On Chemical Bonding in ht-Ga3Rh and Its Effect on Structural Organization and Thermoelectric Behavior.

In the course of systematic studies of intermetallic compounds Ga3TM (TM─transition metal), the compound Ga3Rh is synthesized by direct reaction of the elements at 700 °C. The material obtained is characterized as a high-temperature modification of Ga3Rh. Powder and single-crystal X-ray diffraction analyses reveal tetragonal symmetry (space group P42/mnm, No. 146) with a = 6.4808(2) Å and c = 6.5267(2) Å. Large values and strong anisotropy of the atomic displacement parameters of Ga atoms indicate essential disorder in the crystal structure. A split-position technique is applied to describe the real crystal structure of ht-Ga3Rh. Bonding analysis in ht-Ga3Rh performed on ordered models with the space groups P1̅, P42nm, and P42212 shows, besides the omnipresent heteroatomic Ga-Rh bonds in the rhombic prisms ∞3[Ga8/2Rh2], the formation of homoatomic Ga-Ga bonds bridging the Rh-Rh contacts and the absence of significant Rh-Rh bonding. These features are essential reasons for the experimentally observed disorder in the lattice. In agreement with the calculated electronic density of states, ht-Ga3Rh shows temperature-dependent electrical resistivity of a "bad metal". The very low lattice thermal conductivity of less than 0.5 W m-1 K-1 at 300 K, being lower than those for most other Ga3TM compounds, correlates with the enhanced bonding complexity.

Dose escalation randomised study of efmarodocokin alfa in healthy volunteers and patients with ulcerative colitis.

BACKGROUND: The interleukin-22 cytokine (IL-22) has demonstrated efficacy in preclinical colitis models with non-immunosuppressive mechanism of action. Efmarodocokin alfa (UTTR1147A) is a fusion protein agonist that links IL-22 to the crystallisable fragment (Fc) of human IgG4 for improved pharmacokinetic characteristics, but with a mutation to minimise Fc effector functions. METHODS: This randomised, phase 1b study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of repeat intravenous dosing of efmarodocokin alfa in healthy volunteers (HVs; n=32) and patients with ulcerative colitis (n=24) at 30-90 µg/kg doses given once every 2 weeks or monthly (every 4 weeks) for 12 weeks (6:2 active:placebo per cohort). RESULTS: The most common adverse events (AEs) were on-target, reversible, dermatological effects (dry skin, erythema and pruritus). Dose-limiting non-serious dermatological AEs (severe dry skin, erythema, exfoliation and discomfort) were seen at 90 µg/kg once every 2 weeks (HVs, n=2; patients, n=1). Pharmacokinetics were generally dose-proportional across the dose levels, but patients demonstrated lower drug exposures relative to HVs at the same dose. IL-22 serum biomarkers and IL-22-responsive genes in colon biopsies were induced with active treatment, and microbiota composition changed consistent with a reversal in baseline dysbiosis. As a phase 1b study, efficacy endpoints were exploratory only. Clinical response was observed in 7/18 active-treated and 1/6 placebo-treated patients; clinical remission was observed in 5/18 active-treated and 0/6 placebo-treated patients. CONCLUSION: Efmarodocokin alfa had an adequate safety and pharmacokinetic profile in HVs and patients. Biomarker data confirmed IL-22R pathway activation in the colonic epithelium. Results support further investigation of this non-immunosuppressive potential inflammatory bowel disease therapeutic. TRIAL REGISTRATION NUMBER: NCT02749630.

Polycation-Polyanion Architecture of the Intermetallic Compound Mg3-xGa1+xIr.

