Years Of Delay Research Articles

Factors Influencing the Phenotypic Expression of Hypertrophic Cardiomyopathy in Genetic Carriers

Introduction and objectivesHypertrophic cardiomyopathy (HCM) is a disorder with variable expression. It is mainly caused by mutations in sarcomeric genes but the phenotype could be modulated by other factors. The aim of this study was to determine whether factors such as sex, systemic hypertension, or physical activity are modifiers of disease severity and to establish their role in age-related penetrance of HCM. MethodsWe evaluated 272 individuals (mean age 49 ± 17 years, 57% males) from 72 families with causative mutations. The relationship between sex, hypertension, physical activity, and left ventricular hypertrophy was studied. ResultsThe proportion of affected individuals increased with age. Men developed the disease 12.5 years earlier than women (adjusted median, 95%CI, –17.52 to –6.48; P < .001). Hypertensive patients were diagnosed with HCM later (10.8 years of delay) than normotensive patients (adjusted median, 95%CI, 6.28-17.09; P < .001). Individuals who performed physical activity were diagnosed with HCM significantly earlier (7.3 years, adjusted median, 95%CI, –14.49 to –1.51; P = .016). Sex, hypertension, and the degree of physical activity were not significantly associated with the severity of left ventricular hypertrophy. Adjusted survival both free from sudden death and from the combined event were not influenced by any of the exploratory variables. ConclusionsMen and athletes who are carriers of sarcomeric mutations are diagnosed earlier than women and sedentary individuals. Hypertensive carriers of sarcomeric mutations have a delayed diagnosis. Sex, hypertension, and physical activity are not associated with disease severity in carriers of HCM causative mutations.

Responses of sapwood ray parenchyma and non‐structural carbohydrates of Pinus sylvestris to drought and long‐term irrigation

Summary Non‐structural carbohydrates (NSC) play a crucial role in tree resistance and resilience to drought. Stem sapwood parenchyma is among the largest storage tissue for NSC in mature trees. However, there is a limited mechanistic understanding of how NSC reserves, stem parenchyma abundance and growth rates are interrelated, and how they respond to changing water availability. We quantified NSC, ray parenchyma abundance and ring width along four successive 5‐year radial sapwood segments of the stem of 40 mature Pinus sylvestris trees from a 10‐year irrigation experiment conducted at a xeric site in Switzerland. Percentage of ray volume (PERPAR) varied from 3·75 to 8·94% among trees, but showed low intra‐individual variability. PERPAR responded positively to irrigation with a lag of several years, but was unrelated to %NSC. %NSC was lower in wider rings. However, wider rings still contained a larger NSC pool that was positively related to next year's ring growth. Our results suggest that stem ray parenchyma does not limit NSC storage capacity, but responds to long‐term environmental drivers with years of delay. The observed carbon allocation patterns indicate a prioritization of storage over growth independent of growth conditions, likely as a mechanism to ensure long‐term survival. Furthermore, NSC pool size proved to be a determinant for the inter‐annual autocorrelation in tree‐ring growth. Our study highlights the importance of long‐term multi‐parameter studies to better understand tree responses to environmental variability at different time‐scales. A lay summary is available for this article.

Jak w Czechosłowacji pojmowano filmy Munka i Wajdy, czyli film w kontekście zawikłanej historii

Films of Polish Film School, the most signifi cant formation in post-war history of Polish cinema, appeared in Czechoslovakia with several years of delay. Power feared that their message will be dangerous for spectators. Meanwhile – for viewers they remain unknown or diffi cult to understand and only a few critics and fi lm historians could read them in accordance with the intentions of the directors Andrzej Munk and Andrzej Wajda, being the main representatives of the stream.

