Bayer Corporation Research Articles

An investigation of blood, milk, and urine test patterns for the diagnosis of ketosis in dairy cows in early lactation.

Ketosis in dairy cattle is primarily diagnosed based on the concentrations of ketone bodies in the blood, milk, or urine. Cow-side tests using these fluids are available for rapid detection of elevated concentrations of ketone bodies. Although these tests have been extensively validated, the performance of different tests has not been compared over time. Our objectives were to investigate the relationship between point-of-care diagnostic tests measuring the concentrations of β-hydroxybutyrate (BHB) in blood (BT; Precision Xtra, Abbott Laboratories), BHB in milk (MT; Keto-Test, Elanco), and acetoacetate (AcAc) in urine (UT; Ketostix, Bayer Corporation) through cases of ketosis. Holstein cows (n = 148) were screened daily for hyperketonemia (HYK; blood BHB ≥1.2 mmol/L) from 3 to 16 d in milk (DIM); moreover, milk and urine samples were collected concomitantly and tested for ketones (ketosis thresholds: 100 µmol/L milk BHB and 5 mg/dL urine AcAc). Of the animals screened (n = 148), 74% were diagnosed with HYK. When diagnosed with HYK, cows were treated with propylene glycol orally once daily for 5 d. After the day of diagnosis (d 0), hyperketonemic cows were retested with BT, MT, and UT for 3 d (d 1, 2, and 3). We assessed the diagnostic test performance and time to ketosis (survival analyses and Cox proportional hazards models) of MT and UT compared with BT. Considering all paired samples (before and after diagnosis of HYK), MT had 61% sensitivity and 91% specificity, whereas the UT had 77% sensitivity and 94% specificity compared with BT. The specificity of MT and UT increased from d 0 to d 1, decreased on d 2, and increased on d 3. The median time to diagnosis of ketosis in blood was 5 DIM (95% CI 5 to 7 DIM); moreover, MT and UT had 2 d greater median time to diagnosis of ketosis compared with the BT [7 DIM (6 to 11 d); and 7 DIM (6 to 13 d), respectively]. We concluded that the UT is a more sensitive predictor of blood BHB concentration than the MT. The UT and MT tests diagnosed ketotic cows approximately 2 d later than the BT. The possible consequences of delay in detection of ketosis in milk and urine should be investigated.

Validation of the biochemical method for determining the total cholesterol level in the samples of biological fluids as a base for providing the quality of dyslipidemia diagnostics

The main principles of creating a quality system in modern laboratory diagnostics are: standardization of laboratory processes by developing standard operating procedures; general quality management of laboratory research based on the development and implementation of the requirements of international standards (according to ISO 15189: 2015 "Medical laboratories. Basic requirements for quality and competence"); quality control of all stages of the laboratory process through the implementation of the validation procedure.
 Aim. To develop a methodology for conducting validation procedures to assess the suitability of a biochemical method for determining the level of total cholesterol in biological fluids in the Clinical Diagnostic Laboratory of the Clinical Diagnostic Center of the NUPh.
 Materials and methods. The object of the study was a standardized method for determining the concentration of total cholesterol. The method was validated using the “Cholesterol Reagent Set” test kit and the standard sample “Chemical control. Reagent kit. Level 1 ", manufactured by High Technology, Inc. (USA) with known concentration. The measurements were carried out on an Express Plus automatic biochemical analyzer manufactured by Bayer Corporation, Germany. When processing the research results, descriptive statistics were used and a number of statistical evaluations were carried out.
 Results. A protocol and a validation report were developed at the Clinical Diagnostic Laboratory of the CDC NUPh to assess the suitability of the method for determining the concentration of cholesterol in biological fluids by the photometric enzymatic method on an automatic biochemical analyzer Express Plus (using reagents and control material manufactured by High Technology, Inc., USA). The validation characteristics of the method were determined: repeatability and reproducibility, correctness and uncertainty of measurements.
 Evaluation of the internal laboratory repeatability and reproducibility of this technique indicates the absence of gross errors in the operation of the instrument and statistically important differences in measurements. The assessment of the correctness of the method (carried out using the control material) proved that the systematic error is not significant (according to a given acceptance criterion). The expanded uncertainty calculation showed that the obtained values ​​of the total cholesterol level can be considered accurate and reliable.
 Conclusions. Validation of the method for determining total cholesterol in human blood by the photometric enzymatic method has proven that this method has performance characteristics that correspond to the regulated ones, meets the established criteria, and the parameters measured with it correspond to the proper ones.
 Key words: validation, determination method, total cholesterol, repeatability and reproducibility, correctness and uncertainty of measurements

