Settlement outcomes in sexual harassment complaints

This article examines the dispute resolution process of conciliation through a detailed study of Australian workplace sexual harassment complaints. It links two data sets: settlement details of a census of conciliated complaints lodged under all federal, State, and Territory anti-discrimination laws in a six-month period; and interviews undertaken with 71 professionals who have extensive, first-hand experience of conciliation processes in anti-discrimination jurisdictions. The article provides a critique of the effectiveness of conciliation as a form of ADR within the individualised constraints of current anti-discrimination laws.

The development of an effective and efficient dispute resolution processes for strata scheme disputes in peninsular Malaysia

Dispute resolution in strata schemes in Peninsular Malaysia should focus on more than just "settlement." The quality of the outcome, its sustainability and its relevance in supporting the basic principles of a good neighbourhood and self-governance in a strata scheme are also fundamental. Based on the comprehensive law movement, this thesis develops a theoretical framework for strata scheme disputes within the parameters of therapeutic jurisprudence, preventive law, alternative dispute resolution (ADR) and problem-solving courts. The therapeutic orientation of this model offers approaches that promote positive communication between disputing parties, preserve neighbour relations and optimise people's psychological and emotional well-being.

MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells

We have previously reported that human breast carcinoma (HBC) cell lines expressing the mesenchymal intermediate filament protein vimentin (VIM+) are highly invasive in vitro, and highly metastatic in nude mice when compared to their VIM- counterparts. Since only VIM+ cell lines can be induced to activate matrix metalloproteinase-2 (MMP-2) upon stimulation with Concanavalin A (Con A), we have examined here membrane type 1 MMP (MT1-MMP), a cell surface activator of MMP-2. Northern analysis reveals baseline expression of MT1-MMP in five of the six VIM+ cell lines studied (MDA-MB-231, MDA-MB-435, BT-549, Hs578T, MCF-7(ADR)), each of which showed variable activation of exogenous MMP-2 after treatment with Con A. In contrast, the four VIM-, poorly invasive HBC cell lines studied (MCF-7, T47D, MDA-MB 468, ZR-75-1) lacked baseline MT1-MMP mRNA expression, and showed no induction of either MT1-MMP expression or MMP-2-activation with Con A. Such differential MT1-MMP expression was confirmed in vivo using in situ hybridization analysis of nude mouse tumor xenografts of representative cell lines. Western analysis of the MDA-MB-231 cells revealed baseline membrane expression of a 60 kDa species, which was strongly induced by Con A treatment along with a weaker band co-migrating with that from MT1-MMP-transfected COS-1 cells (63 kDa), presumably representing latent MT1-MMP. MT1-MMP immunofluorescence strongly decorated Con A-stimulated MDA-MB-231 cells in a manner consistent with membranous staining, but did not decorate the unstimulated MDA-MB-231 cells or MCF-7 cells under either condition. Collectively, the results suggest the constitutive production of active MT1-MMP which is unavailable for either MMP-2 activation or immuno-decoration until Con A treatment. Since VIM expression arises by virtue of the so-called epithelial to mesenchymal transition (EMT) in invasive embryonic epithelia, we propose that this represents a major metastasis mechanism in breast carcinomas. MT1-MMP on the surface of such 'fibroblastoid' carcinoma cells may mediate a paracrine loop for the utilization of stromally produced MMP-2, and contribute to the poorer survival associated with VIM+ breast carcinomas.

Association of MMP-2 activation potential with metastatic progression in human breast cancer cell lines independent of MMP-2 production