World chemical outlook

World chemical outlook

Late Nerve Repairs in Brachial Plexus Lesions

Objectives: It is a common opinion that surgical repair of brachial plexus later than 1 year from the lesion cannot lead to real functional results. This is probably true for repair by means of multiple grafts which need specially in root’s lesions a long time for reinnervation: This fact and the frequent delay in repair reduce in a substantial way the possibility to obtain good results in brachial plexus surgery. The continuous development of nerve transfers allowed shortening the time of recovery by means of very distal repairs, near to the mainly motor targets. The shortening of recovery time gives today the possibility to move forward the classical limits for nerve repair. Materials and Methods: The authors present the results obtained in 93 nerve transfers in 52 patients who underwent nerve repair after more than 1 year from the lesion. The series consists of 22 children with obstetric brachial plexus palsy and 30 adults with traumatic brachial plexus lesions all of them repaired after 1 year from the lesion with a maximum delay of 7 years. The nerve repaired by means of late transfers had been the suprascapular, the musculocutaneous, and the axillary. In all the cases, a previous electromyography detected the presence of fibrillation in the muscles that are planned to be reinnervated. Fibrillation is actually considered as a prerequisite to indicate a late nerve transfer. Results: Evaluation of results has been separate between children and adult patients. In adult patients, the results for biceps have been 30% of failures, 42% of partial results (M2/M3−), and 28% of good results (M3+/M4). The results for suprascapular have been 23% of failures, 45% of partial results, and 32% of good results. In children, the results for biceps have been 15% of failures and 85% of good results (&lt;M3+). The results for suprascapular have been 25% of failures, 25% of partial results, and 50% of good results. No result can be reported for deltoid due to the too reduced number of operated cases. Conclusions: Nerve transfers allow in a considerable number of cases to obtain functional results, in some case even after several years of delay. A part for late observed cases we can offer in this way a second option in cases of lack of recovery from primary surgery. Actually nerve transfer is nowadays a new possibility placed in between primary microsurgical repair and classic palliative surgery. Undoubtedly better results have been obtained in children, but surprisingly useful results could be obtained in adults even if in a more reduced percentage of cases.

Time, Death, and Retribution

The heart of a Lackey claim is that when a death row inmate is kept waiting too long for his execution, this delay can amount to cruel and unusual punishment — either because they delay is itself cruel and unusual, or because the execution on top of the delay is. All Lackey claims brought by death row inmates have failed, but not for want of trying. The usual complaint against Lackey claims is that those who, by their own appeals, delay their execution date cannot turn around and use that delay as an argument against their death sentences. I agree with other scholars that this argument is incorrect. However, even if it is true that prisoner choice cannot make an otherwise unconstitutional sentence constitutional, Lackey claims can — and should — fail if the courts adopt a certain theory of retribution, what I call “intrinsic desert retribution”. Examining that type of retribution, distinguishing it from other retributive theories, and showing how intrinsic desert retribution can refute most Lackey claims, is one of this article’s major contributions. In doing so, it breaks with most of the scholarly literature, which tends to be sympathetic to Lackey claims. But the fact that Lackey claims may survive given a certain theory of retribution does not make that theory something the state may permissibly pursue. And this is the second major contribution of the article: to make the case that retribution may in fact not be a permissible state purpose. In short, Lackey claims do not fail because they are too strong — they fail because they are not strong enough. The Supreme Court has traditionally held that the state may permissibly put someone to death because of retribution. But the Court has also said, in other contexts, that the state may not pursue certain aims. The state cannot promote religion, for one; nor can it adopt policies based solely on “animus” against a certain class of persons. My article suggests that when the state adopts retribution as a goal in capital punishment, and pursues that goal even after years of delay, then retribution starts to look more and more like something that, while it may be morally right, cannot be a goal the state can legitimately pursue.