Mg3-xGa1+xIr (x = 0.05) was synthesized by direct reaction of the elements in welded tantalum containers at 1200 °C and subsequent annealing at 500 °C for 30 days. Its crystal structure represents a new prototype and was determined by single-crystal technique as follows: space group P63/mcm, Pearson symbol hP90, Z = 18, a = 14.4970(3) Å, c = 8.8638(3) Å. The composition and atomic arrangement in Mg3GaIr do not follow the 8-N rule due to the lack of valence electrons. Based on chemical bonding analysis in positional space, it was shown that the title compound has a polycationic-polyanionic organization. In comparison with other known intermetallic substances with this kind of bonding pattern, both the polyanion and the polyanion are remarkably complex. Mg3-xGa1+xIr is an example of how the general organization of intermetallic substances (e.g., formation of polyanions and polycations) can be understood by extending the principles of 8-N compounds to electron-deficient materials with multi-atomic bonding.

Beam quality and efficiency of ns-pulsed high-power mid-IR ZGP OPOs compared in linear and non-planar ring resonators.

We compare the performance of ns-pulsed mid-infrared optical parametric oscillators (OPOs) based on ZGP crystals in a simple linear cavity and two non-planar image-rotating resonators. Our 2 µm pump source is a 68 W 10 kHz diffraction limited Ho:LLF MOPA system. In a linear cavity, it allows us to generate up to 38 W of the total average power with M2<2.2 from the ZGP OPO in the 3-5 µm range. Beam quality and stability are significantly improved in both types of non-planar ring resonators (M2<1.8 in RISTRA and M2<1.4 in FIRE), while the total average power is above 21 W. Factors influencing the beam quality such as average power and pump repetition rate are studied in detail.

Licogliflozin versus placebo in women with polycystic ovary syndrome: A randomized, double-blind, phase 2 trial.

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and insulin resistance. The dual sodium-glucose co-transporter 1/2 inhibitor (SGLT1/2i) licogliflozin (LIK066) ameliorates hyperinsulinism in patients with diabetes and obesity. This study examines the effect of licogliflozin on androgens in women with PCOS. In a multicentre, randomized, placebo-controlled, double-blind, 2-week trial, patients with PCOS received licogliflozin 50 mg or placebo three times a day (TID). Changes in free testosterone (FT), other androgens and variables of insulin resistance were analysed. Concentration of FT did not change (TRLIK066 :TRPCB [FT]: 0.88; 90% CI: 0.70-1.11; P = .353). Licogliflozin reduced androstendione (A4) by 19% (TRLIK066 :TRPCB [A4]: 0.81; 90% CI: 0.68-0.99; P = .089) and dehydroepiandrosteron sulphate (DHEAS) by 24% (TRLIK066 :TRPCB [DHEAS]: 0.76; 90% CI: 0.65-0.89; P = .008). Hyperinsulinaemia was reduced by 70% by licogliflozin (highest insulin concentration [MAXI]; TRLIK066 :TRPCB [MAXI]: 0·26; 90% CI:0.20-0.34; P < .001 and area under the curve insulin [AUCI]; TRLIK066 :TRPCB [AUCI]: 0.32; 90% CI: 0.25-0.41; P < .001). Diarrhoea and nausea occurred as common adverse events. Dual inhibition of SGLT1/2 ameliorates hyperinsulinaemia and hyperandrogenaemia in women with PCOS. Licogliflozin may represent a promising novel treatment option for PCOS.

Interacting Quantum Atoms Method for Crystalline Solids.

An implementation of the Interacting Quantum Atoms method for crystals is presented. It provides a real space energy decomposition of the energy of crystals in which all energy components are physically meaningful. The new package ChemInt enables one to compute intra-atomic and inter-atomic energies, as well as electron population measures used for quantitative description of chemical bonds in crystals. The implementation is tested and applied to characteristic molecular and crystalline systems with different types of bonding.

Beam-size effects on the measurement of sub-picosecond intrinsic laser induced damage threshold of dielectric oxide coatings.

Laser-induced damage experiments on HfO2 and Nb2O5 thin films were performed with 500 fs pulse duration at 1030 nm wavelength. Threshold fluences as a function of beam size have been determined for effective beam diameters ranging from 40 to 220 µm, in a single shot regime. The results suggest no beam-size effect related to material properties in the investigated range, but size effects related to the metrology. The results indicate the importance of appropriate focusing conditions and beam measurement to qualify the optics for use in lasers with large beam sizes.