Background: Expression of matrix metalloproteinase-2 (MMP-2), the 72-kd type IV collagenase/gelatinase, by cancer cells has been implicated in metastasis through cancer cell invasion of basement membranes mediated by degradation of collagen IV. However, the abundance of this latent proenzyme in normal tissues and fluids suggests that MMP-2 proenzyme utilization is limited by its physiological activation rather than expression alone. We previously reported activation of this proenzyme by normal and malignant fibroblastoid cells cultured on collagen I (vitrogen) gels. Purpose: Our purposes in this study were 1) to determine whether MMP-2 activation is restricted to the more invasive human breast cancer cell lines and 2) to localize the activating mechanism. Methods: Zymography was used to monitor MMP-2 activation through detection of latent MMP-2 (72 kd) and mature species of smaller molecular weight (59 or 62 kd). Human breast cancer cell lines cultured on plastic, vitrogen, and other matrices were thus screened for MMP- 2 activation. Collagen I-cultured cells were exposed to cycloheximide, a protein synthesis inhibitor, or to protease inhibitors to determine the nature of the MMP-2-activating mechanism. Triton X-114 (TX-114) detergent extracts from cells cultured on collagen I or plastic were incubated with latent MMP-2 and analyzed by zymography to localize the MMP-2 activator. Results: MMP-2 activation was only induced by collagen I culture in the more aggressive, highly invasive estrogen receptor-negative, vimentin-positive human breast cancer cell lines (Hs578T, MDA-MB-436, BT549, MDA-MB-231, MDA- MB-435, MCF-7(ADR)) and was independent of MMP-2 production. MMP-2 activation was detected in cells cultured on collagen I gels but not in those cultured on gelatin gels, Matrigel, or thin layers of collagen I or IV, gelatin, or fibronectin. Collagen-induced activation was specific for the enzyme species MMP-2, since MMP-9, the 92-kd type IV collagenase/gelatinase, was not activatable under similar conditions. MMP-2 activation was inhibited by cycloheximide and was sensitive to a metalloproteinase inhibitor but not to aspartyl, serine, or cysteinyl protease inhibitors. MMP-2 activation was detected in the hydrophobic, plasma membrane-enriched, TX-114 extracts from invasive collagen I-cultured cells. Conclusion: Collagen I-induced MMP-2 activation is restricted to highly invasive estrogen receptor-negative, vimentin-positive human breast cancer cell lines, is independent of MMP-2 production, and is associated with metastatic potential. Our findings are consistent with plasma membrane localization of the activator. Implications: The MMP-2 activation mechanism may represent a new target for diagnosis, prognosis, and treatment of human breast cancer.

Teaching dispute resolution ethics in the law curriculum

Dispute resolution processes such as mediation are now central to contemporary legal practice. For this reason it is critical that the law curriculum includes instruction on mediation ethics, so that law graduates enter the profession equipped to deal with ethical dilemmas arising in this context. However, our recent content analysis of the unit outlines for professional responsibility subjects in Australian law schools indicates that this important area of legal ethics is often excluded from the curriculum. In most Australian law schools, dispute resolution subjects (where mediation ethics might also be considered) continue to be offered as stand-alone electives in the law degree. This means that many law students are graduating without the ethical knowledge and judgment-making skills needed in dispute resolution environments. This is contrary to the intentions of the Threshold Learning Outcomes for Law. This paper argues that the current paucity of mediation ethics instruction in the Australian law curriculum is problematic, given mediation’s relevance to contemporary legal practice. The paper discusses the importance of including mediation ethics in the law curriculum, and the importance of dispute resolution more broadly as a mandatory component of the law degree in Australia. It offers an outline of a possible mediation ethics module that could be included in professional responsibility subjects.

Spam – Spim – Spit. En marknadsrättslig undersökning av marknadsföring via nya kommunikationstekniker

