Part 1A Research Articles

SEC issues proposed investment adviser reporting and disclosure rules

Purpose – To explain proposed rules and amendments recently issued by the USA Securities and Exchange Commission (SEC) that would impose more detailed reporting requirements for investment advisers that file Form ADV. A companion article describes the SEC’s proposed registered investment company reporting rules which were issued simultaneously. Design/methodology/approach – Describes the SEC’s reasoning for collecting more detailed data, introduces the proposed separate account reporting requirements for SEC-registered investment advisers, explains proposed amendments to Part 1A of Form ADV, describes a proposed codification of SEC staff positions that provide for so-called “umbrella registrations” by closely related advisory firms, and details two proposed amendments to Advisers Act Rule 204-2, the books and records rule, which would require investment advisers to maintain additional materials related to the calculation and distribution of performance information. Findings – Many questions still remain as to how the final rules will eventually take shape; however, it is evident that investment advisers will be subject to a wider array of reporting requirements. Investment advisors are likely to incur increased costs as a result of the proposed rules and amendments, and production of the reports could necessitate a revamp of their various internal procedures. Also, access to additional and enhanced information will have consequences for investment companies with respect to SEC examinations and enforcement activity. Practical implications – Investment advisers should understand that detailed new regulatory reporting is coming and, more specifically, separately managed account clients of investment advisers should be made aware of the proposed reporting requirements. Originality/value – Practical guidance from experienced investment funds lawyer.

Learning to become a nurse prescriber in New Zealand using a constructivist approach: A narrative case study.

IntroductionMedical prescribing, in terms of both education and practice, has been extensively researched but this has not been the case with nurse prescribing (Coombes, Mitchell, & Stowasser, 2008; Franson, Dubois, de Kam, Burggraaf, & Cohen, 2009; Garbutt et al., 2006; Gwee, 2009). One reason for this is that internationally, prescriptive authority differs between countries, and hence the educational preparation for nurses to prescribe also varies. This has detracted from consistent research into the educational preparation and practice of nurse prescribing despite the fact that registered nurse prescribing is well established in some countries, notably the United Kingdom and is generally regarded positively (Latter et al., 2010).This article describes the pedagogical underpinnings of one of the first postgraduate programmes developed for nurse practitioners to gain prescriptive authority. Nurses intending to become nurse practitioner prescribers were interviewed to gain an understanding of their experiences of undertaking these postgraduate prescribing programmes.BackgroundNurse prescribing in New Zealand: A brief historyIn New Zealand, the nurse practitioner role was introLim, duced to improve patient access to health care services (National Health Committee, 2000). The introduction of the nurse practitioner role also represented a significant advance for professional nursing and positioned nurses to practice autonomously. Autonomous practice for nurse practitioners includes performing comprehensive health assessments, clinical diagnosis and prescribing treatments. The introduction of nurse prescribing in New Zealand has developed concurrently with the role of the nurse practitioner (Nursing Council of New Zealand, 2005). Since 1999, nurse practitioners in New Zealand can prescribe as long as they have completed the necessary educational preparation (Lim, Honey, & Kilpatrick, 2007).Prescriptive authority in New Zealand is outlined in the Medicines Act of 1981 and in the Medicines Regulation of 1984. Under the Act, health professionals with prescriptive authority (authorised prescribers) can prescribe all medicines from Part 1A or Part 1B of the Schedule 1 of the Medicines Regulations. Three health professional groups were authorised prescribers (doctors, dentists and midwives) until 1999 (Medicines Amendment Act 1999) when prescriptive authority for nurses was considered by the New Zealand government and the legislation was amended.Educational preparation for prescribing was included in the undergraduate programme for doctors, dentists and midwives, which was not the case for nurses. Therefore the term, designated prescribers, was added in the amendments to the Act. Unlike authorised prescribers, designated prescribers are required to undergo additional education in pharmacology and therapeutics to become prescribers. Since 1999, further amendments to the Act (in 2011) extended prescriptive authority to pharmacists and diabetes nurse specialists, so that pharmacists, diabetes nurse specialists and nurse practitioners could become designated prescribers. The extension was further refined in 2013 (Medicines Amendment Act 2013), when nurse practitioner prescribers gained the same prescriptive authority as doctors, dentists and midwives as authorised prescribers, and a new category of prescribers called delegated prescribers was added to the Act. There are now three levels of prescriptive authority in New Zealand: authorised, designated and delegated. These legislative changes bring challenges and potential for confusion to nurse prescribing roles.Educational preparation of nurses for prescribing has always been considered in the changes to the legislation. Educational preparation includes knowledge of applied biological sciences, advanced assessment and diagnoses, pharmacology and therapeutics, alongside a prescribing practicum where the knowledge is applied within a clinical context. …

MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease

Objective: To determine if the non-motor sections of the Movement Disorder Society's (MDS) version of the Unified Parkinson's Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinson's disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). Methods: Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. Results: One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. Conclusions: This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD.

Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial.

Patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are at high risk for liver disease progression. However, interferon-based treatments for HCV infection have significant toxicities, limiting treatment uptake. To assess the all-oral 3 direct-acting antiviral (3D) regimen of ombitasvir, paritaprevir (co-dosed with ritonavir [paritaprevir/r]), dasabuvir, and ribavirin in HCV genotype 1-infected adults with HIV-1 co-infection, including patients with cirrhosis. TURQUOISE-I is a randomized, open-label study. Part 1a of this pilot study was conducted at 17 sites in the United States and Puerto Rico between September 2013 and August 2014 and included 63 patients with HCV genotype 1 and HIV-1 co-infection who were HCV treatment-naive or had history of prior treatment failure with peginterferon plus ribavirin therapy. The study allowed enrollment of patients, including those with cirrhosis, with a CD4+ count of 200/mm3 or greater or CD4+ percentage of 14% or more and plasma HIV-1 RNA suppressed while taking a stable atazanavir- or raltegravir-inclusive antiretroviral regimen. Ombitasvir/paritaprevir/r, dasabuvir, and ribavirin for 12 or 24 weeks of treatment as randomized. The primary assessment was the proportion of patients with sustained virologic response (HCV RNA <25 IU/mL) at posttreatment week 12 (SVR12). Among patients receiving 12 or 24 weeks of 3D and ribavirin, SVR12 was achieved by 29 of 31 (94%; 95% CI, 79%-98%) and 29 of 32 patients (91%; 95% CI, 76%-97%), respectively. Of the 5 patients who did not achieve SVR, 1 withdrew consent, 2 had confirmed virologic relapse or breakthrough, and 2 patients had clinical history and phylogenetic evidence consistent with HCV reinfection. The most common treatment-emergent adverse events were fatigue (48%), insomnia (19%), nausea (18%), and headache (16%). Adverse events were generally mild, with none reported as serious or leading to discontinuation. No patient had a confirmed HIV-1 breakthrough of 200 copies/mL or greater during treatment. In this open-label, randomized uncontrolled study, treatment with the all-oral, interferon-free 3D-plus-ribavirin regimen resulted in high SVR rates among patients co-infected with HCV genotype 1 and HIV-1 whether treated for 12 or 24 weeks. Further phase 3 studies of this regimen are warranted in patients with co-infection. clinicaltrials.gov Identifier: NCT01939197.

An evaluation of demographic factors affecting performance in a paediatric membership multiple-choice examination

ObjectiveTo determine if demographic factors are associated with outcome in a multiple-choice, electronically marked paediatric postgraduate examination.MethodRetrospective analysis of pass rates of UK trainees sitting Membership of the Royal College...

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497P - Dose-Escalation Phase I Study of Cabazitaxel (CBZ) + Gemcitabine (GEM) in Patients (PTS) with Metastatic or Unresectable Advanced Solid Malignancy