"Excess" electrons in LuGe.

The monogermanide LuGe is obtained via high-pressure high-temperature synthesis (5-15 GPa, 1023-1423 K). The crystal structure is solved from single-crystal X-ray diffraction data (structure type FeB, space group Pnma, a=7.660(2) Å, b=3.875(1) Å, and c=5.715(2) Å, RF =0.036 for 206 symmetry independent reflections). The analysis of chemical bonding applying quantum-chemical techniques in position space was performed. It revealed-beside the expected 2c-Ge-Ge bonds in the germanium polyanion-rather unexpected four-atomic bonds between lutetium atoms indicating the formation of a polycation by the excess electrons in the system Lu3+ (2b)Ge2- ×1 e- . Despite the reduced VEC of 3.5, lutetium monogermanide is following the extended 8-N rule with the trend to form lutetium-lutetium bonds utilizing the electrons left after satisfying the bonding needs in the anionic Ge-Ge zigzag chain.

Tricyanidoferrates(-IV) and Ruthenates(-IV) with Non-Innocent Cyanido Ligands.

Exceptionally electron-rich, nearly trigonal-planar tricyanidometalate anions [Fe(CN)3 ]7- and [Ru(CN)3 ]7- were stabilized in LiSr3 [Fe(CN)3 ] and AE3.5 [M(CN)3 ] (AE=Sr, Ba; M=Fe, Ru). They are the first examples of group 8 elements with the oxidation state of -IV. Microcrystalline powders were obtained by a solid-state route, single crystals from alkali metal flux. While LiSr3 [Fe(CN)3 ] crystallizes in P63 /m, the polar space group P63 with three-fold cell volume for AE3.5 [M(CN)3 ] is confirmed by second harmonic generation. X-ray diffraction, IR and Raman spectroscopy reveal longer C-N distances (124-128 pm) and much lower stretching frequencies (1484-1634 cm-1 ) than in classical cyanidometalates. Weak C-N bonds in combination with strong M-C π-bonding is a scheme also known for carbonylmetalates. Instead of the formal notation [Fe-IV (CN- )3 ]7- , quantum chemical calculations reveal non-innocent intermediate-valent CN1.67- ligands and a closed-shell d10 configuration for Fe, that is, Fe2- .

Ianalumab (VAY736) in primary Sjögren's syndrome: assessing disease activity using multi-modal ultrasound.

OBJECTIVES: To apply serial ultrasound (US) assessments to show effects of ianalumab (anti-BAFF-R monoclonal antibody) on inflamed salivary glands of patients with primary Sjögren's syndrome (pSS). METHODS: In a single-centre, 24-week double-blind study (NCT02149420), 27 pSS patients of moderate-to-severe activity were randomly assigned to receive a single i.v. dose of either 3 mg/kg or 10 mg/kg ianalumab, or placebo. Concurrent with clinical and laboratory outcomes, multi-modal US images were acquired of bilateral parotid glands (PG) and submandibular glands (SMG) at weeks 0, 6, 12, and 24. Applied US modalities included 1) B-mode echostructure scored by de Vita classification, 2) macrovascular blood flow by power Doppler, and in PG only 3) microvascularisation using contrast-enhanced US (area under the curve, time to peak or TTP) and 4) gland stiffness by sonoelastography. RESULTS: Clinical study results were previously published. US data for PG differed from SMG but were comparable between respective left and right sides of these glands. Numerical improvements in salivary gland quality and declining tissue inflammation were observed in treated versus placebo groups, including more patients achieving ≥1-point reduction from baseline in De Vita score, together with trends towards decreased perfusion and stiffness. Correlations between clinical endpoints and US parameters were largely restricted to microvascular perfusion TTP and at the 12-week timepoint when ianalumab effects were predicted at maximal. CONCLUSIONS: Early in vivo signs of salivary gland improvement in response to an effective intervention can be shown without need of biopsy by using a non-invasive, comprehensive, ultrasound-based approach over multiple time points.

