Functionalized Adamantane Tectons Used in the Design of Mixed-Ligand Copper(II) 1,2,4-Triazolyl/Carboxylate Metal–Organic Frameworks

Bistriazoles, 1,3-bis(1,2,4-triazol-4-yl)propane (tr2pr) and 1,3-bis(1,2,4-triazol-4-yl)adamantane (tr2ad), were examined in combination with the rigid tetratopic 1,3,5,7-adamantanetetracarboxylic acid (H4-adtc) platform for the construction of neutral heteroleptic copper(II) metal−organic frameworks. Two coordination polymers, [{Cu4(OH)2(H2O)2}{Cu4(OH)2}(tr2pr)2(H-adtc)4]·2H2O (1) and [Cu4(OH)2(tr2ad)2(H-adtc)2(H2O)2]·3H2O (2), were synthesized and structurally characterized. In complexes 1 and 2, the N1,N2-1,2,4-triazolyl (tr) and μ3-OH− groups serve as complementary bridges between adjacent metal centers supporting the tetranuclear dihydroxo clusters. The structure of 1 represents a unique association of two different kinds of centrosymmetrical {Cu4(OH)2} units in a tight 3D framework, while in compound 2, another configuration type of acentric tetranuclear metal clusters is organized in a layered 3,6-hexagonal motif. In both cases, the {Cu4(OH)2} secondary building block and trideprotonated carboxylate H-adtc3− can be viewed as covalently bound six- and three-connected nodes that define the net topology. The tr ligands, showing μ3- or μ4-binding patterns, introduce additional integrating links between the neighboring {Cu4(OH)2} fragments. A variable-temperature magnetic susceptibility study of 2 demonstrates strong antiferromagnetic intracluster coupling (J1 = −109 cm−1 and J2 = −21 cm−1), which combines for the bulk phase with a weak antiferromagnetic intercluster interaction (zj = −2.5 cm−1).

Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials

OBJECTIVES In 2003 the International Breast Cancer Study Group (IBCSG) initiated the TEXT and SOFT randomized phase III trials to answer two questions concerning adjuvant treatment for premenopausal women with endocrine-responsive early breast cancer: 1-What is the role of aromatase inhibitors (AI) for women treated with ovarian function suppression (OFS)? 2-What is the role of OFS for women who remain premenopausal and are treated with tamoxifen? METHODS TEXT randomized patients to receive exemestane or tamoxifen with OFS. SOFT randomized patients to receive exemestane with OFS, tamoxifen with OFS, or tamoxifen alone. Treatment was for 5 years from randomization. RESULTS TEXT and SOFT successfully met their enrollment goals in 2011. The 5738 enrolled women had lower-risk disease and lower observed disease-free survival (DFS) event rates than anticipated. Consequently, 7 and 13 additional years of follow-up for TEXT and SOFT, respectively, were required to reach the targeted DFS events (median follow-up about 10.5 and 15 years). To provide timely answers, protocol amendments in 2011 specified analyses based on chronological time and median follow-up. To assess the AI question, exemestane + OFS versus tamoxifen + OFS, a combined analysis of TEXT and SOFT became the primary analysis (n = 4717). The OFS question became the primary analysis from SOFT, assessing the unique comparison of tamoxifen + OFS versus tamoxifen alone (n = 2045). The first reports are anticipated in mid- and late-2014. CONCLUSIONS We present the original designs of TEXT and SOFT and adaptations to ensure timely answers to two questions concerning optimal adjuvant endocrine treatment for premenopausal women with endocrine-responsive breast cancer. Trial Registration TEXT: Clinicaltrials.govNCT00066703 SOFT: Clinicaltrials.govNCT00066690.

Design of nest access grids and perches in front of the nests: Influence on the behavior of laying hens.

In aviary systems for laying hens, it is important to provide suitable nest access platforms in front of the nests, allowing hens to reach and explore each of the nests easily. This access platform is needed to achieve good nest acceptance by the hens and thereby prevent mislaid eggs. In the present experiment, the behavior of hens using 2 different nest access platforms, a plastic grid and 2 wooden perches, was examined. Furthermore, the nests were placed on both sides of the aviary rack (corridor side and outdoor side), either integrated into the aviary rack itself (integrated nest; IN) or placed on the walls of the pens (wall nest; WN), resulting in a 2 × 2 factorial design Four thousand five hundred white laying hens were housed in 20 test pens. The eggs in the nests and mislaid eggs were collected daily, and the behavior of hens on the nest accesses was filmed during wk 25 and 26, using focal observation and scan sampling methods. More balancing, body contact, and agonistic interactions were expected for nests with perches, whereas more walking and nest inspections were expected for nests with grids. There were more mislaid eggs and balancing found in pens equipped with nests with wooden perches. More agonistic interactions and balancing, less standing, and a longer duration of nest inspection were found with the WN compared with the IN. Interactions between platform design and position of the nests were found for duration of nest visits, body contact, and walking, with the highest amount for WN equipped with plastic grids. Nests on the corridor side were favored by the hens. Nest-related behaviors, such as nest inspection, standing, and walking, decreased over time as did the number of hens on the nest accesses, whereas sitting increased. These results indicate that the hens had more difficulties in gripping the perches as designed. The lower number of hens on the nest access platforms in front of IN may be due to a better distribution around nests and tier changes within the aviary rack. Based on these results, grids rather than perches provide for improved nesting behavior.