Beyond special circumstances: climate change policy in Turkey 1992–2015

The contours of Turkey's climate policy have remained almost intact over the past two decades. Being an Annex I party without any mitigation commitments, Turkey maintains a peculiar position under UNFCCC. Subsequent to 12 years of delay in signing both the Framework Convention and the Kyoto Protocol, Turkey had the highest rate of increase in greenhouse gas emissions among the Annex I countries with 110.4% upsurge in the period 1990 and 2013. Yet with the new climate regime now in place, the country's mitigation pledges fall short of expectations both in terms of realistic projections and its ambition to step up in the post‐2020 period. Climate policies in Turkey, an EU candidate and OECD founding member with a growing economy, remain under‐investigated. Although the country has a wide range of policies and institutions in place, it shows limited progress in addressing climate change. Based on evidence from the literature, we observe that climate policies operationalize in Turkey insofar as they do not directly confront developmental ambitions, leaving policy diffusion with limited success. To provide a historic overview, we focus on climate policy development, actors, processes, and contemporary trends. Evidence shows that these are highly ridden with the politics of special circumstances: a notion that Turkey employs to refrain from bindings commitments. In order to go beyond special circumstances discourse, we argue the need for a bold policy shift in Turkey, a country subject to adverse impacts of climate change and high‐carbon lock‐in risk due to development policy preferences. WIREs Clim Change 2016, 7:448–460. doi: 10.1002/wcc.390This article is categorized under: Policy and Governance &gt; National Climate Change Policy

Bilingualism and Cognitive Reserve: A Critical Overview and a Plea for Methodological Innovations.

The decline of cognitive skills throughout healthy or pathological aging can be slowed down by experiences which foster cognitive reserve (CR). Recently, some studies on Alzheimer's disease have suggested that CR may be enhanced by life-long bilingualism. However, the evidence is inconsistent and largely based on retrospective approaches featuring several methodological weaknesses. Some studies demonstrated at least 4 years of delay in dementia symptoms, while others did not find such an effect. Moreover, various methodological aspects vary from study to study. The present paper addresses contradictory findings, identifies possible lurking variables, and outlines methodological alternatives thereof. First, we characterize possible confounding factors that may have influenced extant results. Our focus is on the criteria to establish bilingualism, differences in sample design, the instruments used to examine cognitive skills, and the role of variables known to modulate life-long cognition. Second, we propose that these limitations could be largely circumvented through experimental approaches. Proficiency in the non-native language can be successfully assessed by combining subjective and objective measures; confounding variables which have been distinctively associated with certain bilingual groups (e.g., alcoholism, sleep disorders) can be targeted through relevant instruments; and cognitive status might be better tapped via robust cognitive screenings and executive batteries. Moreover, future research should incorporate tasks yielding predictable patterns of contrastive performance between bilinguals and monolinguals. Crucially, these include instruments which reveal bilingual disadvantages in vocabulary, null effects in working memory, and advantages in inhibitory control and other executive functions. Finally, paradigms tapping proactive interference (which assess the disruptive effect of long-term memory on newly learned information) could also offer useful data, since this phenomenon seems to be better managed by bilinguals and it becomes conspicuous in early stages of dementia. Such considerations may shed light not just on the relationship between bilingualism and CR, but also on more general mechanisms of cognitive compensation.

Should living kidney donors with hypertension be considered for organ donation?

The large number of end-stage kidney disease patients waiting for a kidney transplant often means years of delay before a suitable organ becomes available. Living kidney donors are one way to circumvent such long waiting times, and the desire to increase the pool of living kidney donors has allowed the selection of donors with hypertension. Hypertensive kidney donors, despite having larger glomeruli, and fewer glomeruli, particularly when over the age of 50 years, do well in follow-up. The data are mainly in white living kidney donors whose preexisting hypertension has been well controlled [blood pressure (BP) <140/90 mmHg] on one or two antihypertensive medications. Those selected for donation do as well as nonhypertensive donors as long they are older (age >50 years), nonobese (BMI 26-30 kg/m), and have no evidence of end-organ damage prior to donation. Although the data supporting long-term safety of nephrectomy in hypertensive donors are modest, small studies with short-term follow-up suggest no increase in the incidence of kidney disease or worsening of the control of hypertension in donors with a history of high BP.