I boken behandlas nya kommunikationstekniker och olika marknadsföringsmetoder som har uppkommit till följd av den tekniska utvecklingen. Marknadsföring via de nya kommunikationskanalerna har givit upphov till vissa olägenheter för mottagarna. Olägenheterna som mottagarna förorsakas vid marknadsföring via de nya teknikerna kan delas in i tre kategorier; 1) meddelandet förorsakar kostnader för mottagaren, 2) meddelandet hindrar mottagaren samt 3) meddelandet upplevs vara påträngande och utgöra ett intrång i mottagarens privatliv. Under de senaste åren har det förekommit hektiska lagstiftningsåtgärder på många håll i världen. Såväl enskilda stater, nationella myndigheter samt internationella organisationer har utarbetat regler om marknadsföring via de nya teknikerna. En av kärnfrågorna i regleringen är huruvida man skall ha ett system med ”opt-in” eller ”opt-out”. En opt-in-lösning innebär att marknadsföraren måste inhämta mottagarens samtycke på förhand, medan en opt-out-lösning innebär att det är tillåtet att sända marknadsföring om inte mottagaren motsatt sig detta. Enligt gällande lagstiftning faller marknadsföring via följande tre tekniker under opt-in: automatiserade uppringningssystem, telefax samt e-post. Det huvudsakliga syftet med avhandlingen är att utreda om nuvarande opt-in-lista är tillräckligt omfattande med beaktande av de olägenheter som marknadsföring via de nya teknikerna förorsakar, eller om den bör utvidgas. I genomgången av marknadsföring via nya tekniker har marknadsföring via bl.a. följande tekniker undersökts: Internet (www-sidor), reklamfönster, reklambanner, e-post, mobiltelefon, telefax, bloggar, RSS, Instant Messaging samt Internettelefoni. Vid sidan av nya tekniker har även vissa ”traditionella” marknadsföringsmetoder undersökts, i syfte att utreda huruvida även de bör falla in under en opt-in-lösning. De traditionella marknadsföringsmetoder som ingår i avhandlingen är hemförsäljning, telemarketing, TV- och radioreklam samt adresserad och oadresserad direktreklam. En annan central del i avhandlingen är frågan hur påföljdssystemet vid överträdelser av opt-in-bestämmelserna bör utformas. Hur skall de enskilda mottagarna få ersättning för de kostnader de åsamkats av marknadsföringen? Är det dags att införa straffskadestånd i Finland? Hög tid att även Finland får grupptalan? Kan tvisterna avgöras virtuellt via domstolar on-line eller ODR?

Nível de evidenciação obrigatória nas empresas de capital aberto: uma análise do CPC 27

O atendimento às informações obrigatórias que integram pronunciamentos emitidos por órgãos normativos vem sendo tema de estudos nacionais e internacionais, que buscam identificar os níveis de divulgação de determinados mercados ou setores da economia. Alinhado a este cenário, o objetivo do presente estudo é analisar o nível de evidenciação das demonstrações financeiras divulgadas no ano de 2012 pelas empresas listadas na Bolsa de Valores, Mercadorias e Futuros de São Paulo (BM&FBOVESPA) em relação aos requisitos exigidos no CPC 27, que estabelece o tratamento contábil para ativos imobilizados. Foi elaborado um índice para apurar o nível de cumprimento da divulgação, denominado de Índice de Não Divulgação (IND) que obteve 32,9% como resultado. Para identificar as características que poderiam influenciar o índice encontrado, foram desenvolvidas hipóteses atreladas ao porte da empresa, à emissão de American Depositary Receipt (ADR), à empresa de auditoria prestadora do serviço e ao segmento de mercado. Os testes de diferenças de média apontaram que todas as características utilizadas podem explicar o cumprimento das informações obrigatórias para ativo imobilizado. Para se alcançar o pleno atendimento aos requisitos obrigatórios, as empresas demandam um período de adequação, bem como para os reguladores do mercado ampliarem a orientação e fiscalização, adquirindo a confiabilidade das informações divulgadas.