From Caregiver to Computer Geek: The Design of a Web Resource for Novice Clinical Informaticians

Introduction: Throughout the United States, there are massive initiatives in place to reform healthcare through the implementation of electronic health records. The goals are to improve patient care through improved access to records, the improvement of business and reimbursement processes, streamlining of clinician workflows for increased efficiency, and reducing the variability in the delivery of patient care. [See PDF for complete abstract]

Design of SOA services: experiences from industry

Because of the unknown usage scenarios, designing the elementary services of a service-oriented architecture (SOA), which form the basis for later composition, is rather difficult. Various design guide lines have been proposed by academia, tool vendors and consulting companies, but they differ in the rigor of validation and are often biased toward some technology. For that reason a multiple-case study was conducted in five large organizations that successfully introduced SOA in their daily business. The observed approaches are contrasted with the findings from a literature review to derive some recommendations for SOA service design.

The Design of International Trade Agreements: Introducing a New Dataset

Preferential trade agreements (PTAs) have been proliferating for the last twenty years. A large literature has studied various aspects of this phenomenon. Until recently, however, many large-N studies have paid only scant attention to variation across PTAs in terms of content and design. Our contribution to this literature is a new dataset on the design of trade agreements that is the most comprehensive in terms of both variables coded and agreements covered. We illustrate the dataset’s usefulness in re-visiting the questions if and to what extent PTAs impact trade flows. The analysis shows that on average PTAs increase trade flows, but that this effect is largely driven by deep agreements. In addition, we provide evidence that provisions that tackle behind-the-border regulation matter for trade flows. The dataset’s contribution is not limited to the PTA literature, however. Broader debates on topics such as institutional design and the legalization of international relations will also benefit from the novel data.

The FReedom from Ischemic Events-New Dimensions for Survival (FRIENDS) registry: design of a prospective cohort study of patients with advanced peripheral artery disease.

BACKGROUND Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. METHODS/DESIGN The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. DISCUSSION The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD.

Randomized comparison of biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for percutaneous coronary revascularization: Rationale and design of the BIOSCIENCE trial

Background Biodegradable polymers for release of antiproliferative drugs from metallic drug-eluting stents (DES) aim to improve long-term vascular healing and efficacy. We designed a large scale clinical trial to compare a novel thin strut, cobalt chromium DES with silicon carbide coating releasing sirolimus from a biodegradable polymer (Orsiro, O-SES) with the durable polymer-based Xience Prime everolimus-eluting stent (X-EES) in an all-comers patient population. Design The multicenter BIOSCIENCE trial (NCT01443104) randomly assigned 2,119 patients to treatment with biodegradable polymer SES or durable polymer EES at 9 sites in Switzerland. Patients with chronic stable coronary artery disease or acute coronary syndromes, including non-ST-elevation and ST-elevation myocardial infarction, were eligible for the trial if they had at least one lesion with a diameter stenosis >50% appropriate for coronary stent implantation. The primary endpoint target lesion failure (TLF) is a composite of cardiac death, target-vessel myocardial infarction, and clinically-driven target lesion revascularization within 12 months. Assuming a TLF rate of 8% at 12 months in both treatment arms and accepting 3.5% as a margin for non-inferiority, inclusion of 2,060 patients would provide 80% power to detect non-inferiority of the biodegradable polymer SES compared with the durable polymer EES at a one-sided type I error of 0.05. Clinical follow-up will be continued through five years. Conclusion The BIOSCIENCE trial will determine whether the biodegradable polymer SES is non-inferior to the durable polymer EES with respect to TLF.

Risk assessment for the design of a risk-based surveillance programme for fish farms in Switzerland (in accordance with Council Directive 2006/88/EC of the European Union).

Swiss aquaculture farms were assessed according to their risk of acquiring or spreading viral haemorrhagic septicaemia (VHS) and infectious haematopoietic necrosis (IHN). Risk factors for the introduction and spread of VHS and IHN were defined and assessed using published data and expert opinions. Among the 357 aquaculture farms identified in Switzerland, 49.3% were categorised as high risk, 49.0% as medium risk and 1.7% as low risk. According to the new Directive 2006/88/EC for aquaculture of the European Union, the frequency of farm inspections must be derived from their risk levels. A sensitivity analysis showed that water supply and fish movements were highly influential on the output of the risk assessment regarding the introduction of VHS and IHN. Fish movements were also highly influential on the risk assessment output regarding the spread of these diseases.