Labour under threat: The rise and (possible) fall of ‘collective bargaining in South China

INTERNATIONAL union rights Page 3 Volume 22 Issue 4 2015 FOCUS ❐ LABOUR SITUATION IN CHINA Labour under threat: The rise and (possible) fall of ‘collective bargaining’ in South China After at least three years of delay, the Guangdong Regulation on Collective Consultation and Collective Contract came into force in 1 January 2015 in this phenomenon has been on-going labour militancy and its role as a driver of state policy. Consequently, state policy has not been static in recent years. After at least three years of delay, the Guangdong Regulation on Collective Consultation and Collective Contract came into force in 1 January 2015. The ILO described the new regulation as heralding a ‘good year for business in Guangdong’ and argued that the new regulations provided a framework for collective bargaining. After years of lobbying aimed at reducing the impact of the regulations on Hong Kong business interests in Guangdong, The Hong Kong General Chamber of Commerce congratulated itself on getting all references to sector- and industry-level bargaining removed from the Regulations and raising the trigger threshold for demands for collective bargaining from a third to a half of all workers in an enterprise. The ACFTU has also been under pressure to react to labour unrest. Following the watershed 2010 strike by auto-parts workers employed in a Honda factory in Foshan, provincial and city levels of the organisation in Guangdong announced a willingness to experiment with various reforms with the potential to facilitate limited forms of collective bargaining. The two most important were pilots in the election of enterprise trade union committees that are largely appointed by management or higher trade unions; and the cautious emergence of annual collective bargaining in key industries, notably the auto industry and to a lesser extent at port terminals. Results to date have been mixed. In October 2013, university student researchers working undercover in factories wrote an open letter to the Shenzhen Federation of Trade Unions (SFTU) claiming that only two out the five factories they had worked in had effective elected union branches. Annual collective bargaining in Guangdong’s auto sector has been more interesting . Former chairman of the Guangzhou Federation of Trade Unions Chen Weiguang reported that the median negotiated pay rise in six Guangzhou-based wholly-owned auto parts factories was 15 percent for the period 2011-2012 and an average wage of RMB 3256 for frontline shop floor workers – excluding deputy supervisors and above – in 2013. In larger, more capital-intensive joint venture auto assembly plants, the median wage increase over the same period was 19 percent – but with higher differentials – and an average wage of RMB 5834. However, something of a stalemate has emerged over the last two years as state policy has swung back towards prioritising stability in the face of a generalised economic slowdown. On the one hand, the more repressive organs of the state have launched campaigns of intimidation and arrests against civil society actors such as the O n 3 December 2015, police began raiding the homes and offices of labour rights activists across the city of Guangzhou and the Pearl River Delta in China’s southernmost province of Guangdong. At least 21 people were taken in for questioning. Six have since been charged with gathering crowds to disrupt public order and one with embezzlement. They are facing prison sentences. Worse, there are rumours of the accusations being ‘upgraded’ to the much more serious charge of ‘threatening state security’. It carries a sentence of up to fifteen years in prison. In response, trade unionists, labour organisations , activists and academics have written articles and signed petitions calling for the release of the detainees. National union federations, Global Union Federations and the ITUC have contacted the party-led All China Federation of Trade Unions (ACFTU) expressing concern and calling for the organisation to intervene on behalf of the labour activists. Given the absence of transparency in China’s judiciary, the denial of regular access to lawyers and general climate of fear that this and previous crackdowns on lawyers and human rights defenders has created, on-going international solidarity is going to be a key resource for both detained activists and operational labour NGOs (LNGOs) in coming...

The Examination of the Ability of Earnings and Cash Flow in Predicting Future Cash Flows: Application to the Tunisian Context

This research aims to test the ability of accounting earnings versus cash flows to predict future cash flows in the Tunisian context. The study sample consists of 37 companies listed on the Tunisian financial market for the period 1998-2012. In this study, we provide evidence of the ability of accounting earnings and cash flows to predict cash flow for one and two subsequent years. The results show that for simple models whose variables of prediction is one or two years of delay, it is the operating cash flows that have the most interesting predictive capacity. However, for multi-year models, accounting earnings is most relevant in terms of predictive power of future cash flows.

