order equivalent-circuit model that helicobacter pylori reacts with antibiotic
Several RC links of resistance and series connection with it.
Further, the capacitor in all RC links is fractional order capacitor.
In equivalent circuit of the invention, because occurring heavy-tailed phenomenon in killing curve, in all RC links
Capacitor is fractional order capacitor.
Further, in the step 5, after determining parameter, it counter can solve helicobacter pylori and be reacted with antibiotic
Fractional order equivalent-circuit model in resistance and resistance and capacitance in each RC link.
Wherein, helicobacter pylori should have relatively-stationary structure to the mechanism model of antibiotic.
Compared with prior art, the beneficial effects of the present invention are:
This method of the invention extracts key parameter by growth curve/killing curve, and has got through helicobacter pylori
The association of external characteristics in Antibiotic Sensitivity and drug resistance has extracted its fractional order quantization New Set, has controlled for clinical examination
It treats and the discovery of novel targets provides completely new thinking.
Detailed description of the invention
The accompanying drawings constituting a part of this application is used to provide further understanding of the present application, and the application's shows
Meaning property embodiment and its explanation are not constituted an undue limitation on the present application for explaining the application.
Fig. 1 is the equivalent circuit universal model of helicobacter pylori Yu the antibiotic mechanism of action；
Fig. 2 is single order RC (optimal) equivalent-circuit model of helicobacter pylori Yu the clarithromycin mechanism of action；；
Fig. 3 is fitting result and former experimental result comparison diagram；
Fig. 4 is two nonlinear characteristic functions of helicobacter pylori and clarithromycin interaction and its low spirit to parameter
Sensitivity verifying.
Specific embodiment
It is noted that following detailed description is all illustrative, it is intended to provide further instruction to the application.Unless another
It indicates, all technical and scientific terms used herein has usual with the application person of an ordinary skill in the technical field
The identical meanings of understanding.
It should be noted that term used herein above is merely to describe specific embodiment, and be not intended to restricted root
According to the illustrative embodiments of the application.As used herein, unless the context clearly indicates otherwise, otherwise singular
Also it is intended to include plural form, additionally, it should be understood that, when in the present specification using term "comprising" and/or " packet
Include " when, indicate existing characteristics, step, operation, device, component and/or their combination.
By taking helicobacter pylori and clarithromycin as an example, builds equivalent-circuit model and refer to that applied mathematics theory is as detailed as possible
The kinetics relation of external characteristics and internal mechanism when helicobacter pylori reacts with clarithromycin is described to the greatest extent.Wherein, external characteristics refers to
Be the killing curve generated with various concentration clarithromycin and when helicobacter pylori activity, internal mechanism refers to helicobacter pylori
The influence of sensibility and drug resistance to sterilization process to clarithromycin.In equivalent-circuit model, it is deep and remote for loading corresponding
Helicobacter pylorus is indicated inside the box of the external behavior that Helicobacter pylori is reacted with clarithromycin, i.e. killing curve, Fig. 1 and Fig. 2
Internal mechanism part of the bacterium to clarithromycin.
A kind of helicobacter pylori Antibiotic Sensitivity of the invention and the quantizating index of drug resistance determine method, comprising:
Step 1: the fractional order equivalent-circuit model that building helicobacter pylori reacts with antibiotic, wherein helicobacter pylori
The input of the fractional order equivalent-circuit model reacted with antibiotic is the concentration of antibiotic, and output is killing curve；According to equivalent
Circuit model lists growth curve/killing curve time-domain expression.
1) foundation of equivalent-circuit model
Helicobacter pylori is assumed with the fractional order equivalent-circuit model of clarithromycin as shown in Figure 1, its corresponding fractional order
Transmission function form are as follows:
(1) is obtained as inverse Laplace transform
Wherein constant M is antibiotic concentration/MIC.
(2) formula is converted to
Later, target is converted to α, a0,a1,a2,a3,a4... the estimation of several parameters.
Wherein, helicobacter pylori is the special voltage source (natural propagation of bacterium) that a voltage slowly rises, and sterilization is bent
Line corresponds to the load (MIC multiple) of equivalent circuit.
It is also several comprising a resistance and series connection with it in the equivalent circuit that the present invention is applicable in addition, according to AIC criterion
A RC link.
In equivalent circuit of the invention, because occurring heavy-tailed phenomenon in killing curve, in all RC links
Capacitor is fractional order capacitor.
Step 2: the growth of H. pylori curve data that experiment is measured substitutes into growth curve/killing curve time domain table
Up to formula, the range of the capacitor fractional order order α of the time-domain expression and the value of other relevant parameters are picked out.
In the step 2, using non-linear least square method pick out capacitor fractional order order α range and other
The value of relevant parameter.