何首乌炮制前后生物活性和化学成分的变化研究

何首乌为常用中药，由何首乌及含何首乌的中成药制剂所引起的不良反应也时见报道，科学阐明不良反应的物质基础并提出解决方案对何首乌的使用十分重要。本论文研究了何首乌炮制前后KM小鼠肝脏毒性基因表达谱、生物活性及化学成分的变化。所获结果支持何首乌炮制的目的是减毒、改性（改变药效），何首乌生、熟异治的观点。制首乌对抑郁症的效果显著优于生首乌，这与本草所记载的何首乌炮制后补肝肾、益精血，归肝、肾经一致。 主要结果如下： 1、 生、制首乌的毒理基因芯片研究结果 何首乌的不良反应主要表现在肝损害方面。本研究建立了生何首乌和制何首乌不同剂量的肝毒性作用模型，体重指标统计发现生何首乌各剂量组平均体重显著下降，中剂量组（10 g/kg.d）体重下降20 %，高剂量组（20 g/kg.d）体重下降42%，50%动物死亡，提示动物机体能量代谢障碍；基因芯片研究结果表明何首乌是CYP450的抑制剂，生何首乌相对于制何首乌CYP3A4、CYP4A5显著下调，导致毒性成分在体内的吸收增加，服用大剂量的生何首乌后产生明显的肝毒性；主要对以下六条Pathway产生影响：①PPAR signaling pathway，主要毒性靶基因有RXRB CYP7a1、Acadl、Apoa2、Cyp4a、 FABP2 、MAPKKK5等基因。②Calcium signaling pathway，主要毒性靶基因有CAMK2B、CACNA1F、S100A1、 F2R、Ryr1、Slc8a2、Camk4 ③Neuroactive ligand-receptor interaction，主要毒性靶基因有Chrm4、 Ntsr2 、 GABRR1、 GRIK3、F2R等基因。④Wnt signaling pathway，主要毒性靶基因有Daam2、Rac1 等基因。⑤Complement and coagulation cascades，主要毒性靶基因有F2R、Serpina1b、Cfi 、FGA等基因。⑥Oxidative hosphorylation，主要毒性靶基因有Atp5e、NDUFA1等基因。生何首乌毒性明显强于制首乌，且生何首乌水煎液的毒性大于生何乌首丙酮提取物的毒性，这一结果表明，何首乌主要的毒性成分很可能并不仅仅是传统所认为的以大黄素为代表的蒽醌类化合物，而是何首乌中大量存在的有效组分二苯乙烯苷与大黄素相互作用的结果，这一研究结果与前述的何首乌对肝药酶的影响是一致的。后续生、制首乌的化学成分差异研究表明，炮制后二苯乙烯苷含量明显降低：生首乌为5.512 %、清蒸制首乌为3.811 %、豆制首乌为3.538 %,大黄素的含量炮制后显著升高,生首乌为0.094 %、清蒸制首乌为0.119 %、豆制首乌为0.126 %。 2 生、制首乌药效差异研究结果 本文采用慢性中等强度不可预知应激刺激模型(chronic unpredictable mild stress, CUMS)和动物行为绝望实验法，研究生、制首乌抗抑郁活性的差异，制首乌（5 g/kg.d）与模型组相比有显著差异（P< 0.01），生首乌制首乌（5g/kg.d）与模型组相比无显著差异，这一结果表明制首乌抗抑郁活性显著优于生首乌。 本文比较了生、制首乌对四氧嘧啶糖尿病模型小鼠血糖的影响的差异，生首乌（5 g/kg.d）与模型组相比有显著差异（P< 0.01），制首乌（5 g/kg.d）与模型组相比无显著差异，这一结果表明生首乌降糖活性优于制首乌。这一结果与历代中医古书中生首乌治疗消渴症（糖尿病）的记载一致。 3生、制首乌化学成分差异的研究结果 本文选用HPLC-DAD指纹图谱技术结合药效成分含量测定来研究生、制首乌化学成分的差异。炮制后，何首乌中的主要化学成分并未消失，只是其含量发生了改变。炮制后二苯乙烯苷含量明显降低：生首乌为5.512 %、清蒸制首乌为3.811 %、豆制首乌为3.538 %,大黄素的含量炮制后显著升高,生首乌为0.094 %、清蒸制首乌为0.119 %、豆制首乌为0.126 %。 综上所述，炮制前后何首乌中二苯乙烯苷和大黄素含量比的变化可能是何首乌炮制减毒、改性的物质基础。 根据上述结果我们建立了生、制首乌的质量控制新模式。 In recent years, some adverse drug reactions (ADR) about some traditional Chinese medicine were reported at times. As a Chinese medicine most in use, the ADRs of Radix Polygoni multiflori (RPM) and the medicines containing the RPM were also mentioned. The resolution of the problems caused by the ADRs is very important for the use of the RPM as a medicine. The process (or preparation) is a significant feature for the clinical use of the Chinese medicine and an important technology for the safe use and good effect of the Chinese medicine. By processing, the toxicity of the Chinese medicine can be reduced, its properties can be changed and curative effect can be enhanced at the same time. The changes of the gene expression profiles for KM mice hepatotoxic effects, and the change of the biological activity and the chemical composition after being processed of the RPm were studied in the present dissertation. The RPm heatotoxicity mechanism and the toxicity target genes were explained on the gene level for the first time. With the antidepressant activity, and the hypoglycemic effect as the target, the differences on the pharmacodynamics between the processed RPm and unprocessed RPm, for the first time, were investigated. The results obtained show that the antidepressant activity of the processed RPM is far higher than the ones of unprocessed RPm. As we know, the results were reported for the first time. The quality control systems (QCS) for the processed and the unprocessed RPm were founded. The HPLC-DAD was used in the systems founded on the basis of the toxicology and the pharmacodynamics experiments. As we know, the OCSs were reported for the first time. The above-mentioned experimental results confirm that the unique process theory of the traditional Chinese medicine (TCM) used for the process of the Radix Polygoni multiflori (RPm) is correct, i.e after being processed the toxicity of the RPm decreases and its Pharmacodynamic effects change. It is known to author that there have been no similar reports in the literatures up to now. The main