Continuing Medical Education and Patient Education on Follicular Lymphoma: Changes in Clinician Practice, Patient Behaviors, and Knowledge across Clinicians and Patients

BACKGROUND: Recent advances on follicular lymphoma (FL) have led to significant changes in disease management. Healthcare providers (HCPs) and their patients face multiple challenges, from treatment initiation, to navigating, selecting and sequencing treatment options while balancing the efficacy and toxicities of available options in the first‐line setting and beyond. To address these needs, in partnership with the Leukemia & Lymphoma Society, we created and measured the impact of continuing medical education (CME) to HCPs and healthcare education directed to patients. METHODS: A 1-hour online video-based CME activity for HCPs and 1-hour healthcare education activity for patients were created in 2018 to address identified practice and knowledge needs among HCPs, and knowledge, communication and self-efficacy behaviors among patients. Each activity consisted of slides, polling and live questions, and were broadcast live and on-demand for 6 months at www.OMedLive.com for HCPs, and CancerCoachLive.com, www.LLS.org and Facebook Video for patients. Test questions were administered at 3 time points (pre-, immediate post-, and 2 mos. post-activity). Data from these test questions, responses to live polling questions, and learner-submitted questions during live Q&A were analyzed to determine engagement, lessons learned and continuing education gaps. RESULTS: As of July 2019, 655 HCPs and 12,198 patients took part in the activities. HCPs reported the activity had a positive impact on patient clinical outcomes (58%) and clinical experience (60%). Significant gains in knowledge/competence were observed in 4 of 8 comparisons (avg. pre-post gain 40.75%, avg. Cohen's d effect size .789) on: immunotherapy, clinical trial data, treatment initiation, and disease progression with immunochemotherapy. With patient learners, 47% reported improved communication with their healthcare providers, 49% increased feeling in control of health care decisions, 40% improved their health-related behaviors, and 17% improved engagement in shared decision making. Significant gains in knowledge were observed in 3 of 8 comparisons (avg. pre-post gain 19.25%, avg. Cohen's d effect size .298) on: treatment for untreated advanced-stage FL, and steps to improve patient care. CONCLUSIONS: CME and patient education can yield gains in clinical practice behaviors, patient healthcare communication and self-efficacy, and treatment knowledge of FL. Together, aligned education directed to HCPs and patients can improve the ability to provide individualized treatment for patients. Continuing education for HCPs is advised on prognostic factors and initial treatment choice for untreated advanced stage FL, post-induction and management strategies for early relapse, emerging agents for FL, and balancing patient desire for therapy where observation is still viable option. For patients, further education is recommended on elements of disease monitoring, pharmacologic and non-pharmacologic treatment options for FL, side effects of therapy, strategies to address relapse, benefits of shared decision-making, and access to specialists and support groups. Disclosures Leonard: Bayer Corporation: Consultancy; Sutro Biopharma: Consultancy; Akcea Therapeutics: Consultancy; Miltenyi: Consultancy; AstraZeneca: Consultancy; Celgene: Consultancy; Epizyme, Inc: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy; Karyopharm Therapeutics: Consultancy; Merck: Consultancy; MorphoSys: Consultancy; Gilead: Consultancy; BeiGene: Consultancy; ADC Therapeutics: Consultancy; Sandoz: Consultancy; Nordic Nanovector: Consultancy.

Subgroup Analyses of Elderly Patients Aged ≥ 70 Years in AUGMENT: A Phase III Randomized Study of Lenalidomide Plus Rituximab (R2) vs Rituximab Plus Placebo (R-Placebo) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL)

Subgroup Analyses of Elderly Patients Aged ≥ 70 Years in AUGMENT: A Phase III Randomized Study of Lenalidomide Plus Rituximab (R2) vs Rituximab Plus Placebo (R-Placebo) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL)

Preliminary Results of a Phase 1 Dose Escalation Study of the First-in-Class Anti-CD74 Antibody Drug Conjugate (ADC), STRO-001, in Patients with Advanced B-Cell Malignancies