Bipolar disorders following initial depression: Modeling predictive clinical factors

ObjectiveMost first lifetime episodes among persons eventually diagnosed with bipolar disorder are depressive, often with years of delay to a final differentiation from unipolar major depression. To support early differentiation, we tested several predictive factors for association with later diagnoses of bipolar disorder. MethodWith data from mood-disorder patients with first-lifetime episodes of major depression, we used multivariate, logistic modeling and Bayesian methods including Receiver Operating Characteristic curves to evaluate ability of one or more selected factors to differentiate patients who later met DSM-IV-TR diagnostic criteria for bipolar disorder and not unipolar major depressive disorder. ResultsWe analyzed data from 2146 patients (642 bipolar, 1504 unipolar) at risk for 13 years following initial depressive episodes. In multivariate modeling for 812 subjects with information on all clinical factors considered, seven significantly and independently differentiated bipolar from unipolar disorders, ranking (by significance): (a) ≥4 previous depressive episodes, (b) suicidal acts, (c) cyclothymic temperament, (d) family history of bipolar disorder, (e) substance-abuse, (f) younger-at-onset, or onset-age <25, and (g) male sex; four of these (c, d, f, g) can be identified at illness-onset. Bayesian analysis indicated optimal sensitivity and specificity at 2–4 factors/person and correct classification of 64–67% of cases, and ROC analysis of factors/person yielded a significant area-under-the-curve of 0.72 [CI: 0.68–0.75]. ConclusionsIn multivariate modeling, 7 factors were significantly and independently associated with bipolar disorder diagnosed up to 13 years after initial depression.

A rare infectious presentation of a temporal bone meningioma

To the Editor, En plaque meningiomas of the temporal bone commonly have years of delay in diagnosis due to the chronic nature of the presenting symptoms, which include serous otitis media and aural fullness, and the lack of compressive symptoms seen with bulky mass tumors [1]. We present a rare case of an en plaque temporal bone meningioma with an acute and critical presentation secondary to infectious processes that were a direct result of local invasion. Bacterial meningitis, brain abscess, and mastoiditis with secondary septic thrombosis were the salient presenting features in this case. This presentation is very atypical of temporal bone meningiomas, but failure to recognize these associations can result in missed diagnosis in critically-ill patients.

It's not your imagination: things you must know about anxiety, depression and other emotional disorders that affect one in every three individuals

When we seek to know more about the history of psychiatry and mental illness, we find at our disposal an eclectic set of readings: from the wise and deeply scientifically grounded book of Edward Shorter, the History of Psychiatry1, to the fantastic philosophical and archival development of Foucault with his History of Madness2. Despite the wide variety of speeches and opinions that these readings display, all of them strongly agree on one point: the stigma of mental illness has existed since time immemorial, long before the birth of the discipline psychiatry. One might mistakenly think that the issue of prejudice against mental disorders and against their bearers is a thing of the past, an issue of the Middle Ages, time of the famous witches hunt. Today, after nearly two hundred years of the existence of psychiatry and with so many discoveries about the brain, provided by neurosciences, the persistence of this sort of discrimination would be incompatible, once it derives from an archaic era. Nevertheless, this is a mistaken idea. If we look at the international literature on the stigma of mental illness, we can observe that every year increasingly more works are published from all over the world on the issue3. The Revista de Psiquiatria Clinica itself recently showed results from the first national study in Brazil about stigma4. In the current days it is clear, for example, that stigma causes immense losses to people with mental disorders: years of delay between onset of the disease and diagnosis, refusal to seek help to avoid discrimination, lack of treatment resources in the public health system and so on5. Once stigma is still present, persisting nowadays and being highly prejudicial, how do we fight it? Information. This is one of the most important tools in this fight. And information needs to be accurate, scientifically based and accessible to persons who have no technical knowledge about mental health issues6, 7. The authors Naiara Magalhaes and Jose Alberto de Camargo managed to achieve this goal uniquely with the work It’s not your imagination (Nao e coisa da sua cabeca). The opening chapter is one of the most robust and conceptually polished. “To begin with” (“Para comeco de conversa”) begins with a description of the situation of social invisibility of a person with mental disorder, a situation in which many people are. Figures are high and impressive: people live on average 13 years with depression before seeking treatment for the first time. At another point in the book figures rise to impressive 36 years when it comes about phobias. The authors point out the lack of information and stigma as important causes for this harm to persons. Through interviews with renowned professionals in the area of mental health in Brazil, authors then explain with stunning clarity how mental illness would be the result of social and biographical injuries allied to a “biochemically fertile soil”, the vulnerable brain. At the end of the chapter the book’s goals are stated: to clarify the tortuous paths by which our mind functions and to provide a “more peaceful coexistence with the diseases of the soul”.