ABSTRACT Rationale Gem + taxane combinations have shown activity in some advanced cancers. Cbz (a novel taxane) + prednisone (P) improved overall survival vs mitoxantrone + P in pts with metastatic castration-resistant prostate cancer previously treated with docetaxel (de Bono 2010). Methods A Phase I study (NCT01001221) was conducted to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of Cbz + Gem (parts 1a and 1b) and to evaluate antitumour activity at the MTD (part 2). Pts with histologically or cytologically confirmed metastatic or unresectable solid tumours without existing standard treatment were eligible. Cohorts of 3–6 pts were treated with Cbz (15–20 mg/m2 1-h infusion) followed by Gem (700–1000 mg/m2) on d1 and Gem alone on d8 (part 1a). The administration sequence on d1 was then reversed (part 1b), based on preliminary PK data. Results Of the 12 pts in part 1a, 5 pts were treated at Cbz 20 mg/m2 + Gem 1000 mg/m2 dose level (DL 20/1000), 5 pts at DL 15/900 and 2 pts at DL 15/700. In part 1b, all 6 pts were treated at the lowest DL (700/15) allowed. At all DLs, ≥ 2 pts experienced a DLT, regardless of administration sequence. DLTs were febrile neutropenia (FN) (4 pts), Grade (Gr) 4 neutropenia (2 pts), Gr 4 thrombocytopenia (2 pts) and Gr 3 AST increase (1 pt). No MTD was established and part 2 was not performed. All pts experienced at least 1 treatment-emergent AE (TEAE); the most frequent all grade non-haematological TEAEs were fatigue 66.7%, decreased appetite 50.0%, diarrhoea 44.4%, nausea 38.9% and weight decrease 33.3%. Gr 3–4 haematological toxicities included neutropenia 66.7%, thrombocytopenia 33.3% and FN 22.2%. Nine pts continued study treatment and received 6–22 cycles; 3 pts had a partial response (melanoma, prostate small cell and appendiceal tumours), while 8 pts experienced stable disease. PK analysis did not reveal a drug–drug interaction between Cbz and Gem. Conclusion The MTD of Cbz + Gem could not be established due to DLTs. Antitumour activity was observed and drug administration sequence did not affect the toxicity profile. Further investigation of alternative dosing regimens is warranted in an effort to establish a tolerable combination. Disclosure P.M. LoRusso: Has received research funding from Sanofi. J. Yin: Is a Sanofi employee and owns Sanofi stocks and shares. S. Doroumian: Is a Sanofi employee (pharmacokineticist) and owns Sanofi stocks and shares. X. Zhi: Is a Sanofi employee (statistician) and owns Sanofi stocks and shares. A.J. Olszanski: Research funding - Sanofi supplies support for the conduct of the study. All other authors have declared no conflicts of interest.

Formal Metatheory of Programming Languages in the Matita Interactive Theorem Prover

This paper is a report about the use of Matita, an interactive theorem prover under development at the University of Bologna, for the solution of the POPLmark Challenge, part 1a. We provide three different formalizations, including two direct solutions using pure de Bruijn and locally nameless encodings of bound variables, and a formalization using named variables, obtained by means of a sound translation to the locally nameless encoding. According to this experience, we also discuss some of the proof principles used in our solutions, which have led to the development of a generalized inversion tactic for Matita.

Analysis of Coconut Carbon Fibers for Gas Diffusion Layer Material

The main compound of natural fibers is a hydrocarbon. The heating of hydrocarbon in inert gas produces charcoal or carbon. Carbon materials are widely used for several purposes depending on the physical and electric properties, for example for hydrogen storage, conductive or reinforced plastics, catalyst supports, batteries and fuel cells. The main raw material of Gas diffusion Layer (GDL) of the Proton Exchange Membrane Fuel Cell (PEMFC) is a carbon. The properties of GDL are porous and electron-conductive material, because of the function of GDL is to distribute the gas as fuel and electricity conductors. This study aims to analyze the carbon fibers made from coconut fibers for the application of GDL materials. The carbon fiber was made using pyrolysis process in the inert gas (nitrogen) at a certain temperature according to the analysis of Differential Thermal Analysis (DTA) 3000C, 4000C, 5000C, 6000C, and 9000C. The crystalstructure, carbon content, powder density and morphology of carbon fibers were observed using X-Ray Diffraction (XRD), fixed carbon according to ASTM D 1762-64, Archimedes method (BS 19202 Part 1A), and Scanning Electron Microscope (SEM), respectively. The results showed that the structure of carbon was amorphous, and content of 51% ̶ 71%, powder density of 0.42g/cm3 ̶ 0.71g/cm3. The morphology having many parallel hollows like a tube that are close to each other with diameters of 2m ̶ 10m, and in the wall of tube there are some porous with sizes around 1m. According to this analysis, the coconut carbon fiber enables to be applied as candidate for a basic material of GDL.

W1038 Acute Upper Gastrointestinal Bleeding – Why Do Patients Die?

