After a heart attack, patients often undergo a procedure to open up the clogged artery and install a tiny meshlike device called a stent to keep the artery propped open. In most cases, the body reacts to this foreign object with scar-tissue formation, and the artery narrows again. To combat this re-clogging process, National Institutes of Health inventors developed paclitaxel-coated stents and later licensed it to Angiotech. Approved by the Food and Drug Administration in March 2004, these stents are expected to substantially reduce the use of coronary artery bypass surgery, an expensive operation now performed annually on 350,000-plus Americans. This and three other examples of NIH licensing success stories are described in this paper: (a) Kepivance, which improves the quality of life for cancer patients by eliminating mouth sores, (b) AIDS drug ddI, an important component of many combination drug therapies, and (c) Vitravene, the first and only antisense drug to be approved by FDA. These four examples will illustrate the success not only of the NIH licensing program, but also the innovative approaches taken by NIH inventors and the persistence of its commercial partners. This paper also highlights the business and legal lessons learned from these four cases.
Other patients’ stories on the Internet can give patients information, support, reassurance, and practical advice.
We examined which search facility for online stories resulted in patients’ satisfaction and search success.
This study was a randomized controlled experiment with a 2x2 factorial design conducted online. We facilitated access to 170 stories of breast cancer patients in four ways based on two factors: (1) no versus yes search by story topic, and (2) no versus yes search by writer profile. Dutch speaking women with breast cancer were recruited. Women who gave informed consent were randomly assigned to one of four groups. After searching for stories, women were offered a questionnaire relating to satisfaction with the search facility, the stories retrieved, and impact of the stories on coping with breast cancer. Of 353 enrolled women, 182 (51.6%) completed the questionnaire: control group (n = 37), story topics group (n = 49), writer profile group (n = 51), and combination group (n = 45).
Questionnaire completers were evenly distributed over the four groups (χ2
3 = 3.7, P = .30). Women who had access to the story topics search facility (yes vs no): were more positive about (mean scores 4.0 vs 3.6, P = .001) and more satisfied with the search facility (mean scores 7.3 vs 6.3, P < .001); were more positive about the number of search options (mean scores 2.3 vs 2.1, P = .04); were better enabled to find desired information (mean scores 3.3 vs 2.8, P = .001); were more likely to recommend the search facility to others or intend to use it themselves (mean scores 4.1 vs 3.5, P < .001); were more positive about how retrieved stories were displayed (mean scores 3.6 vs 3.2, P = .001); retrieved stories that better covered their information needs (mean scores 3.0 vs 2.6, P = .02); were more satisfied with the stories retrieved (mean scores 7.1 vs 6.4, P = .002); and were more likely to report an impact of the stories on coping with breast cancer (mean scores 3.2 vs 2.9, P =. 02). Three main effects were associated with use of the writer profile search (yes vs no): being more positive about (mean scores 3.9 vs 3.6, P = .005) and more satisfied with the search facility (mean scores 7.1 vs 6.5, P =. 01), and being more positive about how retrieved stories were displayed (mean scores 3.8 vs 2.9, P < .001). For satisfaction with the search facility, an interaction effect was found (P = .03): at least one of the two search facilities was needed for satisfaction.
Having access to the story topics search facility clearly had the most positive effect on patient satisfaction and search success.
Breast cancer; life experiences; social support; Internet; information retrieval; patient satisfaction.
Numerous studies have examined low penetrance susceptibility polymorphisms in candidate genes, with some reporting significant findings. However, for the most part these associations could not be replicated in subsequent studies, suggesting that the original observations were due to chance. The failure to identify meaningful common genetic variation in relation to breast cancer should give us pause for thought and make us reconsider our current research strategies. The most recent directions of pooling samples to increase statistical power and pursuing whole genome screens may overcome some obstacles while also creating new challenges. Future studies should perhaps also consider alternative designs such as using surrogate (preferably continuous) markers of breast cancer, focusing on high-risk populations, and defining pathologically distinct outcomes.