Focus: European Works Councils after 20 years: taking stock

European Works Councils after 20 years: taking stock the Directive’s entry into force were exempted from any statutory requirements for the lifespan of the agreement, as long as they covered the entire workforce of the group. At the end of this ‘Article 13’ period (22 September 1996), about 480 companies used the possibility to conclude ‘Article 13’ agreements. About 30 MNCs had already had a European transnational information and consultation agreement even before the adoption Directive of 22 September 1994. So many negotiations within a relatively short period between 1994 and 1996 challenged many national trade unions and demanded a huge organisational effort by the European sectoral union organisations now know as the European Trade Union Federations (‘ETUFs’). Since 22 September 1996, negotiations to establish EWCs have been governed by the procedures under Article 6 of the 1994 Directive (and now under the recast Directive 2009/38/EC), which requires the formation of a Special Negotiation Body (‘SNB’). In principle, it is still up to the undertaking’s central management and the SNB to agree on the precise form and function of their EWC. This includes, for example, the signatory parties; coverage, composition, numbers and seat allocation; the terms of office; functions and procedure ; venue, frequency and duration of meetings ; issues for information and consultation; experts; confidentiality; employee-side pre-meetings , resources and facilities for EWCs, etc. Only if management and workers fail to agree, or if they so choose, is the ‘fall back solution’ specified in the Annex to the Directive and providing statutory minimum standards triggered off. The ETUI database (www.ewcdb.eu) identifies currently 1282 EWCs (November 2013) that have ever been created of which 1048 are still active. Some EWCs disappeared due to company mergers, acquisitions and other similar reasons. New beginning for EWCs: the recast Directive of 2009 Due to lack of precedent the 94/45/EC Directive was a kind of experiment. Thus, in Article 15 it foresaw a revision procedure to take place after three years allowing for future adjustments. After many years of delay caused by lack of initiative from the European Commission, discussions between the social partners driven mainly by trade union demands, on 6 May 2009 the European Parliament and the European Council under the so called recast procedure finally adopted an amended version of the EWC Directive. This new recast Directive was a compromise solution: it addressed many, but not all demands and problematic issues identified throughout the 13 years of operation of EWCs. Many European countries have industrial relations systems where works councils play a crucial role at enterprise level INTERNATIONAL union rights Page 20 Volume 20 Issue 4 2013 I n a globalised economy managerial decisions taken at the central level consider companies as transnational organisations in which national borders are of secondary meaning. On the other hand, worker representatives have for a long time acted on a national (or local) basis. Some provisional practical solutions to this mismatch started to emerge in the 1980s in multinational companies (‘MNCs’) headquartered in France, where group works councils begun inviting foreign workers’ representatives to their meetings on an informal and even formal basis. The first pre-Directive agreements were signed in the 1980s, but this became institutionalised in 1994 with the adoption of directive 94/45/EC on ‘Establishment of a European Works Council [‘EWC’] or a procedure in Community-scale undertakings and Community-scale groups of undertakings for the purposes of informing and consulting employees’ (the EWC Directive) The goal of the Directive has been to provide employees with the right to transnational information and consultation in companies acting in the EU and the European Economic Area (EU + Liechtenstein, Norway and Iceland). At the start, the United Kingdom opted out from the Directive, but joined in 1997 (Directive 97/75/EC). As any other European directive, also the EWC legislation had to be transposed into national legal order and the Member States had two years to do so. As a result on 22 September 1996, the EWC Directive became enforceable for workers, employers and trade unions. Today, all companies (including those headquartered outside of Europe, but having Community based operations) with at least 1000 employees within the...