Treatment of primary Sjögren's syndrome with ianalumab (VAY736) targeting B cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity.

OBJECTIVES: To evaluate the efficacy and safety of ianalumab (VAY736), a B cell-depleting, B cell activating factor receptor-blocking, monoclonal antibody, in patients with active primary Sjögren's syndrome (pSS) in a double-blind, placebo-controlled, phase II, single-centre study. METHODS: Patients with pSS, EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) ≥6, were randomised to ianalumab single infusion at either 3 mg/kg (n=6), 10 mg/kg (n=12) or placebo (n=9). Outcomes were measured blinded at baseline and weeks 6, 12, 24, and unblinded at end of study (EoS) when B cell numbers had recovered. Clinical outcomes included ESSDAI, EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), salivary flow rate, ocular staining score, physician global assessment and patient assessments of fatigue and general quality of life. Laboratory-based measures included circulating leucocyte subsets and markers of B cell activity. RESULTS: A similar trend showing positive therapeutic effect by ianalumab was observed across the primary clinical outcome (ESSDAI) and all secondary clinical outcomes (ESSPRI, Multidimensional Fatigue Inventory, Short Form-36, global assessments by physician and patient) versus the placebo-treated group. Rapid and profound B cell depletion of long-lasting duration occurred after a single infusion of ianalumab at either dose. Serum Ig light chains decreased, with return to baseline levels at EoS. Changes in some clinical outcomes persisted through to EoS in the higher dose group. Adverse effects were largely limited to mild to moderate infusion reactions within 24 hours of ianalumab administration. CONCLUSIONS: Overall results in this single-dose study suggest potent and sustained B cell depletion by ianalumab could provide therapeutic benefits in patients with pSS without major side effects.

Polar-Covalent Bonding Beyond the Zintl Picture in Intermetallic Rare-Earth Germanides.

A comparative chemical bonding analysis for the germanides La2 MGe6 (M=Li, Mg, Al, Zn, Cu, Ag, Pd) and Y2 PdGe6 is presented, together with the crystal structure determination for M=Li, Mg, Cu, Ag. The studied compounds adopt the two closely related structure types oS72-Ce2 (Ga0.1 Ge0.9 )7 and mS36-La2 AlGe6 , containing zigzag chains and corrugated layers of Ge atoms bridged by M species, with La/Y atoms located in the biggest cavities. Chemical bonding was studied by means of the quantum chemical position-space techniques QTAIM (quantum theory of atoms in molecules), ELI-D (electron localizability indicator), and their basin intersections. The new penultimate shell correction (PSC0) method was introduced to adapt the ELI-D valence electron count to that expected from the periodic table of the elements. It plays a decisive role to balance the Ge-La polar-covalent interactions against the Ge-M ones. In spite of covalently bonded Ge partial structures formally obeying the Zintl electron count for M=Mg2+ , Zn2+ , all the compounds reveal noticeable deviations from the conceptual 8-N picture due to significant polar-covalent interactions of Ge with La and M ≠ Li, Mg atoms. For M=Li, Mg a formulation as a germanolanthanate M[La2 Ge6 ] is appropriate. Moreover, the relative Laplacian of ELI-D was discovered to reveal a chemically useful fine structure of the ELI-D distribution being related to polyatomic bonding features. With the aid of this new tool, a consistent picture of La/Y-M interactions for the title compounds was extracted.

A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo-controlled first-in-human and first-in-patient trials.