Age is the most important risk factor for breast cancer; age is also a risk factor for undermanagement of breast cancer. We studied 1,859 women 65+ years of age with early stage breast cancer and found that undermanagement is a risk factor for recurrence and for dying of breast cancer. Although conservative treatment is likely warranted in patients with tumors having excellent prognostic characteristics and in women with very limited life expectancies, standard treatment is needed for the majority of older women if we are to reduce the disproportionate burden of breast cancer in this age group. We need better strategies for identifying those most likely to benefit from standard treatment and from systematic surveillance for recurrence. In this regard, collaboration between oncologists and primary physicians is essential for achieving high quality care and outcomes in this vulnerable group of patients.
Most of public health is based on the working hypothesis that disease is caused by exposure to noxious factors in the external environment. While this approach has produced great successes in primary prevention, a general theory of the origins of human disease cannot be found in the textbooks of public health or epidemiology. This paper suggests that, in all its manifestations, disease is a reaction of the human organism to, and/or a failure to cope with, one or more unbalancing changes in its internal environment. These are caused by one or more unfavourable exchanges with the external environment and/or failures in the structural and functional design of the organism. In the final analysis, human disease is attributable to the dependence of organisms on a fundamentally hostile external environment and to unfortunate evolutionary legacies. While this sketch of a theory suggests that there will ultimately be some hard limits to primary prevention, it also helps in identifying possible new approaches to prevention, including interfering with disease mechanisms, and remedying human organisms' design failures.
epidemiology; public health; disease aetiology; ecology; evolutionary biology
Examine the longitudinal effects of personal narratives about mammography and breast cancer compared with a traditional informational approach.
African American women (n=489) ages 40 and older were recruited from low-income neighborhoods in St. Louis, MO and randomized to watch a narrative video comprised of stories from African American breast cancer survivors or a content-equivalent informational video. Effects were measured immediately post-exposure (T2) and at 3- (T3) and 6-month (T4) follow-up. T2 measures of initial reaction included positive and negative affect, trust, identification, and engagement. T3 message-processing variables included arguing against the messages (counterarguing) and talking to family members about the information (cognitive rehearsal). T4 behavioral correlates included perceived breast cancer risk, cancer fear, cancer fatalism, perceived barriers to mammography, and recall of core messages. Structural equation modeling examined inter-relations among constructs.
Women who watched the narrative video (n=244) compared to the informational video (n=245) experienced more positive and negative affect, identified more with the message source, and were more engaged with the video. Narratives, negative affect, identification, and engagement influenced counterarguing, which in turn influenced perceived barriers and cancer fatalism. More engaged women talked with family members more, which increased message recall. Narratives also increased risk perceptions and fear via increased negative affect.
Narratives produced stronger cognitive and affective responses immediately, which in turn influenced message processing and behavioral correlates. Narratives reduced counterarguing and increased cognitive rehearsal, which may increase acceptance and motivation to act on health information in populations most adversely affected by cancer disparities.
mammography; breast cancer survivors; health communication; storytelling; narratives; cancer disparities
The philosophy behind personalized medicine is that each patient has a unique biologic profile that should guide the choice of therapy, resulting in an improved treatment outcome, ideally with reduced toxicity. Thus, there has been increasing interest in identifying genetic variations that are predictive of a drug’s efficacy or toxicity. Although it is one of the most effective drugs for treating breast cancer, tamoxifen is not effective in all estrogen receptor (ER)-positive breast cancer patients, and it is frequently associated with side effects, such as hot flashes. Relative resistance to tamoxifen treatment may be a result, in part, from impaired drug activation by cytochrome P450 2D6 (CYP2D6). Indeed, recent studies have identified allelic variations in CYP2D6 to be an important determinant of tamoxifen’s activity (and toxicity). This article will summarize the current information regarding the influence of the major genotypes and CYP2D6 inhibitors on tamoxifen metabolism, with a focus on its clinical utility and the current level of evidence for CYP2D6 genotyping of patients who are candidates for tamoxifen treatment.