Insurance for Insurance: Adapting the National Flood Insurance Program to the Challenges of the Present and the Future

The National Flood Insurance Program was created as a means to provide low-cost flood insurance and encourage responsible floodplain management while avoiding the costs associated with traditional disaster relief. However, outdated policies and poor management led to massive debt and programmatic shortcomings, and without major structural reform the program would fail, leaving millions underinsured. After years of delay and associated economic turmoil, Congress recently implemented a massive reform of the program and its policies in an attempt to ensure its near-term viability. These amendments address the majority of the issues raised by the public and the insurance industry, and constitute a significant and successful overhaul of an ailing program.

Many faces of angioedema

Angioedema of the intestinal tract is an infrequent but well-described cause of abdominal pain that can occur because of inherited, acquired, allergic, or drug-induced causes. Hereditary angioedema (HAE) is a genetic disorder that causes recurrent attacks of severe edema of various body parts, including the intestinal tract. Moderate to severe abdominal pain occurs in 43-93% of such attacks due to intestinal edema. Laryngeal edema is a potentially life-threatening manifestation. Failure to recognize and diagnose HAE or other causes of intestinal angioedema can lead to years of delay in diagnosis, and in the case of HAE, often to unnecessary abdominal surgeries. Recognizing the typical history of recurrent attacks of abdominal pain, oropharyngeal/laryngeal angioedema or cutaneous angioedema, family history of similar symptoms, association of attacks with stress or menses, and exacerbation of attacks after administration of estrogens or angiotensin-converting enzyme inhibitors will increase diagnostic accuracy. Interdisciplinary treatment is often necessary after the diagnosis of HAE, first with acute management in the emergency room or the intensive care unit, followed by either drug prophylaxis against future attacks using a C1-esterase inhibitor concentrate or attenuated androgens and discontinuation of medications known to trigger attacks. Newer drugs approved for treatment of acute attacks may have future roles in the prevention of attacks if further studies support their efficacy. Gastroenterologists in particular should maintain a high index of suspicion for the possibility of HAE or other causes of intestinal angioedema in patients with a history of recurrent abdominal pain.

Cognitive Chrono-Ethnography (CCE): a methodology for anticipating future user needs

This paper proposes Cognitive Chrono-Ethnography (CCE), a new study methodology for understanding people's in situ behavior selections in daily life. People select their next behavior to maximize their satisfaction for a given behavioral needs. They appropriately coordinate available cognitive resources to make the best decisions by using their knowledge of past experiences and by processing input from the environment and individual intrinsic state. When a study field is specified, CCE starts by defining critical parameters for understanding people's behavior by considering the nature of behavior selection processes in the field in question, and then designing ethnographical field observations by taking into account the fact that their results will be described in terms of the specified critical parameters. The participants' behavior is recorded, followed by a series of structured retrospective interviews for the purpose of describing their present behavior and obtaining their history of behavioral development. Analysis of the interview results aid in developing models of present behavior selections and their chronological changes in the past. These models serve as defining future needs of persons who follow the same developing paths with a certain amount of delay, e.g., a few years of delay. This paper describes a CCE study of spectators of professional baseball games at a ballpark who have become frequent visitors to a baseball stadium in 5 years.

Spondylarthropathies juvéniles : quels outils d’évaluation ? Quand débuter un traitement anti-TNF-α ?