Introduction Despite advances in endoscopic haemostasis and pharmacological therapy, the mortality of Acute Upper Gastrointestinal Bleeding (AUGIB) in the UK remains high at 10%, increasing up to 26% for in-patient bleeds.1 Although achieving successful haemostasis is a key treatment goal, focusing management on prevention of secondary complications and comorbid illnesses may serve to reduce the mortality burden of the disease. We aimed to determine the specific cause of death in a large prospective UK audit of patients presenting with AUGIB. Methods Analysis was performed on 6750 patients included in the 2007 UK Comparative Audit of Upper Gastrointestinal Bleeding and the Use of Blood.1 In this study prospective data were collected electronically on consecutive patients presenting to 208 UK hospitals with AUGIB between 1 May and 30 June 2007. In all patients whom died, clinicians were asked to comment whether they thought the death was due to haemorrhage or a related cause. In a separate question, they were then asked to list the mode of death, as listed as “Part 1A” on the patient9s death certificate. Results Of 6750 patients included in the final analysis, 675 (10%) died. Of the 675 patients who died, in 227 (33.6%) the clinician thought death was a direct result of gastrointestinal bleeding and in 448 (66.4%) it was from another cause. In terms of the mode of death as listed as “Part 1A” on the patient9s death certificate, complete information was available for 474/675 (70.2%) patients. The majority of deaths (74%, 351/474) were non-bleeding related. The most common modes of death reported were respiratory failure, terminal malignancy, septicaemia and cardiac failure. The majority of patients who died from haemorrhage were acute admissions (66%, 81/123). There was no significant difference in the mean age of those who died as a direct result of bleeding, compared with those who died from another cause (73.8±15.9 vs 75.8±14.9). Similarly there was no significant difference in use of NSAIDS in those who died of a bleeding (7.5%) vs non-bleeding cause (6.5%). Conclusion The majority of patients admitted with AUGIB did not die from further bleeding, but rather from another cause. Improving the outcome of AUGIB will require optimisation of treatment to reduce the risk of cardio-respiratory complications, sepsis and multi-organ failure rather than focusing only on achieving successful endoscopic haemostasis.

PTH-020 Acute upper gastrointestinal bleeding: why do patients die?

<h3>Introduction</h3> Despite advances in endoscopic haemostasis and pharmacological therapy, the mortality of Acute Upper Gastrointestinal Bleeding (AUGIB) in the UK remains high at 10%, increasing up to 26% for in-patient bleeds.1 Although achieving successful haemostasis is a key treatment goal, focusing management on prevention of secondary complications and comorbid illnesses may serve to reduce the mortality burden of the disease. We aimed to determine the specific cause of death in a large prospective UK audit of patients presenting with AUGIB. <h3>Methods</h3> Analysis was performed on 6750 patients included in the 2007 UK Comparative Audit of Upper Gastrointestinal Bleeding and the Use of Blood.1 In this study prospective data were collected electronically on consecutive patients presenting to 208 UK hospitals with AUGIB between 1 May and 30 June 2007. In all patients whom died, clinicians were asked to comment whether they thought the death was due to haemorrhage or a related cause. In a separate question, they were then asked to list the mode of death, as listed as “Part 1A” on the patient9s death certificate. <h3>Results</h3> Of 6750 patients included in the final analysis, 675 (10%) died. Of the 675 patients who died, in 227 (33.6%) the clinician thought death was a direct result of gastrointestinal bleeding and in 448 (66.4%) it was from another cause. In terms of the mode of death as listed as “Part 1A” on the patient9s death certificate, complete information was available for 474/675 (70.2%) patients. The majority of deaths (74%, 351/474) were non-bleeding related. The most common modes of death reported were respiratory failure, terminal malignancy, septicaemia and cardiac failure. The majority of patients who died from haemorrhage were acute admissions (66%, 81/123). There was no significant difference in the mean age of those who died as a direct result of bleeding, compared with those who died from another cause (73.8±15.9 vs 75.8±14.9). Similarly there was no significant difference in use of NSAIDS in those who died of a bleeding (7.5%) vs non-bleeding cause (6.5%). <h3>Conclusion</h3> The majority of patients admitted with AUGIB did not die from further bleeding, but rather from another cause. Improving the outcome of AUGIB will require optimisation of treatment to reduce the risk of cardio-respiratory complications, sepsis and multi-organ failure rather than focusing only on achieving successful endoscopic haemostasis.