Preliminary Results of a Phase 1 Dose Escalation Study of the First-in-Class Anti-CD74 Antibody Drug Conjugate (ADC), STRO-001, in Patients with Advanced B-Cell Malignancies

Potential Factors That Impact Lenalidomide/R-CHOP Efficacy in Previously Untreated Diffuse Large B-Cell Lymphoma in the ROBUST and ECOG-ACRIN 1412 Studies

Potential Factors That Impact Lenalidomide/R-CHOP Efficacy in Previously Untreated Diffuse Large B-Cell Lymphoma in the ROBUST and ECOG-ACRIN 1412 Studies

Approaches to the implementation of the quality system in accordance with ISO 15189:2015 in the Laboratory of Clinical Diagnostics of the Clinical and Diagnostic Center at the National University of Pharmacy on the example of methods for determining the l

A modern clinical and diagnostic laboratory should solve the problems of implementing and maintaining the quality system based on the application of the principles of the specialized standard ISO 15189: 2015 “Medical laboratories. Some requirements for quality and competence” as an element of providing the procedure for assessing the conformity of the laboratory research results. The effective solution of these issues becomes one of the important conditions for accreditation, and the introduction of the assessment of the suitability of methods in daily activities is evidence of the competence of modern clinical and diagnostic laboratories.Aim. To study the approaches to quality assurance in the Clinical Diagnostics Laboratory of the Clinical Diagnostic Center at the NUPh by carrying out validation procedures for assessing the suitability of biochemical methods for determining levels of lactate dehydrogenase (LDH) and glucose in biological fluids.Materials and methods. The objects of the study were standardized biochemical methods for determining levels of LDH and glucose. “Chemical control. Reagent kit. Level1” produced by High Technology, Inc. (USA) with the known concentration of analytes was selected as a control serum. The measurements were performed on an Express Express Plus automatic biochemical analyzer manufactured by Bayer Corporation,Germany. When processing the research results the indicators of descriptive statistics were used, and a number of statistical evaluations were carried out.Results. The procedure for validation of methods consisted of several stages. Protocols and validation reports were developed at the premises of the Clinical Diagnostics Laboratory of theClinicalDiagnosticCenter at the NUPh to assess the suitability of methods for determining LDH and glucose in biological fluids by the photometric method using an Еxpress Рlus biochemical analyzer. Validation was performed using reagents manufactured by High Technology, Inc. (USA) and control materials (standard samples). The following validation characteristics of the methods were determined: specificity, convergence and reproducibility, accuracy, measurement uncertainty. Assessment of the internal laboratory convergence and reproducibility of methods for determining the concentration of LDH and glucose during the operation of the analyzer, which was carried out by two laboratory operators of the same qualification, indicated the absence of gross errors in the operation of the analyzer and statistically important differences in the measurements. Assessment of the correctness of the methods performed using the control serum proved that the systematic error was not significant (according to the given acceptance criterion). Thus, these methods provided correct measurements within the laboratory. The calculation of the expanded uncertainty showed that the values of LDH and glucose levels obtained could be considered accurate and reliable.Conclusions. Validation of methods for determining lactate dehydrogenase and glucose in the human blood by the photometric method has proven that these methods have performance characteristics that meet the regulated and established criteria, and the parameters measured with their help correspond to the proper ones.

Selenium Deficiency in a Mouse Model of Sickle Cell Disease Resulted in Increased Oxygen Consumption and Aberrant Mitochondrial Retention (OR11-05-19)