Step 3: repeating step 2, killing curve experimental data of the several groups under different antibiotic concentrations is substituted into growth
Curve/killing curve time-domain expression, and carry out curve fitting.
In the step 3, carried out curve fitting using nonlinear least square method.
Step 4: the case where judging whether there is over-fitting, the fractional order for determining that helicobacter pylori reacts with antibiotic are equivalent
The final structure and growth curve/killing curve time-domain expression of circuit model.
In the step 4, the case where estimated value and AIC criterion of application time constant judge whether there is over-fitting.
According to AIC criterion, the form of low single order should be used in the case where high-order model fractional order order is almost the same, it is no
The case where then occurring as soon as over-fitting, so by the knot of model in this test acted on for helicobacter pylori and clarithromycin
Structure is set to the equivalent circuit containing only a RC link.
2) parameter and model structure are estimated
After above-mentioned equivalent-circuit model is tentatively established, the problem of Model Parameter recognizes is defined as: adopted in given experiment
The inputoutput data ((u (1) collected, y (1)), (u (2), y (2)) ... (u (N), y (N)), searching makes fractional order equivalent circuit
The fractional order and relevant parameter of model make the curve error of matched curve and experimental data minimum.It will be collected in original experiment
Each group of data is updated in (3) formula respectively and is fitted with nonlinear least square method, finds parameter a1,a3It is almost the same, according to
AIC criterion should use the form of low single order in the case where high-order model fractional order order is almost the same, otherwise occur as soon as quasi-
The case where conjunction, so the structure of model is set to containing only one in this test of helicobacter pylori and clarithromycin effect
The equivalent circuit of a RC link.
Step 5: according to the range of α in step 2, traversing the value of fractional order order α, the corresponding one group of fitting ginseng of each α value
Several values compares the fitting result of each group of parameter and former experimental result curve, corresponding one when taking error minimum
Group parameter is optimized parameter.
In the step 5, after determining parameter, the fractional order etc. that helicobacter pylori reacts with antibiotic counter can be solved
Imitate the resistance in circuit model and resistance and capacitance in each RC link.
Wherein, helicobacter pylori should have relatively-stationary structure to the mechanism model of antibiotic.
3) experimental verification
This method further includes verifying the accuracy for the fractional order equivalent-circuit model that helicobacter pylori reacts with antibiotic,
Detailed process are as follows:
Introduce two nonlinear functions N1 and N2 according to current all trust datas, and determine nonlinear function N1 and N2 with
The serial relation of antibiotic concentration, and its irrelevance with α is separately verified, and then verify the standard of fractional order equivalent circuit mould
True property.
Wherein, this group of nonlinear function of nonlinear function N1 and N2 is that experiment is mutual to clarithromycin with helicobacter pylori
Specific function when effect, it is insensitive to the variation of other parameters, and face when sample size is sufficiently large for direct parameter guidance
Bed can directly quantify the inside recombination mechanism for reflecting helicobacter pylori and antibiotic interaction.When sample is less than Shi Kezuo
Single situation is analyzed for indirect parameter.
According to new model structure, again repeatedly 2), collected data are updated in (3) formula.In view of the present invention
The practical significance of middle parameter, all parameters must all be greater than 0, and fractional order order is between 0 to 1.For dividing
Number rank order α uses Interval partition method, and other parameters is cooperated to estimate jointly.For the nonlinear characteristic for embodying model, N is introduced1
(M) and N2(M) two nonlinear functions, thus finally obtained model are as follows:
WhereinIt is all non-sensitive parameter a respectively0, a1, a2Expectation, N1(M) withProduct be equal to not
With a under concentration0, N2(M) effect having the same, to go to indicate helicobacter pylorus under several groups various concentration with a model
The response situation of bacterium and clarithromycin.This group of nonlinear function is tested with helicobacter pylori to clarithromycin interaction when institute
Distinctive function, it is insensitive to the variation of other parameters.
Parameter is substituted into the matched curve such as Fig. 3 obtained after the corresponding equation (3) of equivalent-circuit model in the present invention
It is shown.N1(M) and N2(M) function curve is as shown in Figure 4.Instead solving through parameter can get R0, R1And C1WithWithRatio
Example relationship.Above-mentioned all quantizating index α, R0, R1And C1, and test with helicobacter pylori to clarithromycin unintentional nonlinearity
Function N1(M) and N2(M) there is distinct practical significance (as shown in table 1), can be clinical inspection by a certain number of measured datas
It tests treatment and the discovery of novel targets provides important references.