Diaphragm structure of light sound converter

A diaphragm (1) of a light sound converter having a high performance, suitable for mass-production, and having a slit (1s) formed therein, wherein a light emitting element and a light receiving element are disposed at a position opposed to a reflective part (1a) of the diaphragm (1) having a pressure receiving surface part (1d) and the reflective part (1a), and light is radiated from the light emitting element to the reflective part (1a) of the diaphragm (1) and the reflected light from the reflective part (1a) is received by the light receiving element, whereby the position of the diaphragm (1) can be detected.

The ‘natural’ endpoint of dementia: death from cachexia or dehydration following palliative care?

To investigate the causes of death in nursing home patients with dementia, and to compare causes of death in patients who survive until the final phase of dementia with those who die before reaching that phase, adjusted for potential confounders. Observational analysis of a cohort of patients with a prospective follow-up. Psychogeriatric nursing home 'Joachim en Anna' in Nijmegen, the Netherlands. Eight hundred and ninety dementia patients admitted between 1980 and 1989. All patients were followed until death. The final phase of dementia was defined as total impairment on 20 items of a functional status questionnaire. Immediate causes of death (part 1a of the Dutch death certificate) were classified by the International Classification of Health Problems in Primary Care. The three most important reported immediate causes of death were cachexia/dehydration (35.2%), cardio-vascular disorders (20.9%) and acute pulmonary diseases (20.1%), mainly pneumonia. Cachexia/dehydration was particularly common as a cause of death of patients who survived to the final phase (53.2%); survival to the final phase of dementia was an independent predictor of cachexia/dehydration as an immediate cause of death with reference to cardiovascular disorders in multinomial regression adjusted for age at death, gender, and type of dementia. Patients who survive to the final phase of dementia are more likely to die from cachexia or dehydration than those who die before. The findings contribute to a debate on what should be reported as the immediate cause of death in dementia including perspectives from a palliative care viewpoint.

Commentary on: Divide and conquer; a defence of functional localisers

We would like to thank Rebecca and her colleagues (Saxe et al., this issue) for providing a comprehensive and engaging commentary on our target article (Friston et al. this issue). We hope this exchange will clarify the different perspectives adopted by people who do and do not use fROI. However, this debate will not be resolved here: it will only be resolved by looking at the practice of imaging neuroscientists in the years to come. We suspect that fROI will have disappeared by then, because the questions they address are fundamentally limited. fROI are already being subverted by the growing interest in high-resolution functional imaging and multivariate characterisations of fine-scale distributed responses. The current issue is more pragmatic: it is becoming more difficult for cognitive neuroscientists to publish imaging papers that involve extra-striate or inferotemporal areas, without conforming to fROI dogma (see Appendix A). Our hope is to reverse this trend. Contentious issues sometimes arise from a misconception of the others position. It was useful to have the response of Saxe et al. because we realise now how proponents of fROI may miss the point of our critique. Our point was that, if one wishes to identify brain regions using functional criteria (i.e., a ‘‘localiser’’ contrast), then it is best to (1) embed the localiser within an explicit factorial design, in the same experimental session; (2) use the contrast to constrain the search for brain regions showing the effects of interest (i.e., orthogonal main effects or interactions), rather than to average data over all voxels identified by the localising contrast. Thus, while we can imagine readers nodding thoughtfully during the first part of Saxe et al. (part 1A) – in which the authors describe a well-known issue in cognitive neuroscience that structure–function mappings may differ across individuals – this is not the point of contention. This inter-subject variability raises questions about the validity of matching brains purely on the basis of structure (e.g., by ‘‘normalising’’ to a template) in group

Le Québec à l'heure de la réforme du droit des sociétés (compagnies) ou le législateur schizophrène

How can two parts (1 and 1A) of a same statute (Quebec Compagnies Act) be of a such a different spirit and at the same time complementary (part 1A needs part I to be complete and effective) and serve for years and years without the risk of severe distorsions and misleading solutions ?