MicroRNAs (miRNAs) are small noncoding RNAs with regulatory functions, which play an important role in breast cancer. Several studies have shown that miRNAs can act either as tumor suppressors or as oncogenes, and that measurement of miRNA expression in malignancies may have diagnostic and prognostic implications. This article highlights a series of three recent studies that prove the involvement of miRNAs in breast cancer metastases. The first proves that miR-10b indirectly activates the pro-metastatic gene RHOC by suppressing HOXD10, thus leading to tumor invasion and metastasis. The second proves that miR-373 and miR-520c can also promote tumor invasion and metastasis, at least in part by regulating the gene CD44. The third identifies miR-335, miR-206, and miR-126 as suppressors of breast cancer metastasis. Loss of miR-335 leads to the activation of SOX4 and TNC (encoding tenascin C), which are responsible for the acquisition of metastatic properties. Altogether, these remarkable findings are important for our understanding of malignant transformation in the breast and may have implications for the management of patients with advanced breast cancer. The use of miRNAs as anticancer therapeutic agents is promising, and such fine molecular studies certainly help in bringing miRNAs closer to clinical practice.
The bone is a very common site of metastasis in patients with advanced cancer. Skeletal metastases are most common in breast and prostate cancer, but virtually any advanced cancer may disseminate to the bone. On the basis of recent advances in the understanding of bone remodeling processes, denosumab, a fully human monoclonal antibody against RANK-L, has been developed. Phase III clinical trials have demonstrated that denosumab is well tolerated and effective in the treatment of bone loss and prevention of skeletal-related events in patients with bone metastases.
The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases—bone destruction was kept at bay a little longer. The next generation of bone metastasis treatments is well on its way in clinical development, and among them, the most advanced drug is denosumab. Denosumab is a fully human monoclonal antibody that inhibits osteoclast maturation, activation, and function by binding to receptor activator of nuclear factor kappa B ligand, with the final result being a reduced rate of bone resorption. In this review, we give an overview of relevant preclinical and clinical data regarding the use of denosumab in patients with solid tumors in general and prostate cancer in particular.
Denosumab; RANK ligand; Bone remodeling; Neoplasm; Metastasis; Monoclonal antibody; AMG 162
Compare the immediate affective and cognitive reactions to cancer survivor stories about mammography and breast cancer vs. a didactic, informational approach.
Participants (N=489) were African American women age 40 years and older (Mean = 61). Most had ≤ high school education (67%), annual household income ≤ $20,000 (77%), and a prior mammogram (89%). Participants completed surveys before and after watching the narrative or informational video. We used structural equation modeling to examine the large number of inter-related latent constructs.
Women who watched the narrative video experienced more positive and negative emotions, found it easier to understand the video, had more positive evaluations of the video, reported stronger identification with the message source (i.e., perceived similarity, trust, liking), and were more engaged with the video.
Narratives elicited immediate reactions consistent with theorized pathways of how communication affects behavior. Future studies should examine whether and how these immediate outcomes act as mediators of the longer-term effects of narratives on affect, cognitions, and behavior.
Stories of other women’s experiences may be more powerful than a didactic presentation when encouraging African American women to get a mammogram.
In May 2005, preliminary trial results pronouncing the effectiveness of Herceptin (trastuzumab) for treatment of early-stage breast cancer were disseminated at a high-profile scientific meeting. Herceptin was subsequently approved for use in the public healthcare systems of Canada and the United Kingdom, although the differences between the two decision timelines were stark. The authors compared UK and Canadian newspaper coverage of the Herceptin story to assess how it may have been “hyped” in each country. They analyzed a diverse sample of newspapers and coded clippings for reporters' framing of the drug's efficacy, costs and funding approval process. Canadian news coverage preceded formal publication of the trial results, while UK coverage mirrored major national events. Reporters in both countries used predominantly individualistic perspectives and framed Herceptin's efficacy in salutary terms. Framing of costs was more neutral in Canadian than in UK newspapers. Funding approval framing focused on inequitable access in the UK and timeliness in Canada. News coverage of drug access stories varies across jurisdictions in terms of intensity and some aspects of framing. Such variations likely reflect different journalistic practices and dominant political rhetoric. Greater attention should be given to the role that news coverage of drug access plays in shaping public opinion and policy action, especially when this coverage precedes scientific debate.