ObjectivesSickle Cell Disease (SCD) is caused by a single point mutation in the β-globin gene, resulting in the polymerization of the altered hemoglobin βS in hypoxic conditions, affecting millions of people worldwide. Previous studies have shown that there are lower selenium levels and reduced activity of the antioxidant selenoprotein GPX1 in SCD patients. The objective of this study was to investigate the consequences of selenium deficiency in a SCD mouse model. MethodsHumanized SCD (HbSS) mice (Townes model) and wild type (HbAA) mice were purchased from Jackson Laboratories (Bar Harbor, ME). Mice were fed either a selenium-deficient (<0.01 mg/kg) or a selenium adequate (0.1 mg/kg) diet for 4 weeks. Hematological testing was performed using the ADVIATM 120 analyzer (Bayer Corporation, NY). Mitochondrial retention and reactive oxygen species (ROS) were measured by flow cytometry with a BD LSRFortessaTM analyzer using Kaluza analysis software (Beckman Coulter, CA). The oxygen consumption rate (OCR) was measured from isolated red blood cells (RBCs) in real time using the Seahorse Extracellular Analyzer (Agilent, CA). ResultsRBCs normally eject their mitochondria before reaching maturity. However, a previous study demonstrated that there was increased RBC mitochondrial retention in SCD mice and patients when compared to controls. Feeding SCD mice a selenium deficient diet resulted in increased retention of mitochondria in RBCs (26% + 6.9%, 5% + 3.5%, n = 3, P < 0.01), decreased hemoglobin levels (5.7 + 0.17 g/dl, 7.0 + 0.83 g/dl, n = 3, P < 0.05), and an increased OCR of the RBCs (P < 0.01) in these animals when compared to SCD mice fed a selenium adequate diet. ConclusionsProviding humanized SCD mice a selenium deficient diet resulted in increased mitochondrial retention in mature RBCs, decrease hemoglobin levels, and increased RBC oxygen consumption. RBC retention of mitochondria is associated with increased ROS and hemolysis, potentially contributing to the pain and vaso-occlusive crises that occur in the disease. These studies indicate that selenium deficiency may contribute to the severity of symptoms experienced by patients with SCD. Funding SourcesThis work is supported by a grant from the NIH.

Definitive Contraception: Trends in a Ten-year Interval.

Objective To evaluate the trends in definitive contraception in a ten-year interval comprising the years 2002 and 2012. Method Retrospective analysis of the tubal sterilization performed in our service in 2002 and 2012, analyzing the demographic characteristics, personal history, previous contraceptive method, definite contraception technique, effectiveness and complications. Results Definitive contraception was performed in 112 women in 2002 (group 1) and in 60 women in 2012 (group 2). The groups were homogeneous regarding age, parity, educational level and personal history. The number of women older than 40 years choosing a definitive method was more frequent in group 1, 49.1% (n = 55); for group 2, the rate was 34.8% (n = 23) (p = 0.04). The time between the last delivery and the procedure was 11.6 ± 6.2 and 7.9 ± 6.4 years (p = 0.014) in 2002 against 2012 respectively. In 2002, all patients performed tubal ligation by laparoscopic inpatient regime. In 2012, the bilateral placement of the Essure (Bayer Corporation, Whippany, NJ, US) device was suggested to 56.1% (n = 37) of the patients, while laparoscopy was suggested to 43.9% (n = 29) of them. All women who underwent laparoscopic sterilization had the procedure successfully completed using silastic rings. The overall bilateral device placement rate for the Essure was 91.6%, with only one complication reported. All Essure procedures were performed in an outpatient setting; for the laparoscopy, this rate was 79% (n = 15). No intentional pregnancies occurred until this date. Conclusions There is a trend in the decrease in definitive contraception over the years in our institution, maybe as a result of the development of long-acting reversible contraceptives. The hysteroscopic procedure has become a frequent option, as it is performed in an office setting without anesthesia, being a well-tolerated, minimal invasive method.

A Framework of Care in Multiple Sclerosis, Part 2: Symptomatic Care and Beyond.

The Consortium of Multiple Sclerosis Centers (CMSC) convened a Framework Taskforce composed of a multidisciplinary group of clinicians and researchers to examine and evaluate the current models of care in multiple sclerosis (MS). The methodology of this project included analysis of a needs assessment survey and an extensive literature review. The outcome of this work is a two-part continuing education series of articles. Part 1, published previously, covered the updated disease phenotypes of MS along with recommendations for the use of disease-modifying therapies. Part 2, presented herein, reviews the variety of symptoms and potential complications of MS. Mobility impairment, spasticity, pain, fatigue, bladder/bowel/sexual dysfunction, cognitive dysfunction, and neuropsychiatric issues are examined, and both pharmacologic and nonpharmacologic interventions are described. Because bladder and bowel symptoms substantially affect health-related quality of life, detailed information about elimination dysfunction is provided. In addition, a detailed discussion about mental health and cognitive dysfunction in people with MS is presented. Part 2 concludes with a focus on the role of rehabilitation in MS. The goal of this work is to facilitate the highest levels of independence or interdependence, function, and quality of life for people with MS.

Late-Breaking Clinical Trial and Clinical Science Special Reports Abstracts From the American Heart Association's Scientific Sessions 2016; Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2016.