Books Reviews

International Labour ReviewVolume 144, Issue 1 p. 115-134 Books Reviews First published: 22 September 2008 https://doi.org/10.1111/j.1564-913X.2005.tb00561.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Book reviewed in this article: La France et le temps de travail (1814–2004). Edited by Patrick FRIDENSON and Bénédicte REYNAUD. Les acteurs de l'histoire du droit du travail. Edited by Jean-Pierre LE CROM. Recent books: Droit du travail. Aspects juridiques et pratiques. By Marianne FAVRE MOREILLON. Le télétravail. Une vague silencieuse. By Laurent TASKIN and Patricia VENDRAMIN. Le travail au singulier. Le lien social à l'épreuve de l'individualisation. By Patricia VENDRAMIN. Limits to globalization: Welfare states and the world economy. By Elmar RIEGER and Stephan LIEBFRIED. Monopsony in motion: Imperfect competition in labor markets. By Alan MANNING. Pathways out of poverty: Private firms and economic mobility in developing countries. Edited by Gary S. FIELDS and Guy PFEFFERMANN. Relaciones de trabajo en el nuevo siglo. By Héctor LUCENA. Targeting development: Critical perspectives on the Millennium Development Goals. Edited by Richard BLACK and Howard WHITE. New ILO publications: Application of international labour standards, 2005: Report of the Committee of Experts on the Application of Conventions and Recommendations. International Labour Conference, 93rd Session, 2005, Report III (Part 1A). Hours of work: From fixed to flexible? International Labour Conference, 93rd Session, 2005, Report III (Part 1 B). Application of international labour standards, 2005: Information document on ratifications and standards-related activities. International Labour Conference, 93rd Session, 2005, Report III (Part 2). Automotive industry trends affecting component suppliers. Report for discussion at the Tripartite Meeting on Employment, Social Dialogue, Rights at Work and Industrial Relations in Transport Equipment Manufacturing. Sectoral Activities Programme. Cooperation in a changing environment — ILO activities 2001–2004 (Volume I). Managing transitions: Governance for decent work (Volume II). Seventh European Regional Meeting, Budapest, February 2005. Report of the Director-General of the ILO. New forms and meanings of work in an increasingly globalized world. By Ronald DORE. ILO Social Policy Lectures series. The employment relationship. International Labour Conference, 95th Session, 2006, Report V (1). Yearbook of Labour Statistics 2004 (63rd issue) and Sources and methods: Labour statistics (Vols. 1–10). October Inquiry results: Statistics on occupational wages and hours of work and on food prices. Volume144, Issue1March 2005Pages 115-134 RelatedInformation

Synthesis and Structures of Highly Conducting Charge-Transfer Salts of Selenium Containing TTM-TTP Derivatives

Abstract Selenium-substituted TTM-TTP (2,5-bis[4,5-bis(methylthio)-1,3-dithiol-2-ylidene]-1,3,4,6-tetrathiapentalene) derivatives (1a–1d), in which several 1,3-dithiole rings of the bis-fused TTF framework are replaced by 1,3-diselenole rings, have been prepared. In particular, we have accomplished the first selenium substitution of the inner TTP part (1a). The 1:1 composition iodine salt, (1a)I3, is an insulator constructed of the donor trimers. The 1:1 GaCl4 salt, (1a)GaCl4, has a uniform column isostructural to the sulfur analog, (TTM-TTP)FeBr1.8Cl2.2; it exhibits metallic conduction down to about 60 K, the lowest metal–insulator (M–I) transition temperature in 1:1 salts. The donors 1c and 1d give the iodine salts isostructural to the sulfur analog, (TTM-TTP)(I3)5/3. By the selenium substitution, the M–I transition of (1d)(I3)5/3 is entirely suppressed.

New convergent synthesis of 1alpha,25-dihydroxyvitamin D3 and its analogues by Suzuki-Miyaura coupling between A-ring and C,D-ring parts.

