The Global Employer: The Labor Relations and Collective Agreements Issue

[Excerpt] Baker & McKenzie’s Global Employment Practice Group is pleased to present its 56th issue of The Global Employer™ entitled “The Labor Relations and Collective Agreements Issue.” In this issue you will find the first report from our Future of Work Series. Labor Relations Report - Brand Attack: How to avoid becoming the target of a corporate campaign and what actions to take if you do. The Future of Work is a series of client reports based on panel discussions at our Global Employer Forum, a two-day thought leadership conference. During the forum, nearly 70 clients, academics and consultants gathered with our employment partners to discuss pressing workplace topics like talent shortages, data privacy, global mobility assignments, globalization of unions and managing the employment aspects of M&A deals. Rather than the traditional “how to” legal format of most law firm conferences, the Global Employer Forum features panel discussions of in-house counsel and senior-level executives from some of the world’s largest multinational organizations who discussed their personal experiences addressing these challenges and the solutions they have found to overcome them. Following the Labor Relations Report, you will also find information pertaining to the current state of labor relations and union negotiations in Argentina and a general overview of the current state of collective bargaining in Brazil. In Germany, we take a look at some of the numbers behind collective bargaining agreements; and a review of the impacts on labor benefits of the January 2014, Income Tax Law reform in Mexico. From Spain we bring you articles that discuss negotiating with representatives bodies in collective lay-offs and the new role of company level collective bargaining agreements; and from the US, recent efforts by the NLRB as it Targets Successor Issues in US Mergers and Acquisitions

The Global Employer: The Employment Law Review and Reform Issue

[Excerpt] Although the economies of many jurisdictions are improving, there is still some lingering global economic uncertainty. It is no surprise that governments the world over continue to revisit their employment laws to see what else, if anything, can be done to further stimulate their economies. 2013 was another busy year for employment law reform. Baker & McKenzie’s Global Employment Practice Group is pleased to present its 55th issue of The Global Employer™ entitled “The Employment Law Review and Reform Issue.” In this issue, we review changes to the law in 2013 and a look at pending changes for 2014. Included, you will find information pertaining to the leasing of employees in Germany; new measures in Spain intended to promote employment among young people under 30 and employee privacy rights over employers\u27 controls; challenges to the applicable interest rate to worker\u27s claims in Argentina; how employment law reforms will significantly impact employers in Mexico and in some specific cases, may considerably elevate increase the cost of formal employment; and controversy around making the Colombian Social Security System more progressive. We also review several significant legal developments in China during 2013 that impact employers operating there; legislative changes that were expected in Hong Kong in 2013 that may be implemented in 2014 including a focus on discrimination in the coming years; and welcome changes to TUPE and automatic pension plan enrollment in the United Kingdom

Multi-layered collagen-based scaffolds for osteochondral defect repair in rabbits.

INTRODUCTION: Identification of a suitable treatment for osteochondral repair presents a major challenge due to existing limitations and an urgent clinical need remains for an off-the-shelf, low cost, one-step approach. A biomimetic approach, where the biomaterial itself encourages cellular infiltration from the underlying bone marrow and provides physical and chemical cues to direct these cells to regenerate the damaged tissue, provides a potential solution. To meet this need, a multi-layer collagen-based osteochondral defect repair scaffold has been developed in our group. AIM: The objective of this study was to assess the in vivo response to this scaffold and determine its ability to direct regenerative responses in each layer in order to repair osteochondral tissue in a critical-sized defect in a rabbit knee. METHODS: Multi-layer scaffolds, consisting of a bone layer composed of type I collagen (bovine source) and hydroxyapatite (HA), an intermediate layer composed of type I and type II collagen and HA; and a superficial layer composed of type I and type II collagen (porcine source) and hyaluronic acid (HyA), were implanted into critical size (3 × 5 mm) osteochondral defects created in the medial femoral condyle of the knee joint of New Zealand white rabbits and compared to an empty control group. Repair was assessed macroscopically, histologically and using micro-CT analysis at 12 weeks post implantation. RESULTS: Analysis of repair tissue demonstrated an enhanced macroscopic appearance in the multi-layer scaffold group compared to the empty group. In addition, diffuse host cellular infiltration in the scaffold group resulted in tissue regeneration with a zonal organisation, with repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark. CONCLUSION: These results demonstrate the potential of this biomimetic multi-layered scaffold to support and guide the host reparative response in the treatment of osteochondral defects. STATEMENT OF SIGNIFICANCE: Osteochondral defects, involving cartilage and the underlying subchondral bone, frequently occur in young active patients due to disease or injury. While some treatment options are available, success is limited and patients often eventually require joint replacement. To address this clinical need, a multi-layer collagen-based osteochondral defect repair scaffold designed to direct host-stem cell mediated tissue formation within each region, has been developed in our group. The present study investigates the in vivo response to this scaffold in a critical-sized defect in a rabbit knee. Results shows the scaffolds ability to guide the host reparative response leading to tissue regeneration with a zonal organisation, repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark

Anterior cruciate ligament reconstruction with bone-patellar tendon-bone autograft versus allograft in young patients

Objectives: Traditionally, bone-patella tendon-bone (BTB) autograft has been the gold standard graft choice for younger, athletic patients requiring ACL reconstruction. However, donor site morbidity, post-operative patella fracture, and increased operative time have led many surgeons to choose BTB allograft for their reconstructions. Opponents of allografts feel that slower healing time, higher rate of graft failure, and potential for disease transmission makes them undesirable graft choices in athletic patients. The purpose of this study is to evaluate the clinical outcomes, both subjective and objective, of young patients that who have undergone either BTB autograft or allograft reconstructions with a minimum of 2-year follow-up. Methods: One hundred and twenty patients (60 autograft, 60 allograft), age 25 and below at time of surgery, were contacted after being retrospectively identified as patients having an ACL reconstruction with either a BTB allograft or autograft by one senior surgeon. Patients were administered the Lysholm Knee Scoring Scale and IKDC Subjective Knee Evaluation questionnaires. Fifty (25 BTB autograft and 25 BTB allograft) of the 120 returned for physical examination as well as completion of a single leg hop test and laxity evaluation using a KT-1000 arthrometer evaluation. Of the 120 patients contacted, there were a total of 7 failures (5.8%) requiring revision, 6 in the allograft group (86%) and 1 in the autograft group (14%). Results: The average Lysholm scores were 89.0 and 89.56 and the average IKDC scores were 90.8 and 92.1 in the autograft and allograft groups respectively. The differences in the Lysholm scores and the IKDC scores were not significant. The single leg hop and KT-1000 scores were also not significantly different. One autograft patient had a minor motion deficit. Three allograft patients had a grade 1 Lachman and pivot glide. One autograft patient and two allograft patients had mild patellafemoral crepitus. There was no significant difference in anterior knee pain between the two groups Conclusion: There is no significant difference in patient-rated outcome between ACL reconstructions using BTB autografts versus allografts. However, the overall study group did reveal an increased failure rate requiring revision in the allograft group. © The Author(s) 2015

The effect of pore size on permeability and cell attachment in collagen scaffolds for tissue engineering.

The permeability of scaffolds and other three-dimensional constructs used for tissue engineering applications is important as it controls the diffusion of nutrients in and waste out of the scaffold as well as influencing the pressure fields within the construct. The objective of this study was to characterize the permeability/fluid mobility of collagen-GAG scaffolds as a function of pore size and compressive strain using both experimental and mathematical modeling techniques. Scaffolds containing four distinct mean pore sizes (151, 121, 110, 96 microns) were fabricated using a freeze-drying process. An experimental device was constructed to measure the permeability of the scaffold variants at different levels of compressive strain (0, 14, 29 and 40% while a low-density open-cell foam cellular solids model utilizing a tetrakaidecahedral unit cell was used to accurately model the permeability of each scaffold variant at all level of applied strain. The results of both the experimental and the mathematical analysis revealed that scaffold permeability increases with increasing pore size and decreases with increasing compressive strain. The excellent comparison between experimentally measured and predicted scaffold permeability suggests that cellular solids modelling techniques can be utilized to predict scaffold permeability under a variety of physiological loading conditions as well as to predict the permeability of future scaffolds with a wide variety of pore microstructures

Gene expression by marrow stromal cells in a porous collagen-glycosaminoglycan scaffold is affected by pore size and mechanical stimulation.