experimental results are summarized as follows: 1 The results on the mice toxicology gene chip for the unprocessed and processed RPm The KM mice hepatotoxic model caused by the RPm at the different dosages was established in the present study. The results obtained show that the mouse average body weight obviously decreased in the groups at the different dosages of the unprocessed RPm: the 10 g/kg.d .group decreased 20%; 20 g/kg.d. group decreased 42%, and 50% mice died at 20 g/kg.d. group. The main experimental results on the mice toxicology gene chip The RPm is the CYP450 inhibitor. As compared with the processd RPm, the CYP3A4, CYP4A5 of the unprocessed RPm demonstrate the marked downregulation, which leads to the increase of the poison absorbtion into the body with the result that the unprocessed RPm yields the marked hepatotoxication. The hepatotoxication was produced because the following 6 pathways were affected: ①PPAR signaling pathway, the chief toxicity target genes are RXRB, CYP7a1, Acadl, Apoa2, Cyp4a, FABP2 and MAPKKK5 etc. ②Calcium signaling pathway, the chief toxicity target genes are CAMK2B, CACNA1F, S100A1, F2R, Ryr1,Slc8a2 and Camk4 etc. ③Neuroactive ligand-receptor interaction, the chief toxicity target genes are Chrm4, Ntsr2, GABRR1, GRIK3 and F2R etc. ④Wnt signaling pathway, the chief toxicity target genes are Daam2, Rac1 etc. ⑤Complement and coagulation cascades, the chief toxicity target genes are F2R, Serpina1b, Cfi and FGA etc. ⑥Oxidative phosphorylation, the chief toxicity target genes are Atp5e, NDUFA1 etc. The above experimental results, for the first time , demonstrate on the gene level that the unprocessed Rpm toxicity is far stronger than the processed RPm one, and the toxicity of the water decoction of the unprocessed RPm is greater than the one of its acetone extracts, which shows that the chief toxicity components of the RPm are probably not only the anthraquinones, for example, the emodin, but the complex compounds produced by the interaction between the emondin and the stilbene glucoside which is the largest component of the unprocessed RPm. The result is accordance with the above effect of the RPm on the hepatic drugenzyme. Aftter being processed, in fact, the content of the stibene glucoside in the RPm markedly decreases. 2. The results on the pharmacodynamic differences between the unprocessed and processed RPm The results obtained show that the effects of processing on RPm pharmacodynamic behaviour received in the Chinese Material Medica are correct. It is known to author that this is the first experimental result in the research materials now available. The chief results are as follows: For the treatment of the antidepressant, the curative effect of the processed RPm is far better than the one of the unprocessed RPm. By contrast with the above results, the hypoblycemic effect of the unprocessed RPm is better than the one of the processed RPm. 3. The results on the Chemical Composition The results obtained by using HPLC-DAD fingerprint and by the determination of effective component content show that the main chemical components in the RPm after being processed do not disappear, but their contents change. The contents of the stilbene glucoside (SG) and emodin in the different samples were determined as follows: SG contents 5.512 % for the unprocessed RPm 3.811 % for the processed RPm (Steamed) 3.588 % for the processed RPm (black soybean) Emodin contents 0.094 % for the unprocessed RPm 0.119 % for the processed RPm (Steamed) 0.126 % for the processed RPm (black soybean) The combination of above experimental results on the toxicity, the pharmacodynamics and the chemical composition indicates that the changes of the content ratio of SG/emodin may be the substance base of the toxicity decrease and pharmacodynamic changes of the RPM by the processing.