Table 1
| Parameter | Related internal characteristic |
| α | The rate that antibiotic is spread inside bacterium |
| R1=Vec(0)/M | Drug resistance (negative correlation) |
| C1 | The genetic mechanism of bacterium |
| R1 | Drug resistance (positive correlation) |
| N1And N2 | The intrinsic property of bacterial antibiotic |
Above-mentioned, although the foregoing specific embodiments of the present invention is described with reference to the accompanying drawings, not protects model to the present invention
The limitation enclosed, those skilled in the art should understand that, based on the technical solutions of the present invention, those skilled in the art are not
Need to make the creative labor can make various modifications or changes (as with time constant invariance various bacterium with
Antibiotic and combinations thereof) still within protection scope of the present invention.
Claims (10)
1. a kind of helicobacter pylori Antibiotic Sensitivity and the quantizating index of drug resistance determine method characterized by comprising
Step 1: the fractional order equivalent-circuit model that react with antibiotic of building helicobacter pylori, wherein helicobacter pylori with resist
The input of the fractional order equivalent-circuit model of raw element reaction is the concentration of antibiotic, and output is killing curve；According to equivalent circuit
Model lists the time-domain expression of growth curve and killing curve；
Step 2: the growth of H. pylori curve data that experiment measures is substituted into the time domain of growth curve and killing curve respectively
Expression formula picks out capacitor and electricity in the range and equivalent-circuit model of the capacitor fractional order order α of the time-domain expression
The value of resistance；
Step 3: repeating step 2, killing curve experimental data of the several groups under different antibiotic concentrations is substituted into growth respectively
The time-domain expression of curve and killing curve, and carry out curve fitting；
Step 4: the case where judging whether there is over-fitting determines the fractional order equivalent circuit that helicobacter pylori reacts with antibiotic
The final structure and growth curve of model and the time-domain expression of killing curve；
Step 5: according to the range of α in step 2, the value of fractional order order α is traversed, the corresponding one group of fitting parameter of each α value
Value compares the fitting result of each group of parameter and original experimental result curve, one group of corresponding ginseng when taking error minimum
Number is optimized parameter.
2. a kind of quantizating index determination side of helicobacter pylori Antibiotic Sensitivity and drug resistance as described in claim 1
Method, which is characterized in that this method further includes verifying the standard for the fractional order equivalent-circuit model that helicobacter pylori reacts with antibiotic
True property, detailed process are as follows:
Two nonlinear functions N1 and N2 are introduced according to current all trust datas, and determine nonlinear function N1 and N2 and antibiosis
The serial relation of plain concentration, and its irrelevance with α is separately verified, verify the accuracy of fractional order equivalent circuit mould.
3. a kind of quantizating index determination side of helicobacter pylori Antibiotic Sensitivity and drug resistance as described in claim 1
Method, which is characterized in that in the step 2, the range of capacitor fractional order order α is picked out using non-linear least square method
With the value of capacitor and resistance in equivalent-circuit model.
4. a kind of quantizating index determination side of helicobacter pylori Antibiotic Sensitivity and drug resistance as described in claim 1
Method, which is characterized in that in the step 3, carried out curve fitting using nonlinear least square method.
5. a kind of quantizating index determination side of helicobacter pylori Antibiotic Sensitivity and drug resistance as described in claim 1
Method, which is characterized in that in the step 4, the case where judging whether there is over-fitting using AIC criterion.
6. a kind of quantizating index determination side of helicobacter pylori Antibiotic Sensitivity and drug resistance as described in claim 1
Method, which is characterized in that in the fractional order equivalent-circuit model that helicobacter pylori reacts with antibiotic, helicobacter pylori is one
The voltage source that voltage slowly rises.
7. a kind of quantizating index determination side of helicobacter pylori Antibiotic Sensitivity and drug resistance as described in claim 1
Method, which is characterized in that in the fractional order equivalent-circuit model that helicobacter pylori reacts with antibiotic, killing curve corresponds to equivalent
The load of circuit.
8. a kind of quantizating index determination side of helicobacter pylori Antibiotic Sensitivity and drug resistance as described in claim 1
Method, which is characterized in that in the fractional order equivalent-circuit model that helicobacter pylori reacts with antibiotic, also comprising resistance and
Several RC links of series connection with it.
9. a kind of quantizating index determination side of helicobacter pylori Antibiotic Sensitivity and drug resistance as claimed in claim 8
Method, which is characterized in that the capacitor in all RC links is fractional order capacitor.