AIMS: To evaluate the safety, pharmacokinetics and pharmacodynamics of SAR425899, a novel polypeptide, active as an agonist at both the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCR), in healthy volunteers and in overweight/obese patients with type 2 diabetes (T2D). METHODS: Subcutaneous administrations of SAR425899 were tested in two randomized, placebo-controlled, double-blind clinical trials. In the first trial, healthy overweight volunteers (body mass index [BMI] 25-30 kg/m2 ; n = 32) received single-ascending doses (0.01-0.1 mg) of SAR425899 or placebo. In the second, a multiple-ascending-dose trial (NCT02411825), healthy normal- to overweight volunteers (BMI 20-30 kg/m2 ; n = 40) and overweight/obese patients with T2D (BMI 28-42 kg/m2 ; n = 36) received daily doses of SAR425899 or placebo over 21 or 28 days, respectively. RESULTS: The most frequently reported adverse events were gastrointestinal; gastrointestinal side effects were less pronounced in patients with T2D compared with healthy volunteers. SAR425899 significantly reduced levels of fasting plasma glucose (P < 0.05 vs. placebo) and glycated haemoglobin (P < 0.001 versus placebo) in patients with T2D. Additionally, SAR425899 led to reductions in body weight, with a maximal reduction of 5.32 kg in healthy volunteers and 5.46 kg in patients with T2D (P < 0.001 vs. placebo) at end of treatment. CONCLUSIONS: SAR425899 was well tolerated and led to favourable glycaemic effects in patients with T2D and weight reduction in both healthy volunteers and patients. Whether dual GLP-1R/GCR agonism represents a treatment method that is superior to pure GLP-1R agonists for obesity and diabetes treatment remains to be confirmed.

On Fe-Fe Dumbbells in the Ideal and Real Structures of FeGa3.

The intermetallic phase FeGa3 belongs to the rare examples of substances with transition metals where semiconducting behavior is found. The necessary electron count of 17 ve/fu can be formally derived from eight Fe-Ga and one Fe-Fe two-center-two-electron bond. The situation is reminiscent of the well-known Fe2(CO)9 scenario, where a direct Fe-Fe two-center-two-electron bond was shown to not be present. Fe-Fe interaction in FeGa3 and its substitution variants represents the crucial point for explanation of electronic, thermal transport, and optical properties of this material. Chemical bonding analysis in position space of FeGa3 and Fe2(CO)9 on the basis of the topology of the electron localizability indicator distribution, QTAIM atoms, two- and three-center delocalization indices, domain natural orbitals, IQA analysis, and an evaluation of the Fe-Fe dissociation energy yields a complete picture of the partially compensated Fe-Fe bond, which is nevertheless strong enough to be of decisive importance. Structural reinvestigation of differently synthesized single crystals leads to the composition Fe1+ xGa3 (0 ≤ x ≤ 0.018), where the additional Fe atoms are predicted from DFT/PBE calculations to yield a magnetic moment of about 2 µB/Fe2 atom and metallic in-gap states. Accompanying magnetization and ESR measurements are consistent with this picture.

Safety, pharmacokinetics and pharmacodynamics of single rising doses of BI 655064, an antagonistic anti-CD40 antibody in healthy subjects: a potential novel treatment for autoimmune diseases.

PURPOSE: The CD40-CD40L pathway is a promising treatment target for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and lupus nephritis. The safety, pharmacokinetics and pharmacodynamics of BI 655064, a novel humanised antagonistic anti-CD40 monoclonal antibody, were investigated in this first-in-human trial. METHODS: Healthy male subjects (n = 72) were randomised 3:1, within each BI 655064 dose group, to single intravenous (IV; 0.2-120 mg) or subcutaneous (SC; 40-120 mg) doses of BI 655064 or placebo. Safety, plasma exposure, CD40 receptor occupancy and CD40L-induced CD54 upregulation were assessed over 12 weeks. RESULTS: Adverse events (AEs) were reported in 43% of subjects (n = 31). Frequency and intensity of AEs were generally similar between BI 655064 and placebo and showed no dose relationship. The most frequent AEs were headache and nasopharyngitis. One mild rash and one local reaction occurred with SC BI 655064; two serious AEs were reported, both judged unrelated to BI 655064. Pharmacokinetic evaluation demonstrated a more than proportional increase in plasma exposure relative to BI 655064 dose, with a terminal half-life between 4 h and 4 days IV and approximately 5 days SC; doses ≥ 20 mg IV and 120 mg SC showed > 90% CD40 receptor occupancy and inhibition of CD54 upregulation, which lasted 7 days in the 120 mg IV and SC groups. CONCLUSIONS: Single doses up to 120 mg BI 655064 IV and SC were well tolerated and showed a high potential to block the CD40-CD40L pathway, supporting further clinical development of BI 655064 in patients with autoimmune disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01510782.