Desempenho de clones de seringueira sob diferentes sistemas de sangria.

Este trabalho teve como objetivo avaliar o crescimento e a producao da borracha de clones seringueira [Havea brasiliensis ( Wild. Ex Adr. De Juss.) Muell. Arg.] sob diferentes sistemas de sangria, em condição de Cerrado dos Municipios de Barro Alto Goianesia no Estado de Goais. O plantio foi feito em fevereiro de 1992, no espacamento de 8,0 x 2,5 m (500 plantas/ha), em talhoes de 8 a 10 hectares para cada um dos clones RRIM 600, GT 1, PB 217, PB 235, PR 107 e PR 255 os quais receberam as mesmas praticas de manejo. Aos oito anos de idade, foram feitas as seguintes avaliacoes: estande final; circunferencia do caule a 1,20 m do solo; porcentagens de plantas aptas a sangria; producao de borracha acumulada na caneca pesada mensalmente; incidencia de seca de painel. A producao foi avaliada em nove sistemas de sangria em meia espiral (1/2 S), praticados cinco dias por semana (5d/7) e 10 meses ao ano (10m/12), variando na frequência de sangria (d/4 e d/7 = a cada 4 e 7 dias), a concentracao de Ethephon (ET 0,25%, 2,5%,3,3% e 5,0%) e sua frequencia de aplicacao durante o periodo chuvoso ( a cada 22, 28 e 35 dias), como segue: 1) 1/2S, d/7, ET 2,5% a cada 22 dias; 2)1/2S, d/7, ET 2,5% a cada 30 dias (referncia); 3) 1/2S. d/4, ET 2,5% a cada 30 dias; 4) 1/2S, d/7, ET 3,3% a cada 22 dias; 5)1/2S, d/7, ET 3,3% a cada 30 dias; 6) 1/2S. d/7, ET 5,0% a cada 22 dias 7) 1/2S, d/7, ET 5,0% a cada 30 dias; 8) 1/2S, d/7, ET 5,0% a cada 35 dias; 9) 1/2S, d/7, ET 0,25% (pulverizando 10 ml por painel) a cada 22 dias. Nos sistemas 1 a 8, o Ethephon foi pincelado ( 1mL) na canaleta de corte e ate 2 cm acima dela (Pa e La). O delineamento experimental foi de blocos ao acaso, com quatro repeticoes de 10 plantas poe parcela. Cada clone constitui um experimento separado, sendo os resultados de producao acumulada anual submetidos a analise de variancia e, nos caso de significancia, as medias dos sistemas foram comparadas pelo teste Tukey, ao nível de 5% de probabilidade. Nao foi constatada qualquer incidencia de seca de painel e os resultados possibilitaram as seguintes conclusoes para as condicoes da regiao: 1) o sistema 1/2S, d/7, ET 2,5% a cada 30 dias e o mais indicado par a sangria dos clones PR 255, PR 107, PB 235, PB 217 e GT 1; 2) o sistema 1/2S, d/7, ET 3,3% a cada 30 dias e o mais indicado para a sangria do clone RRIM 600; 3) a producao individual de borracha em kg/planta/ano e maior nos clones RRIM 600, PB 217 e PR 255, enquanto a producao total em kg/ha/ano e superior nos clones RRIM 600 e PB 235; 4)os clones PB 217 e PR 255 sao menos adaptados a regiao, apresentando menores valores de estande final, circunferencia do caule, porcentagem de plantas em sangria e de producao total de borracha por hectare.

Rozwiązywanie sytuacji konfliktowych w wymiarze jednostkowym i społecznym

O konflikcie jako zjawisku i procesie społecznym nigdy za wiele, zwłaszcza gdy w jednym tomie można znaleźć analizy teoretyczne źródeł i istoty konfliktu, jego konstruktywnego potencjału, jak i dysfunkcjonalności wobec relacji społecznych i społecznego ładu. Zagadnienia te omawiane są przez socjologów, pedagogów, psychologów, teoretyków prawa oraz praktyków zajmujących się ich rozwiązywaniem: pracowników socjalnych, terapeutów, mediatorów, negocjatorów, prokuratorów, sędziów, menedżerów. Oprócz diagnoz dotyczących sfer życia społecznego szczególnie zagrożonych konfliktem (stosunki międzynarodowe, sfera publiczna, edukacja i wychowanie) czytelnik znajdzie w książce opracowania na temat różnych dróg wychodzenia z konfliktu poprzez kompromis do konsensusu, z użyciem różnych narzędzi społecznych, takich jak: negocjacje, arbitraż, a zwłaszcza mediacje.