Despite the successful development of vaccines that are able to elicit potent and protective immune responses, the majority of vaccines were developed empirically and the mechanistic events leading to protective immune responses are often poorly understood. This impedes the development of new prophylactic as well as therapeutic vaccines for infectious diseases and cancer. Gaucher et al. took advantage of the effective yellow fever (YF) vaccine 17D (YF17D) to prospectively identify key immunological responses elicited by the vaccine using functional genomics and flow cytometric analysis. The results of the study clearly indicate ‘that the immune response to a strong vaccine is preceded by the coordinated induction of master transcription factors that lead to the development of a broad, polyfunctional and persistent immune response integrating all effector cells of the immune system’.
vaccine; functional genomics; immune response; yellow fever
Nutritional supplements can be a source of positive doping cases as some supplements contain prohibited substances without showing this on their label. This problem has existed for some time and has been extensively studied in the past 8 years. The sport of tennis has played a particular role in this problem because of some peculiar doping cases within its community.
This article focuses on this particular doping problem, explaining the background and reviewing the available literature. It presents the first 3 years of experience within the Netherlands Security System Nutritional Supplements Elite Sports (“Nederlands Zekerheidssysteem Voedingssupplementen Topsport” or NZVT) and explains the most extensive system established to combat this particular doping problem.
The NZVT experience has shown that paper‐based quality systems are still prone to possible contaminations, which leads to the conclusion that the best possible solution for athletes who wish to use nutritional supplements must include laboratory‐based analysis for doping substances, preferably repeated for every new batch. The most important educational message, however, is to use a nutritional supplement only if it is deemed of benefit by a nutritional expert.
doping; nutritional supplements; contamination
An international conference on Transposable Elements (TEs) was held 21–24 April 2012 in Saint Malo, France. Organized by the French Transposition Community (GDR Elements Génétiques Mobiles et Génomes, CNRS) and the French Society of Genetics (SFG), the conference’s goal was to bring together researchers from around the world who study transposition in diverse organisms using multiple experimental approaches. The meeting drew more than 217 attendees and most contributed through poster presentations (117), invited talks and short talks selected from poster abstracts (48 in total). The talks were organized into four scientific sessions, focused on: impact of TEs on genomes, control of transposition, evolution of TEs and mechanisms of transposition. Here, we present highlights from the talks given during the platform sessions. The conference was sponsored by Alliance pour les sciences de la vie et de la santé (Aviesan), Centre national de la recherche scientifique (CNRS), Institut national de la santé et de la recherche médicale (INSERM), Institut de recherche pour le développement (IRD), Institut national de la recherche agronomique (INRA), Université de Perpignan, Université de Rennes 1, Région Bretagne and Mobile DNA.
Chair of the organization committee
Abdelkader Ainouche, Mireille Bétermier, Mick Chandler, Richard Cordaux, Gaël Cristofari, Jean-Marc Deragon, Pascale Lesage, Didier Mazel, Olivier Panaud, Hadi Quesneville, Chantal Vaury, Cristina Vieira and Clémentine Vitte
Transposable elements; Evolution of transposable elements; Impact on genomes; Control of transposition; Mechanisms of transposition
The Indiana Tobacco Prevention and Cessation Agency (ITPC) was created in 2000 to address high tobacco use rates. This independent state agency, using Centers for Disease Control and Prevention (CDC) Best Practices for Comprehensive Tobacco Control Programs, administered a comprehensive program that supported community health coalitions and evidence-based public policy changes. From 2000 to 2011, ITPC operated in difficult budgetary and political environments and with less than 20% of the funding recommended by CDC. ITPC and its partners enabled social and cultural changes, reduced cigarette use rates, and increased the number of community smoke-free environments. Public health leaders in Indiana agreed that the independent agency model was effective in reducing the costs associated with tobacco-use-related disease and death. Despite broad public support for ITPC and its work, on April 29, 2011, the Indiana legislature passed a controversial budget bill that abolished the ITPC executive board and transferred its budget and function to the Indiana State Department of Health (ISDH). Although the tobacco control program is not insulated from political interference, the ISDH commissioner has created a new Tobacco Prevention and Cessation Commission, whose members report directly to him, with commitment to continue the programmatic focus of the former ITPC. Restoring full funding to the tobacco control program is necessary if Indiana's goal of decreasing the health care and business costs of tobacco use-related diseases are to be achieved.