Marrow stromal cell (MSC) populations, which are a potential source of undifferentiated mesenchymal cells, and culture scaffolds that mimic natural extracellular matrix are attractive options for orthopaedic tissue engineering. A type I collagen-glycosaminoglycan (CG) scaffold that has previously been used clinically for skin regeneration was recently shown to support expression of bone-associated proteins and mineralisation by MSCs cultured in the presence of osteogenic supplements. Here we follow RNA markers of osteogenic differentiation in this scaffold. We demonstrate that transcripts of the late stage markers bone sialoprotein and osteocalcin are present at higher levels in scaffold constructs than in two-dimensional culture, and that considerable gene induction can occur in this scaffold even in the absence of soluble osteogenic supplements. We also find that bone-related gene expression is affected by pore size, mechanical constraint, and uniaxial cyclic strain of the CG scaffold. The data presented here further establish the CG scaffold as a potentially valuable substrate for orthopaedic tissue engineering and for research on the mechanical interactions between cells and their environment, and suggest that a more freely-contracting scaffold with larger pore size may provide an environment more conducive to osteogenesis than constrained scaffolds with smaller pore sizes

miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation of leukemic blasts, and induced cell death. Antagonism of miR-196b activity or pharmacologic inhibition of the Cks1-Skp2–containing SCF E3-ubiquitin ligase complex increased p27Kip1 and inhibited human AML growth. This work illustrates that understanding oncogenic miRNA target pathways can identify actionable targets in leukemia

Mechanistic interrogation of combination Bevacizumab/dual PI3K/mTOR inhibitor response in Glioblastoma implementing novel MR and PET imaging biomarkers.

Purpose: Resistance to bevacizumab (BEV) in glioblastoma (GBM) is believed to occur via activation of molecular networks including the mTOR/PI3K pathway. Implementing an MRI/PET molecular imaging biomarker approach, we sought to interrogate response to combining BEV with the mTOR/PI3K inhibitor BEZ235. Methods: Tumors were established by orthotopically implanting U87MG-luc2 in mice. Animals were treated with BEZ235 and/or BEV, and imaged using diffusion weighted-MRI, T2 weighted (T2w), and T2* weighted (T2*w) before and following delivery of superparamagnetic iron oxide (SPIO) contrast. Maps for changes in relaxation rates: ΔR2, ΔR2* and apparent diffusion coefficient (ADC) were calculated. Vessel Size Index (VSI) and micro vessel density index (MDI) were derived. 3´-deoxy-3´-[18F]fluorothymidine ([18F]FLT)- and O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) PET was further performed and tumor endothelium/proliferation markers assessed by immunohistochemistry. Results: Treatment with BEV resulted in a pronounced decrease in tumor volume (T2w MRI). No additive effect on tumour volume was observed in BEV/BEZ235 combination compared with BEV monotherapy. Ki67 proliferation index staining and [18F]FLT uptake studies were used to support observations. Using ΔR2* and ΔR2 values respectively, BEZ235 + BEV combination significantly reduced tumor microvessel volume in comparison to BEV alone. Decreased MDI was further observed in the combination group; supported by von Willebrand Factor (vWF) immunohistochemistry. We observed decreased [18F]FET uptake following BEV, but failed to observe further reduced [18F]FET uptake in the combination cohort. vWF IHC analysis showed mean tumor vessel size increased in all cohorts. Conclusions: Assessing MR imaging biomarker parameters together with [18F]FET and [18F]FLT PET, informed drug combination mechanism of action and provided clues as to potential clinical response. Translation of a BEZ35/BEV combination regimen could support reduction of peritumoral edemaobviating the requirement for steroids. Implementing hypothesis driven molecular imaging studies facilitates the interrogation of drug response in the pre-clinic. These data may more accurately predict the clinical potential of novel therapeutic approaches in oncology