Pharmacotherapy optimization in older patients by a structured clinical pharmacist assessment and intervention

Introduction: Older individuals are particularly vulnerable to potentially inappropriate prescribing (PIP), drug related problems (DRPs) and adverse drug reactions (ADRs). A number of different interventions have been proposed to address these issues. However to-date there is a paucity of well-designed trials examining the impact of such interventions. Therefore the aims of this work were to: (i) establish a baseline PIP prevalence both nationally and internationally using the STOPP, Beers and PRISCUS criteria, (ii) identify the most comprehensive method of assessing PIP in older individuals, (iii) develop a structured pharmacist intervention supported by a computer decisions support system (CDSS) and (iv) examine the impact of this intervention on prescribing and incidence of ADRs. Results: This work identified high rates of PIP across all three healthcare settings in Ireland, 84.7% in the long term care, 70.7% in secondary care and 43.3% in primary care being reported. This work identified that for a comprehensive assessment of prescribing to be undertaken, an amalgamation of all three criteria should be deployed simultaneously. High prevalences of DRPs and PIP in older hospitalised individuals were identified. With 82.0% and 76.3% of patients reported to have at least one DRP or PIP instance respectively. The structured pharmacist intervention demonstrated a positive impact on prescribing, with a significant reduction MAI scores being reported. It also resulted in the intervention patients’ having a reduced risk of experiencing an ADR when compared to the control patients (absolute risk reduction of 6.8 (95% CI 1.5% - 12.3%)) and the number needed to treat = 15 (95% CI 8 - 68). However the intervention was found to have no significant effect on length of stay or mortality rate. Conclusion: This work shows that PIP is highly prevalent in older individuals across three healthcare settings in Ireland. This work also demonstrates that a structured pharmacist intervention support by a dedicated CDSS can significantly improve the appropriateness of prescribing and reduce the incidence of ADRs in older acutely ill hospitalised individuals.

Achieving continuous professional development in higher education

Traditional higher education technology emphasizes knowledge transmission. In contrast, the Community platform presented in this paper follows a social approach that interleaves knowledge delivery with social and professional skills development, engaging with others, and personal growth. In this paper, we apply learning and complex adaptive systems theory to motivate and justify a continuous professional development model that improves higher education outcomes such as placement. The paper follows action design research (ADR) as the research method to propose and evaluate design principles.

G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the alpha 1B-adrenergic receptor enhances mitogenesis and tumorigenicity.

The alpha 1B-adrenergic receptor (alpha 1B-ADR) is a member of the G-protein-coupled family of transmembrane receptors. When transfected into Rat-1 and NIH 3T3 fibroblasts, this receptor induces focus formation in an agonist-dependent manner. Focus-derived, transformed fibroblasts exhibit high levels of functional alpha 1B-ADR expression, demonstrate a catecholamine-induced enhancement in the rate of cellular proliferation, and are tumorigenic when injected into nude mice. Induction of neoplastic transformation by the alpha 1B-ADR, therefore, identifies this normal cellular gene as a protooncogene. Mutational alteration of this receptor can lead to activation of this protooncogene, resulting in an enhanced ability of agonist to induce focus formation with a decreased latency and quantitative increase in transformed foci. In contrast to cells expressing the wild-type alpha 1B-ADR, focus formation in "oncomutant"-expressing cell lines appears constitutively activated with the generation of foci in unstimulated cells. Further, these cell lines exhibit near-maximal rates of proliferation even in the absence of catecholamine supplementation. They also demonstrate an enhanced ability for tumor generation in nude mice with a decreased period of latency compared with cells expressing the wild-type receptor. Thus, the alpha 1B-ADR gene can, when overexpressed and activated, function as an oncogene inducing neoplastic transformation. Mutational alteration of this receptor gene can result in the activation of this protooncogene, enhancing its oncogenic potential. These findings suggest that analogous spontaneously occurring mutations in this class of receptor proteins could play a key role in the induction or progression of neoplastic transformation and atherosclerosis.