Late-Breaking Clinical Trial and Clinical Science Special Reports Abstracts From the American Heart Association's Scientific Sessions 2016; Late-Breaking Abstracts in Resuscitation Science From the Resuscitation Science Symposium 2016.

Targeted Inhibition of Activated Protein C Anticoagulant Activity By Monoclonal Antibody HAPC1573 for Treatment of Hemophilia

In patients with hemophilia, hereditary defects in coagulation factors result in unstable clots and recurrent bleeding. Although the current standard of care focuses on replacement factor therapy, we propose that inhibition of the anticoagulant pathways may offer novel therapeutic opportunities. Activated protein C (APC) is one of the major anticoagulants, which works by degrading factors Va and VIIIa to maintain hemostatic balance. APC also exhibits cytoprotective effects, which include antiapoptotic effects, endothelial barrier protection, and anti-inflammatory effects. Antibodies are ideally suited to inhibit the anticoagulant activity of APC while preserving its cytoprotective activity.We have developed an anti-APC monoclonal antibody (mAb), HAPC1573 (murine immunoglubulin G1/kappa), using hybridoma technology, that specifically binds to human APC (hAPC) at 3 to 7 nM binding affinity (Kd) but not to its zymogen, protein C (PC) as determined by surface plasmon resonance (SPR) using a Biacore T200 instrument (GE Healthcare, Pittsburgh, PA). To investigate the binding epitope of mAb HAPC1573, APC was inhibited with Phe-Pro-Arg-chloromethylketone (PPACK). PPACK is an irreversible inhibitor of APC and forms a covalent bond with the catalytic triad Ser195 (chymotrypsin numbering).HAPC1573 bound comparably to PPACK-hAPC and untreated hAPC coated on an enzyme-linked immunosorbent assay (ELISA) plate, suggesting that the binding epitope of HAPC1573 is located outside the active site of APC. These ELISA results were also confirmed by SPR analyses. HAPC1573 inhibited the cleavage of a small peptide substrate Spectrozyme PCa (Sekisui Diagnostics, Lexington, MA) by hAPC up to 40%. The antibody protected factors Va and VIIIa from APC-mediated inactivation in a dose-dependent manner. HAPC1573 significantly reduced activated partial thromboplastin time of hemophilic plasma and enhanced thrombin generation (assessed by thrombin generation assay) in the presence of thrombomodulin. HAPC1573 inhibited the anticoagulant activity of APC without affecting its cytoprotective functions, as measured by histone-mediated cytotoxicity assays on human umbilical vein endothelial cells (up to 300 nM HAPC1573). Given its cross-reactivity with monkey APC, the antibody was evaluated in Cynomolgus monkeys for therapeutic efficacy and safety. Intravenous administration of the antibody at 3 and 10 mg/kg significantly shortened bleeding time after injury and restored hemostasis in a dose-dependent manner in an anti-FVIII antibody-induced hemophilia monkey model (Figure). Administration of a sheep-anti-FVIII antibody (Haematologic Technologies, Inc., Essex Junction, VT) reduced plasma FVIIIa activity to below the lower limit of quantification (LLOQ; Figure [left panel]) and led to a significantly longer bleeding time in normal monkeys (Figure; right panel), recapitulating the hemophilia A phenotype. This prolonged bleeding time was partially reduced by 270 µg/kg of recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Plainsboro, NJ) used as a positive control for these studies. There was a statistically significant dose-dependent reduction in bleeding time by HAPC1573 with the 10-mg/kg dose restoring the bleeding time back to normal.This study provides in vivo proof of concept of using anti-APC antibody for hemophilia. HAPC1573 represents an anti-APC antibody with therapeutic utility for patients with hemophilia with inhibitors. [Display omitted] DisclosuresZhao:Bayer Pharmaceuticals: Employment. Yegneswaran:Bayer Healthcare Pharmaceuticals: Employment. Sim:Bayer: Employment. Patel:Bayer Pharmaceuticals: Employment. Schneider:Bayer HealthCare LLC: Employment, Patents & Royalties. McLean:Bayer: Employment, Equity Ownership. Zhu:Bayer Healthcare: Employment. Jiang:Bayer Pharmaceuticals: Employment. Gu:Bayer Pharmaceuticals: Employment. Ivens:Bayer Pharmaceuticals: Employment. Xu:Shanghai RAAS Blood Products Co.Lt: Employment, Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties: Patent. Bringmann:Bayer Corporation, Parmaceuticals Division: Employment. Kauser:Bayer: Employment.