DEVELOPMENT OF THE ONTARIO DECISION FRAMEWORK: A VALUES BASED FRAMEWORK FOR HEALTH TECHNOLOGY ASSESSMENT.

OBJECTIVES: In 2007, the Ontario Health Technology Advisory Committee (OHTAC) developed a decision framework to guide decision making around nondrug health technologies. In 2012, OHTAC commissioned a revision of this framework to enhance its usability and deepen its conceptual and theoretical foundations. METHODS: The committee overseeing this work used several methods: (a) a priori consensus on guiding principles, (b) a scoping review of decision attributes and processes used globally in health technology assessment (HTA), (c) presentations by methods experts and members of review committees, and (d) committee deliberations over a period of 3 years. RESULTS: The committee adopted a multi-criteria decision-making approach, but rejected the formal use of multi-criteria decision analysis. Three broad categories of attributes were identified: (I) context criteria attributes included factors such as stakeholders, adoption pressures from neighboring jurisdictions, and potential conflicts of interest; (II) primary appraisal criteria attributes included (i) benefits and harms, (ii) economics, and (iii) patient-centered care; (III) feasibility criteria attributes included budget impact and organizational feasibility. CONCLUSION: The revised Ontario Decision Framework is similar in some respects to frameworks used in HTA worldwide. Its distinctive characteristics are that: it is based on an explicit set of social values; HTA paradigms (evidence based medicine, economics, and bioethics/social science) are used to aggregate decision attributes; and that it is rooted in a theoretical framework of optimal decision making, rather than one related to broad social goals, such as health or welfare maximization.

The effect of sacubitril/valsartan compared to olmesartan on cardiovascular remodelling in subjects with essential hypertension: the results of a randomized, double-blind, active-controlled study.

AIMS: Progressive aortic stiffening eventually leads to left ventricular (LV) hypertrophy and heart failure if left untreated. Anti-hypertensive agents have been shown to reverse this to some extent. The effects of sacubitril/valsartan (LCZ696), a dual-action angiotensin receptor blocker (ARB), and neprilysin inhibitor, on arterial stiffness and LV remodelling have not been investigated. METHODS AND RESULTS: This was a randomized, multi-centre, double-blind, double-dummy, active-controlled, parallel group, study to compare the effects on cardiovascular remodelling of sacubitril/valsartan with those of olmesartan in patients with hypertension and elevated pulse pressure. Magnetic resonance imaging scans were used to assess LV mass and local aortic distensibility, at baseline and at 12 and 52 weeks after initiation of treatment. Central pulse and systolic pressure were determined using a SphymoCor® XCEL device at each time point. A total of 114 patients were included, with 57 in each treatment group. The mean age was 59.8 years, and 67.5% were male. Demographic characteristics did not vary between the two sets of patients. Left ventricular mass index decreased to a greater extent in the sacubitril/valsartan group compared to the olmesartan group from baseline to 12 weeks (-6.36 vs. -2.32 g/m2; P = 0.039) and from baseline to 52 weeks (-6.83 vs. -3.55 g/m2; P = 0.029). These differences remained significant after adjustment for systolic blood pressure (SBP) at follow-up (P = 0.036 and 0.019 at 12 and 52 weeks, respectively) and similar signals (though formally non-significant) were observed after adjusting for changes in SBP (P = 0.0612 and P = 0.0529, respectively). There were no significant differences in local distensibility changes from baseline to 12 or 52 weeks between the two groups; however, there was a larger reduction in central pulse pressure for the sacubitril/valsartan group compared to the olmesartan group (P = 0.010). CONCLUSION: Since LV mass change correlates with cardiovascular prognosis, the greater reductions in LV mass indicate valuable advantages of sacubitril/valsartan compared to olmesartan. The finding that LV mass index decrease might be to some extent independent of SBP suggests that the effect of the dual-acting agent may go beyond those due to its BP-lowering ability.