One of the goals of the 2011 International Year of Chemistry is to celebrate the contributions of women to science. A question that has been frequently asked in this regard is... Why is it necessary to highlight women in the "age of equality"? The reasons are varied but the facts are that many women scientists worked in obscurity throughout the 19th and even well into the 20th century, sometimes publishing anonymously to be heard. This celebration of Women in Science is one way to recognize both the resiliency and passion of these women. As part of this celebration, Chemistry Central Journal's Thematic Series of "Women in Chemistry" includes this article describing the path several women took as they pursued chemistry careers spanning the latter part of the 20th century and into the early 21st century. Sharon Haynie, Nancy Jones, Cheryl Martin, Paula Olsiewski, Mary Roberts and Amber Hinkle each have unique story of their personal journey from childhood to adulthood. As you read these stories, listen generously, and feel free to share your own stories, comments and thoughts.
In the June 2011 issue of the New England Journal of Medicine, the BEAM (Bardoxolone Methyl Treatment: Renal Function in CKD/Type 2 Diabetes) trial investigators rekindled new interest and also some controversy regarding the concept of renoprotection and the role of renoprotective agents, when they reported significant increases in the mean estimated glomerular filtration rate (eGFR) in diabetic chronic kidney disease (CKD) patients with an eGFR of 20-45 ml/min/1.73 m2 of body surface area at enrollment who received the trial drug bardoxolone methyl versus placebo. Unfortunately, subsequent phase IIIb trials failed to show that the drug is a safe alternative renoprotective agent. Current renoprotection paradigms depend wholly and entirely on angiotensin blockade; however, these agents [angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)] have proved to be imperfect renoprotective agents. In this review, we examine the mechanistic limitations of the various previous randomized controlled trials on CKD renoprotection, including the paucity of veritable, elaborate and systematic assessment methods for the documentation and reporting of individual patient-level, drug-related adverse events. We review the evidence base for the presence of putative, multiple independent and unrelated pathogenetic mechanisms that drive (diabetic and non-diabetic) CKD progression. Furthermore, we examine the validity, or lack thereof, of the hyped notion that the blockade of a single molecule (angiotensin II), which can only antagonize the angiotensin cascade, would veritably successfully, consistently and unfailingly deliver adequate and qualitative renoprotection results in (diabetic and non-diabetic) CKD patients. We clearly posit that there is this overarching impetus to arrive at the inference that multiple, disparately diverse and independent pathways, including any veritable combination of the mechanisms that we examine in this review, and many more others yet to be identified, do concurrently and asymmetrically contribute to CKD initiation and propagation to end-stage renal disease (ESRD) in our CKD patients. We conclude that current knowledge of CKD initiation and progression to ESRD, the natural history of CKD and the impacts of acute kidney injury on this continuum remain in their infancy and call for more research. Finally, we suggest a new classification scheme for renoprotective agents: (1) the single-pathway blockers that block a single putative pathogenetic pathway involved in CKD progression, as typified by ACE inhibitors and/or ARBs, and (2) the multiple-pathway blockers that are able to block or antagonize the effects of multiple pathogenetic pathways through their ability to simultaneously block, downstream, the effects of several pathways or mechanisms of CKD to ESRD progression and could therefore concurrently interfere with several unrelated upstream pathways or mechanisms. We surmise that maybe the ideal and truly renoprotective agent, clearly a multiple-pathway blocker, is on the horizon. This calls for more research efforts from all.