CME/CNE Article: A Framework of Care in Multiple Sclerosis, Part 1: Updated Disease Classification and Disease-Modifying Therapy Use in Specific Circumstances.

CME/CNE Article: A Framework of Care in Multiple Sclerosis, Part 1: Updated Disease Classification and Disease-Modifying Therapy Use in Specific Circumstances.

Comparative Evaluation of Ciprofloxacin Levels in GCF and Plasma of Chronic Periodontitis Patients: Quasi Experimental Study.

For any antimicrobial approach to be successful in periodontal therapy, it is important that the antimicrobial agent targets the sub-gingival biofilm by attaining sufficient concentration at the sub-gingival site. The purpose of the present study was to determine and compare the concentrations of ciprofloxacin present in Gingival Crevicular Fluid (GCF) and plasma after its systemic administration. A total of 20 subjects, in the age group of 30-60 years satisfying the inclusion and exclusion criteria, were chosen from the outpatient Department of Periodontology, Government Dental College and Hospital, Hyderabad and consent was obtained. Subjects were put on oral ciprofloxacin therapy (Baycip, Bayer Corporation) of 500mg twice daily doses for five days to establish steady state tissue levels of the agent. GCF and serum samples were collected at the 72(nd) hour after the first dose of ciprofloxacin and were compared using unpaired t test. The mean gingival index value of the subjects was 1.8 ± 0.59 and the mean probing depth of the subjects taken in the study was 5.724 ± 0.47mm. The results of this study showed that ciprofloxacin concentrations were significantly higher (p<0.001) in GCF than in plasma. Results from the present study and those from the earlier studies clearly indicate the ciprofloxacin's ability to reach and concentrate in infected periodontal sites via GCF. This property of ciprofloxacin may be useful for eradication of periodontal pathogens, thus improving the outcome of periodontal therapy.

Expanding the reach of India's ‘Bolar’ exemption

In November 2014, the scope of the regulatory review exemption contained in section 107A(a) of the Indian Patents Act was considered by the Delhi High Court in the case of Bayer Corporation v Union of India. In this case, which is a sequel to the compulsory license that was earlier granted to Natco in respect of Bayer's patented drug in 2012, Natco sought to export 1 kilogramme of the patented active pharmaceutical ingredient to a company in China. Bayer contended that this was in breach of the terms of the compulsory license and equally outside the scope of section 107A(a). Natco however argued for a broader interpretation of section 107A(a) in a manner that will permit the exportation of patented active pharmaceutical ingredients to producers of generic drugs solely for the purposes of generating information required for obtaining regulatory approval. In accepting Natco's broader interpretation of section 107A(a), the Delhi High Court incorporated a model of human rights into its decision by being mindful of the implications that a restrictive interpretation of section 107A(a) could have on the production of cheaper generic drugs and access to medicines. This decision reinforces India's crucial position as the ‘pharmacy of the developing world’.

Building national initiatives of compulsory licences

Purpose– The purpose of this paper is to examine the extent to which developing countries could build national initiatives of compulsory licences.Design/methodology/approach– The focus of this article is only on developing countries. The author reflects on the Indian patent jurisprudence regarding the operational relationship between the general principles applicable to working of patented inventions locally and the grant of compulsory licences. The discussion that follows is based on a review of the case: Bayer Corporation versus Natco Pharma with a view to presenting a model for developing countries to maintain that the public interest principle of patent law is well-founded in their domestic patent regimes.Findings– The analysis confirms that failure to work locally continues to be abusive of the patent right under the Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement, and remains a valid condition on which to grant a compulsory licence. Thus, this reverses the often-contrary misconception that has become almost a unanimous assumption that failure to work basis for granting compulsory licensing would violate Article 27(1) of TRIPS and its enforcement provisions on patent.Originality/value– The author argues that as no member state has challenged the legality of Indian’s decision in the World Trade Organisation, under the dispute settlement understanding (DSU) system is more supportive of the contention that failure to work locally continues to be permissible under TRIPS and remains valid conditions on which member states can grant compulsory licences. This further adds weight to the understanding that nothing in the light of TRIPS would, in fact, preclude any possibility of developing countries amending their patent laws accordingly to maintain that the public interest principle underlining patent law is well-founded in their domestic patent regimes.