Beliefs Regarding Asthma Management Relating to Asthma Action Plans (AAPs) of African American Caregivers Residing in Newark, New Jersey Public Housing Communities.

PURPOSE: The purpose of this study was to explore the beliefs regarding asthma management and Asthma Action Plans (AAPs) of African American caregivers residing in three New Jersey public housing communities in Newark, New Jersey. DESIGN: A qualitative methods design was accomplished using semi-structured interviews with a purposive sample of nine African American caregivers of children with asthma. Information was coded using N'VIVO™; the textual analysis combined codes into categories, which were then assembled into themes. RESULTS: Self-determination was found to be a fundamental goal of asthma management; however, three themes emerged as barriers and facilitators to this goal: challenges in the urban environment, preference of familial methods, and access to medical care. CONCLUSIONS: Findings from this study regarding minority caregivers' beliefs regarding difficulty navigating the health care system coupled with insurance instability, leading to use of Emergency Departments, are consistent with past research. Although caregivers expressed belief in use of prescribed medications as indicated on AAPs, familial methods, found to provide a sense of control over asthma, were preferred.

Chemical Bonding Analysis as a Guide for the Preparation of New Compounds: The Case of VIrGe and HfPtGe.

The chemical bonding of transition metal compounds with a MgAgAs-type of crystal structure is analyzed with quantum chemical position-space techniques. The observed trends in QTAIM Madelung energy and nearest neighbor electron sharing explain the occurrence of recently synthesized MgAgAs-type compounds, TiPtGe and TaIrGe, at the boundary to the TiNiSi-type crystal structure. These bonding indicators are used to identify favorable element combinations for new MgAgAs-type compounds. The new phases-the high-temperature VIrGe and the low-temperature HfPtGe-showing this type of crystal structure are prepared and characterized by powder X-ray diffraction and differential thermal analysis.

PUBLIC AND PATIENT INVOLVEMENT IN HEALTH TECHNOLOGY ASSESSMENT: A FRAMEWORK FOR ACTION.

OBJECTIVE: As health technology assessment (HTA) organizations in Canada and around the world seek to involve the public and patients in their activities, frameworks to guide decisions about whom to involve, through which mechanisms, and at what stages of the HTA process have been lacking. The aim of this study was to describe the development and outputs of a comprehensive framework for involving the public and patients in a government agency's HTA process. METHODS: The framework was informed by a synthesis of international practice and published literature, a dialogue with local, national and international stakeholders, and the deliberations of a government agency's public engagement subcommittee in Ontario, Canada. RESULTS: The practice and literature synthesis failed to identify a single, optimal approach to involving the public and patients in HTA. Choice of methods should be considered in the context of each HTA stage, goals for incorporating societal and/or patient perspectives into the process, and relevant societal and/or patient values at stake. The resulting framework is structured around four actionable elements: (i) guiding principles and goals for public and patient involvement (PPI) in HTA, (ii) the establishment of a common language to support PPI efforts, (iii) a flexible array of PPI approaches, and (iv) on-going evaluation of PPI to inform adjustments over time. CONCLUSIONS: A public and patient involvement framework has been developed for implementation in a government agency's HTA process. Core elements of this framework may apply to other organizations responsible for HTA and health system quality improvement.