Angiotensin receptor blockers; Angiotensin converting enzyme inhibitors; Renoprotection;
Diabetes mellitus; Chronic kidney disease; Revisionist view; Novel classification scheme; Renoprotective agents
Successful efforts to prevent health-care acquired infections occur daily in U.S. hospitals. However, few of these "success stories" are presented in the medical literature or discussed at professional meetings. Key components of successful prevention efforts include multidisciplinary teams, appropriate educational interventions, and data dissemination to clinical staff.
Prader–Willi syndrome (PWS) is well-known for its genetic and phenotypic complexities. Caused by a lack of paternally derived imprinted material on chromosome 15q11–q13, individuals with PWS have mild to moderate intellectual disabilities, repetitive and compulsive behaviors, skin picking, tantrums, irritability, hyperphagia, and increased risks of obesity. Many individuals also have co-occurring autism spectrum disorders (ASDs), psychosis, and mood disorders. Although the PWS 15q11–q13 region confers risks for autism, relatively few studies have assessed autism symptoms in PWS or directly compared social, behavioral, and cognitive functioning across groups with autism or PWS. This article identifies areas of phenotypic overlap and difference between PWS and ASD in core autism symptoms and in such comorbidities as psychiatric disorders, and dysregulated sleep and eating. Though future studies are needed, PWS provides a promising alternative lens into specific symptoms and comorbidities of autism.
Prader–Willi syndrome; Chromosome 15q11–q13; Autism; Psychosis
Despite intensive research, a treatment for diabetic patients that completely restores normoglycemia for an indefinite period of time remains elusive. Although islet transplantation temporarily confers normoglycemia to patients, the lack of a renewable source of insulin-producing β cells hampers the use of this treatment option. Although significant hurdles remain, recent advances in stem cell biology indicate that generation of fully matured β cells from uncommitted progenitor cells, including human embryonic stem cells and induced pluripotent stem cells derived from somatic cell populations, is becoming an achievable goal.
The lack of a renewable source of insulin-producing β cells hampers the use of islet transplantation to treat type 1 diabetes. But enormous advances have been made in generating such cells from human stem cell populations.
Primary biliary cirrhosis (PBC) is an autoimmune biliary disease characterized by injury of small and medium size bile ducts eventually leading to liver cirrhosis and death. While the causes remain enigmatic, recent evidence has strengthened the importance of genetic factors in determining the susceptibility to the disease. Besides the strong heritability suggested by familial occurrence and monozygotic twins concordance, for decades there has not been a clear association with specific genes, with the only exception of a low risk conferred by a class II human leukocyte antigen (HLA) variant, the DRB1*08 allele, at least in some populations. Only recently the story began to change when a strong protective associations between PBC and the HLA DRB1*11 and DRB1*13 alleles were found in Italian and UK series. But HLA genes fully returned to attract interest thanks to recent genome-wide association studies (GWAS) which clearly demonstrated that the major component of the genetic architecture of PBC are within the HLA region. As expected in a genetically complex disease, GWAS also identified several novel non-HLA variants, but it is to note that all of them are in immuno-related genes. In this review, the paradigmatic tale of what, and how, we learned about HLA genes in PBC will be retraced with particular focus on how GWAS are enabling us to rewrite the story of PBC pathogenesis. These recent discoveries will not only driving functional studies but will also held the promise of developing novel disease-specific treatments.
Human leukocyte antigens; genetics; autoimmune liver disease; etiopathogenesis
Liver transplantation (LT) from Donation after Cardiac Death (DCD) donors is increasingly being used to address organ shortages. Despite encouraging reports, standard survival metrics have overestimated the effectiveness of DCD livers. We examined the mode, kinetics and predictors of organ failure and resource utilization to more fully characterize outcomes after DCD LT.
We reviewed the outcomes for 32 DCD and 237 Donation after Brain Death (DBD) LT recipients at our institution.
Recipients of DCD livers had a 2.1 times greater risk of graft failure, a 2.5 times greater risk of re-listing, and a 3.2 times greater risk of re-transplantation compared to DBD recipients. DCD recipients had a 31.6% higher incidence of biliary complications and a 35.8% higher incidence of ischemic cholangiopathy (IC). IC was primarily implicated in the higher risk of graft failure observed after DCD LT. DCD recipients with IC experienced more frequent re-hospitalizations, longer lengths of stay, and required more invasive biliary procedures.
Related to higher complication rates, DCD recipients necessitated greater resource utilization. This more granular data should be considered in the decision to promote DCD LT. Modification of liver allocation policy is necessary to address those disadvantaged by a failing DCD graft.
This descriptive study examined problems and successes that a sample of 73 adult caregivers new to the role expressed in the first year of caring for stroke survivors. Data were collected from May 2002 to December 2005.
Bimonthly, trained telephone interviewers asked the participants open-ended questions to elicit their experience in caregiving. Guided by Friedemann’s framework of systemic organization, we analyzed the data using Colaizzi’s method of content analysis.
There were 2,455 problems and 2,687 successes reported. Three themes emerged from the problems: being frustrated in day-to-day situations (system maintenance in Friedemann’s terms), feeling inadequate and turning to others for help (coherence), and struggling and looking for “normal” in caring (system maintenance vs. change). Three themes were attributed to the successes: making it through and striving for independence (system maintenance), doing things together and seeing accomplishments in the other (coherence), and reaching a new sense of normal and finding balance in life (individuation and system maintenance).
These findings provided an in-depth, theory-based description of the experience of being a new caregiver and can help explain how caring can be a difficult yet rewarding experience. Knowledge of the changes over time allows health care professionals to tailor their interventions, understanding, and support.
caregivers; caring; problems; stroke; successes
Recent developments in information and communications technology have the potential to revolutionise health care. This has been recognised at government level, and plays a significant part in the new information strategy for the NHS "Information For Health". Telemedicine (literally, medicine at a distance) is one of the most successful techniques in this rapidly expanding field, and in preliminary studies has proved to be both successful and popular with patients and health care professionals. In the UK telemedicine has been mainly applied to two major areas of accident and emergency (A&E) practice. These are the transmission of computed tomography scans for urgent neurosurgical opinion and the ongoing support of minor injuries units. The latter also involves transmission and interpretation of radiographs, usually peripheral limb films.
Telemedicine is not a medical sub-specialty in itself, but a facilitator of all medical and surgical specialties. While recent modernisation initiatives have permitted A&E departments to purchase a range of telemedical equipment, overall progress is hampered by a lack of large or scientifically rigorous studies, and a complete absence of data on the economic implications of this new technique. This review introduces A&E telemedicine in terms that avoid jargon and complex technical details. After a brief consideration of the origins of the subject, attention is given to recent publications relating to minor injuries support and A&E teleradiology. The technical and clinical feasibility of A&E telemedicine are demonstrated, and a case is made for the transmission and interpretation of minor injuries radiographs using a relatively simple and inexpensive system, supported by timely radiological reporting. After a brief study of various legal and ethical issues, the likely developments of the future are discussed.
TGFβ signaling Smads (Smad2, 3, and 4) were suspected tumor suppressors soon after their discovery. Nearly two decades of research confirmed this role and revealed other divergent and cancer-specific functions including paradoxical tumor promotion effects. Although Smad4 is the most potent tumor suppressor, its functions are highly context-specific as exemplified by pancreatic cancer and head-and-neck cancer: in pancreatic cancer, Smad4 loss cannot initiate tumor formation but promotes metastases while in head-and-neck cancer Smad4 loss promotes cancer progression but also initiates tumor formation, likely through effects on genomic instability. The differing consequences of impaired Smad signaling in human cancers and the molecular mechanisms that underpin these differences will have important implications for the design and application of novel targeted therapies.
Fanconi Anemia; juvenile polyposis Smads; pancreatic cancer; squamous cell carcinomas; TGFβ signaling