Long-Term Efficacy of Various Natural or "Green" Insecticides against Bed Bugs: A Double-Blind Study.

Bed bugs are resurging throughout the world, and, thus, effective pest control strategies are constantly needed. A few studies have evaluated 25(b) and other natural, or so-called “green” products, as well as over-the-counter insecticides for bed bugs, but additional studies are needed to determine efficacy of bed bug control products. This double-blinded research project was initiated to examine long-term effectiveness of six commercially available natural or “green” insecticides against bed bugs and to compare them with three known traditional residual products. Water was used as a control. Products were evaluated against both susceptible and resistant strains of bed bugs (1200 bugs each), and two different substrates were used. Temprid® (Bayer Corporation, Monheim, Germany), Transport® (FMC Corp., Philadelphia, PA, USA), Invader® (FMC Corporation, Philadelphia, PA USA), Cimexa® (Rockwell Laboratories, Kansas City, MO, USA), and BBT-2000® (Swepe-Tite LLC, Tupelo, MS, USA) were the only products which showed any substantial (>40%) bed bug control upon exposure to treated substrates after the six-month waiting period, although results with the resistant bed bug strain were much reduced. Alpine dust® (BASF Corporation, Florham Park, NJ, USA) killed 27% of bed bugs or less, depending on strain and substrate. EcoRaider® (North Bergen, NJ, USA) and Mother Earth D® (Whitmire Microgen, Florham Park, NJ, USA) (diatomaceous earth) produced 11% control or less. Cimi-Shield Protect® (Pest Barrier, Carson, CA, USA) showed no activity against bed bugs in this study. Analysis using SAS software showed a three-way interaction between treatment, substrate, and bed bug strain (Numerator DF 9; Denominator DF 80; F = 4.90; p < 0.0001).

Validation of two diagnostic methods for postpartum endometritis in dairy cows

Postpartum uterine diseases can impair reproductive performance of dairy cows. Diagnostic tools have been developed to identify cows at risk of poor subsequent reproductive performance. Most of these tools focus on identification of inflammation in the reproductive tract during the postpartum period. Endometrial cytology was proposed as a good tool to identify cows with cytological endometritis; however, cytology is not an easy technique to implement for an on-farm uterine health surveillance program in dairy herds because it requires the use of a microscope. Therefore, a more convenient on-farm method needs to be identified for determination of uterine status of dairy cows. Aleucocyte esterase (LE) colorimetric test is commercially available (Multistix®, Bayer Corporation, Elkhart, IN) and could be used to detect endometrial inflammation. The objectives of this study were to determine diagnostic criteria for endometritis in dairy cows by use of endometrial cytology and LE testing, to quantify the agreement between results of these two methods, and to quantify their impact on subsequent reproductive performance.

Confirmatory Testing of Urine Ketones and Bilirubin: Still Necessary?

To the Editor.—Urinalysis is a useful tool in diagnosis, screening, and monitoring the progress of diseases.1 However, laboratory practice is inconsistent in the use of urine confirmatory tests for the presence of ketones and bilirubin in urine. Thus, we recently conducted a study and intended to standardize this issue.Urine ketone level was measured using a nitroprusside reaction and bilirubin was measured by the diazo method on an Aution Max AX-4280 automated urine chemistry analyzer (Iris Diagnostics, Chatsworth, California). Urine ketones were confirmed with Acetest and bilirubin was confirmed with Ictotest (Bayer Corp, Elkhart, Indiana). Of 492 urine samples analyzed for ketones on the AX-4280, 42 (8.54%) were positive for ketones. Acetest confirmed 35 of the 42 ketone-positive samples as ketone positive (Table). Most of the discrepancies between urinalysis and Acetest results were seen at 10 mg/dL on the AX-4280. Of 4270 urine samples analyzed for bilirubin on the AX-4280, 108 samples were positive for bilirubin (2.53%) and 107 of those samples were confirmed to be bilirubin positive by Ictotest (Table).A survey was also conducted showing that 13 of the 25 responding laboratories were still doing confirmatory testing for bilirubin by Ictotest (52%). Similarly, 2 of 8 responding laboratories were still using Acetest to confirm urine ketones.The confirmatory testing was historically performed to confirm results obtained from the urine dipstick. Substantial improvements in the sensitivity and specificity of automated semiquantitative analyzers have dramatically reduced the necessity of confirmatory testing. We believe that there is no rationale for continuing these confirmatory tests, for the following reasons:In summary, using the same or a similar qualitative methodology to confirm another qualitative method duplicates work, increases costs, and may provide misleading information. Thus, such confirmatory tests should be discontinued. Confirmatory and complementary tests such as serum bilirubin and ketones (in particular β-hydroxybutyrate) should be ordered when clinically warranted.