A new convergent method for the synthesis of 1alpha,25-dihydroxyvitamin D(3) and its analogues has been developed that involves efficient preparation of the A-ring part 1a, (Z)-(3S,5R)-1-bromomethylene-3,5-bis(tert-butyldimethylsilyloxy)-2-methylenecyclohexane, starting from epichlorohydrin (4) and its Suzuki-Miyaura coupling reaction with the C,D-ring part 12. Thus, (R)-4 was converted to (3S,5R)-5-(tert-butyldimethylsilyloxy)-8-(trimethylsilyl)-oct-1-en-7-yn-3-ol (3a) through a ten-step reaction sequence in 49% overall yield. Compound 3a thus obtained was treated with a Ti(O-i-Pr)(4)/2 i-PrMgCl reagent and then with NBS to afford (Z)-(1S,2S,5R)-2-bromomethyl-3-[bromo(trimethylsilyl)methylene]-5-(tert-butyldimethylsilyloxy)cyclohexanol (10a) in 51% yield, from which 1a was obtained in 87% yield by sequential treatment with TBSCl/imidazole, DBU, and Cs(2)CO(3). The resulting A-ring intermediate 1a was reacted with alkenylboronate 12 in the presence of a PdCl(2)(dppf) catalyst to furnish 1alpha,25-dihydroxyvitamin D(3) in 82% yield after protodesilylation. Similarly, all of the other three possible stereoisomers of A-ring parts 1b, 1c, and 1d were prepared, from which 1-epi-, 3-epi-, and 1,3-di-epi-1alpha,25-dihydroxyvitamin D(3) were synthesized by coupling with 12 in excellent yield, respectively. Starting from 1a and 1c, des-C,D-1alpha,25-dihydroxyvitamin D(3) analogues, retiferol 13 and its 3-epi derivative, were also prepared, respectively.

Summary WG2 Part 1a: using neutrinos to study partons in the nucleon and the nucleus at the neutrino factory

A neutrino deep-inelastic scattering experiment at a neutrino factory is described. The improvements possible in extracting parton distribution functions both within the nucleon and the nuclear environment are shown. The intriguing possibility of using (anti)neutrino scattering off a polarized target to determine the individual partonic spin contributions to the nucleon is discussed.

Drinking water contamination in Walkerton, Ontario: positive resolutions from a tragic event

In May 2000, Escherichia coli O157:H7 and Campylobacter jejuni contaminated the drinking water supply in Walkerton, Ontario. Seven people died and over 2,000 were ill as a result. The Ontario Provincial Government set up a judicial Inquiry into the circumstances surrounding the outbreak and also moved quickly to introduce a new Drinking Water Regulation that incorporated some significant requirements for drinking water providers. The Inquiry itself was in three parts: (a) part 1 related to the events that occurred in Walkerton and why the water contamination occurred; (b) part 1A related specifically to the role of the Provincial Government in the event; and (c) part 2 related to the future of drinking water safety in Ontario with potential to influence regulation on a wider basis. A number of other actions were taken after Walkerton. In August 2000, the Ontario Government, through the Regulatory body, the Ontario Ministry of the Environment (MOE) (a) re-issued and revised the Ontario Drinking Water Objectives (ODWO) as the Ontario Drinking Water Standards (ODWS) and (b) introduced new regulations governing drinking water in Ontario--the Ontario Drinking Water Protection Regulation. One of the key features of the Drinking Water Protection Regulation was the requirement to produce an independent Engineers' Report on all water systems. This paper provides a unique perspective on the Walkerton tragedy and its aftermath. The author was active in many aspects of the resulting activity (Chair of the Ontario Water Works Association's (a section of the AWWA) Special Committee involved in Part 2 of the Walkerton Inquiry; author of several of the Engineers' Reports mandated by Regulation; reviewer on behalf of the Regulator of Engineers' Reports submitted by others). The Engineers' Reports were of interest because (1) the drinking water providers (mostly municipalities) were mandated by regulation to complete the Reports by specific dates and are paying for the Reports, (2) the work had to be done by a registered professional engineer who is not an employee of the owner or the operator if a different entity and (3) the engineer had to sign a declaration that the Regulator could rely on the accuracy of the Report. In other words, the Municipality retained the Engineer and paid them to produce the Report--the Engineer essentially carried the liability while the Regulator had the final say in the acceptability of the Report, a sort of eternal triangle of responsibilities. The paper will outline how the drinking water profession in North America worked together to provide the Walkerton Inquiry with the benefit of its experience and knowledge of best practices to the benefit of consumers and the drinking water providers. It will also outline the procedures adopted to produce the independent Engineers' Reports and how the findings are being applied to further improve drinking water safety in Ontario, across Canada and in similar situations around the world.