Multiple evaluation tools (clinical, biological and radiological) are well defined and validated in ankylosing spondylitis and oligo/polyarthritis juvenile idiopathic arthritis (JIA). The specificity of juvenile spondyloarthropathy (JSpa) with peripheral joint involvement at onset and axial involvement occurrence during follow-up with some years of delay makes these tools imperfect to use in JSpa. Indeed BASDAI and BASFI only evaluate axial involvement and pediatric scores (ACRPedi, JADI, CHAQ) only peripheral joints. It is necessary to obtain a pediatric version of BASDAI and BASFI for further studies. In severe JSpa, refractory to NSAIDs (at least two different drugs), TNF-α antagonist therapy appears as an attractive option, also prospective studies are not yet available in this specific group of JIA. However, indication of TNF-α antagonists could be based on: persistent activity of more than three months despite NSAIDs (at least two); active joints more than two and ESR or CRP level above normal value.

A Third Seat at the Table: An Insider's Perspective on Patient Representatives

As the nation takes a fresh look at all aspects of medical care, advances in the health sciences--from genetic sequencing to stem cell technology--may give us opportunities to make health care better, faster, and more cost-effective. But first we must transform our approach to health care innovation, particularly in the regulation of new products that may signal clinical breakthroughs. These issues intersect at the table where federal agencies, particularly the Food and Drug Administration, and innovative product development companies negotiate the regulatory approval process. At present, both parties are overly constrained. The agencies face too many but what if? disincentives: potential and unknown safety risks and the specter of adverse publicity. The sponsors are wary of investing time and resources in the absence of a defined regulatory pathway. Too often, inaction seems the safest course. But for the people most directly impacted by disease, inaction is irresponsible, even unethical. Patients and their families have the greatest stake in the approval process. Their lives, and their quality of life, hang in the balance. They are in the best position to weigh actual risks and benefits. It is time to give patients, through carefully selected representatives, a seat at the regulatory approval table. If they serve as mediators, not just advisers, they can help regulators and companies identify new pathways for fostering innovation, building public trust, cutting costs, and addressing quality-of-life issues. Three decades of experience demonstrate that informed and dedicated representatives can break through development impasses. And since 2005, designated patient on the governing board of the California Institute for Regenerative Medicine (CIRM), which I have served on for the last four years, have shown that patients are uniquely qualified and motivated to help decide how medical products should be delivered responsibly and expeditiously. AIDS and the FDA Sea Change The concept of the representative came to prominence in the 1980s AIDS epidemic, which galvanized communities to unprecedented levels of scientific and political involvement. In the San Francisco Bay Area, advocates organized their own studies of HIV/AIDS drugs with local doctors and volunteer subjects. They conferred with pharmaceutical manufacturers and exerted pressure on the FDA and the National Institutes of Health. Their efforts helped bring about a sea change in AIDS clinical trials and drug regulation. The FDA revamped its approval criteria, and community advisory boards began working with institutions that received NIH AIDS-related grants. Starting in the 1990s, the FDA invited representatives to serve on advisory committees that review products for life-threatening diseases. But members typically occupy less than 10 percent of the slots on those committees, and they continually struggle to exert real influence on product decisions. After the FDA approved the multiple sclerosis drug Tysabri in 2004, manufacturers withdrew it when some patients in clinical trials developed a rare brain disease. Prolonged efforts by MS groups helped bring about the 2006 FDA reintroduction of the drug and a new government-industry program to educate patients about risks. As John Richert of the National Multiple Sclerosis Society said, We just have to learn ... how to balance those risks and benefits for each individual person who needs to be treated for their MS. (1) In 2007, an FDA advisory committee studying the prostate cancer drug Provenge endorsed its safety by a vote of seventeen to zero and its efficacy by a vote of thirteen to four. But the agency felt that it needed more data on safety and efficacy. Additional clinical studies resulted in several years of delay before approval was granted this past April. While the FDA may have been exercising due diligence in asking for further study, the delay caused an outcry from the national cancer community and was a key factor in the bipartisan introduction of the Access, Compassion, Care, and Ethics for Seriously Ill Patients (ACCESS) Act, legislation that is still pending in Congress. …