Restraining Multiple Bites at the Class Certification Apple: May a Federal Court Enjoin a State Court from Relitigating a Class Certification Denial?

This article previews the issues and arguments in the 2010-11 Supreme Court Term case, Smith v. Bayer Corp. In 2001, Keith Smith and Shirley Sperlazza filed a class action lawsuit against Bayer Corporation in West Virginia state court, alleging varying claims arising out of their use of the prescription drug Baycol. In 2008, the Federal District Court for Minnesota, overseeing the massive Baycol products multidistrict litigation, denied class certification under the federal class action Rule 23, to a proposed class of West Virginia consumers alleging economic-loss injury. Shortly after denial of the federal action, the Smith class moved for class certification in state court pursuant to the West Virginia class action rule.In response, the Bayer Corporation sought a permanent injunction enjoining the West Virginia class certification hearing, which the Minnesota federal district court granted. In January 2010, the United States Court of Appeals for the Eighth Circuit upheld this federal injunction of the West Virginia class certification hearing. This appeal involves the issue whether a federal court, consistent with the All Writs Act and the Anti-Injunction Act, could enjoin the West Virginia state court from determining whether to certify a class action after a federal court previously denied class certification in a virtually identical class action.The Court will address two major issues: (1) When a federal court in an MDL proceeding denies class certification of a statewide class action, may the court pursuant to the All Writs Act and the Anti-Injunction Act enjoin putative class members who were represented in the federal hearing from seeking class certification in state court for the same class action?, and (2) When a federal court in an MDL proceeding denies class certification of a statewide class action, is it impermissible for the federal court to issue an injunction restraining absent class member from seeking state class certification, where those absent class members were not afforded the due process protections required if certification had been granted?In deciding the Smith appeal, the Supreme Court will not forge any new ground in interpreting the Anti-Injunction Act or the All Writs Act. The appeal basically presents a fairly straightforward question concerning the appropriate exercise of the relitigation exception, in the context of dual federal-state class action practice. However, the Court’s Smith decision will have important implications for federal and state class action litigation.In the past twenty years, burgeoning of class action litigation in both federal and state court has given rise to problems relating to intersystem adjudication of complex litigation. There are no legal restrictions on litigants from filing parallel actions in both federal and state court, and the Anti-Injunction Act is a relatively weak mechanism for restraining parallel state proceedings.In the past two decades, federal courts have attempted to better manage duplicative class action litigation through increased use of the MDL procedures, which enable consolidation of all similar cases throughout the federal system, for coordinated pre-trial discovery and other proceedings. MDL procedure has proved to be a very effective mechanism for resolving massive litigation. In addition, Congress manifested an interest in channeling class action litigation into federal courts by enactment of CAFA, which created new federal jurisdiction for class actions and provided a vehicle for removal of class actions from state court into the federal system.Notwithstanding these developments, litigants still may pursue class action relief under state class action rules. The Smith appeal confronts the Court with the important question whether state litigants are free to seek a different class certification decision in a state court, once a federal court has determined class certification is not appropriate, and should be denied. As Bayer suggests, such a ruling would provide litigants with an incentive to keep filing state class actions until they find a judge who decides differently than the federal court. For policy reasons alone, Bayer contends this is an untenable conclusion.The Smith plaintiffs, on the other hand, suggest this case tests the very heart of federalism: the notion that state courts are free to determine issues according to their own interpretation of their laws and procedures, even where those laws and procedures are identical to federal rules.In the end, the Court’s opinion is likely to turn on a careful, nuanced analysis of the requirements of preclusion doctrine, with careful attention to the parties, issues, and nature of the class proceedings. We also may expect the Court to supply some further elucidation of what due process requires, in the class action context, to give preclusive effect to a class certification denial to nonparties to a prior litigation.