10. a kind of quantizating index determination side of helicobacter pylori Antibiotic Sensitivity and drug resistance as described in claim 1
Method, which is characterized in that in the step 5, after determining parameter, counter can solve point that helicobacter pylori reacts with antibiotic
Resistance in number rank equivalent-circuit model and resistance and capacitance in each RC link.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710418099.0A CN107256336B (en) | 2017-06-06 | 2017-06-06 | Helicobacter pylori Antibiotic Sensitivity and the quantizating index of drug resistance determine method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710418099.0A CN107256336B (en) | 2017-06-06 | 2017-06-06 | Helicobacter pylori Antibiotic Sensitivity and the quantizating index of drug resistance determine method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107256336A CN107256336A (en) | 2017-10-17 |
| CN107256336B true CN107256336B (en) | 2019-10-29 |
Family
ID=60023934
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710418099.0A Active CN107256336B (en) | 2017-06-06 | 2017-06-06 | Helicobacter pylori Antibiotic Sensitivity and the quantizating index of drug resistance determine method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107256336B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020258515A1 (en) * | 2019-06-28 | 2020-12-30 | 浙江大学 | Method for realizing multi-column continuous flow chromatography design and analysis |
| CN116313149B (en) * | 2023-03-09 | 2024-04-02 | 深圳市检验检疫科学研究院 | Method and system for detecting bacterial drug resistance |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102621388A (en) * | 2012-04-13 | 2012-08-01 | 山东电力集团公司潍坊供电公司 | Electric transmission line lumped parameter on-line determination method based on synchronous time domain signals |
| US9267997B2 (en) * | 2012-10-25 | 2016-02-23 | Bayerische Motoren Werke Aktiengesellschaft | Systems and methods to determine the condition of a battery |
| CN103093081B (en) * | 2012-12-15 | 2016-08-17 | 西南科技大学 | A kind of analogy method of induced with laser biological tissue photo-thermal effect |
| CN103678907B (en) * | 2013-12-04 | 2016-10-05 | 哈尔滨工业大学 | The fractional differentiation recognizer of steel and concrete structure Corrosion Electrochemical Characteristics |
| CN106354962A (en) * | 2016-08-02 | 2017-01-25 | 电子科技大学 | Lithium-iron-phosphate-battery fractional-order equivalent circuit model establishing method based on frequency demultiplication representation |
-
2017
- 2017-06-06 CN CN201710418099.0A patent/CN107256336B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN107256336A (en) | 2017-10-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Moran et al. | Meta-analysis of controlled trials of ventilator therapy in acute lung injury and acute respiratory distress syndrome: an alternative perspective | |
| Samia et al. | Extraction site location and incisional hernias after laparoscopic colorectal surgery: should we be avoiding the midline? | |
| Fraser et al. | A complete course of intravenous antibiotics vs a combination of intravenous and oral antibiotics for perforated appendicitis in children: a prospective, randomized trial | |
| Horrace et al. | Multiple comparisons with the best, with economic applications | |
| Havelaar et al. | Disease burden in The Netherlands due to infections with Shiga toxin-producing Escherichia coli O157 | |
| CN107256336B (en) | Helicobacter pylori Antibiotic Sensitivity and the quantizating index of drug resistance determine method | |
| Su et al. | Random forests of interaction trees for estimating individualized treatment effects in randomized trials | |
| Braga et al. | Integrating spatial and phylogenetic information in the fourth‐corner analysis to test trait–environment relationships | |
| Moulaire et al. | Temporal dynamics of the scale for the assessment and rating of ataxia in spinocerebellar ataxias | |
| van Oudenhoven et al. | A marginal estimate for the overall treatment effect on a survival outcome within the joint modeling framework | |
| La Rosa et al. | Hypothesis testing of metagenomic data | |
| Landin et al. | Trends in risk factors for readmission after bariatric surgery 2015–2018 | |
| Trifan et al. | Clostridium difficile infection in hospitalized octogenarian patients | |
| Dexter | Checklist for statistical topics in Anesthesia & Analgesia reviews | |
| Liu et al. | Combining models in longitudinal data analysis | |
| Desai et al. | Multiple imputation when rate of change is the outcome of interest | |
| Juarez et al. | The association between body mass index and outcomes in patient with sepsis and acute respiratory failure | |
| Wheeler et al. | Life space assessment in older women undergoing non-surgical treatment for urinary incontinence | |
| Jarynowski et al. | Contact networks and the spread of MRSA in Stockholm hospitals | |
| Sanaei et al. | Designing and implementation of fuzzy expert system for diagnosis of Herpes zoster | |
| Cristaudo et al. | Development and validation of a multivariable prediction model in open abdomen patients for entero‐atmospheric fistula | |
| Carignano et al. | Assessing the effect of unknown widespread perturbations in complex systems using the ν-gap | |
| Chen | A Comparison Between Linear IRT Observed‐Score Equating and Levine Observed‐Score Equating Under the Generalized Kernel Equating Framework | |
| Monleón-Getino et al. | Shannon entropy ratio, a bayesian biodiversity index used in the uncertainty mixtures of metagenomic populations | |
| Srdanov et al. | Counting natural and integer solutions to equations and inequalities |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |