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PubMed2002

Before the paradigm shift: concepts and communication between doctors and nurses in a burns team.

The evolution of care delivered by a multidisciplinary burns team is a function of the effectiveness of the professional communication between team members. In this exercise, we have explored concepts and communication between nurses and doctors in a burns team. Loosely structured weekly meetings were held over a 4-month period. The explicit objective was to determine and define the current model of burns care in a regional burn centre. The implicit objective, however, was to develop a mutual appreciation of actual and potential problems in communication. Consensus task identification was achieved at the end of each meeting with full compliance in completing the tasks before the next meeting. Although there was a unanimous commitment to the team concept, traditional, professional, paradigms persist. For nurses, the concept of holistic modelling predominated, whilst the disease centred paradigm remained the focus of medical modelling. Linguistic, cultural and professional barriers to effective communication were identified but did not readily conform to prior expectations. Experience in burns care can transcend these barriers more effectively than a common culture or profession. In conclusion, team work and team building is a complex process that can benefit from an ongoing process of re-evaluation. An obvious yet common error is to assume a level of mutual understanding that does not in fact exist. Stepping aside to re-explore fundamental principles on which team members base their personal and professional practice can help in elucidating and determining new paradigms of care, which can be evaluated and appropriately implemented. The consensus conclusion was that this approach was a very valuable investment in time in pursuing excellence in the field of burns care.

Attitude of Health Personnel↗
PubMed2001

Radiation and germline mutation at repeat sequences: Are we in the middle of a paradigm shift?

Two assumptions are commonly made in the estimation of genetic risk: (1) that the seven specific loci in the mouse constitute a suitable basis for extrapolation to genetic disease in humans, and (2) that mutations are induced by radiation damage (energy-loss events leading to double-stranded damage) occurring within the gene and are induced linearly with dose, at least at low doses. Recent evidence on the mutability of repeat sequences is reviewed that suggests that neither of these assumptions is as well founded as we like to think. Repeat sequences are common in the human genome, and alterations in them may have health consequences. Many of them are unstable, both spontaneously and after irradiation. The fact that changes in DNA repeat sequences can clearly arise as a result of radiation damage outside the sequence concerned and the likely involvement of some sort of signal transduction process mean that the nature of the radiation dose response cannot be assumed. While the time has not come to abandon the current paradigms, it would seem sensible to invest more effort in exploring the induction of changes in repeat sequences after irradiation and the consequences of such changes for health.

Genetic Diseases, Inborn↗
PubMed2005

Paradigm shift in the treatment of head and neck cancer: the role of neoadjuvant chemotherapy.

Chemotherapy is an integral component of the management of patients with locally advanced head and neck cancer, though the optimal use of chemotherapy remains to be defined. The combination of a platinum agent and 5-fluorouracil has been used as the standard neoadjuvant treatment and has been shown to permit organ preservation in operable patients and improve long-term survival outcomes in operable and inoperable patients. Recently, the addition of a taxane, docetaxel or paclitaxel, to standard platinum plus 5-fluorouracil induction chemotherapy has been shown to further improve response rates and survival outcomes. Phase III data are emerging to support combinations of docetaxel or paclitaxel with a platinum plus 5-fluorouracil as a new, more effective and less toxic standard for neoadjuvant chemotherapy. Sequential treatment regimens, incorporating a combination of induction chemotherapy and chemoradiation, are also under study in efforts to further improve long-term survival outcomes. Induction regimens incorporating docetaxel or paclitaxel with a platinum plus 5-fluorouracil are under evaluation in this setting. Randomized trials comparing a sequential treatment approach with standard therapies are also being undertaken and will likely define a new treatment paradigm for patients with locally advanced head and neck cancer.

Antineoplastic Agents↗
PubMed2004

A paradigm shift in the nature of care provision in emergency departments.

OBJECTIVES: Access block to acute hospital inpatient beds has pressured emergency departments (EDs) to develop strategies to facilitate the management of patients in the community (new services) and to streamline ED care (facilitative initiatives). The aim of this study was to determine the nature and extent of those strategies introduced into the 17 public hospital EDs in Melbourne, Australia, since 1998. METHODS: This was a cross sectional survey of ED directors and/or nurse unit managers undertaken in November and December, 2002. Face to face or telephone interviews were conducted using a researcher administered questionnaire. RESULTS: All 17 EDs participated. A total of 15 strategies had been introduced into 15 (88.2%) EDs. New services included care coordination teams (12 ED, 70.6%), short stay units (10, 58.8%), psychiatric services (10, 58.8%), chest pain units (7, 41.2%), pharmacy services (3, 17.7%), sexual assault service (1, 5.9%), and hospital in the home within the ED (1, 5.9%). Facilitative initiatives included nurse initiated management (12, 70.6%), fast track processes (10, 58.8%), multidisciplinary triage (4, 23.5%), disposition nurses/communication clerks (3, 17.7%), and day treatment clinics (2, 11.8%). CONCLUSIONS: Melbourne's EDs have adapted rapidly to external pressures of access block and increasing patient numbers. Many traditional inpatient services have now been incorporated into the EDs. These EDs now provide a different and expanded paradigm of care.

Chest Pain↗
PubMed2006

Integrating POLST into palliative care guidelines: a paradigm shift in advance care planning in oncology.

Because predicting and outlining guidance for all possible scenarios is difficult, advance directives are rarely sufficiently precise to dictate patient preferences in specific situations as a disease progresses. Nonetheless, advance care planning is an essential process that should begin at the time of diagnosis, if not already initiated, to ensure that all patient and family rights are preserved. Communicating effectively with the patient and family and having the patient designate a surrogate decision-maker are critical. Attention must be paid to resolving conflicts among patient values and preferences and those of family and the health care team. Patient-centered goals for care and expectations should be elicited at first assessment and reassessed frequently as conditions change. As a disease progresses, advance directives are rarely precise enough to predict all possible scenarios and outline guidance for care. Therefore, for patients with advanced metastatic cancer and a potential life expectancy of less than 1 year, converting patient-centered treatment goals into actionable medical orders while the patient maintains capacity is a more effective way to ensure that patient preferences are honored. Physician Orders for Life-Sustaining Treatment (POLST) and similar medical order forms provide explicit direction about resuscitation status ("code status") if the patient is pulseless and apneic. POLST also includes directions about additional interventions the patient may or may not want. A decade of research in Oregon has proved that the POLST Paradigm Program more accurately conveys end-of-life preferences that are more likely to be followed by medical professionals than traditional advance directives alone.

Humans↗
PubMed2026

Paradigm shift for cry gene expression in Bacillus thuringiensis.

In most Bacillus thuringiensis strains, the cry genes are transcribed by RNA polymerases containing sporulation-sigma factors E or K, leading to the formation of an insecticidal crystal within the mother cell along spore development. The kurstaki HD1 strain, a parent of commercial strains, also releases the insecticidal proteins Cry1I and Vip3A in the extracellular medium. vip3A expression is activated by the transcriptional regulator VipR at the onset of the stationary phase. Here, we expanded the VipR regulon in strain HD1 by identifying the VipR-binding box upstream from the cry2Aa, cry2Ab, and cry1Ia genes, and conducting transcription assays. Unexpectedly, a VipR box was located in the promoter of a putative N-acetylmuramoyl-l-alanine amidase (ami) gene upstream from cry1Ac in strain kurstaki HD73, closely related to the HD1 but devoid of vipR. Introduction of vipR in this strain led to the expression of the ami-cry1Ac operon, resulting in an early and increased production of Cry1Ac. We demonstrated that Cry1Ac was also produced in a VipR-dependent manner in an HD73 ∆spo0A mutant. Similarly, an HD1 ∆spo0A strain produces all the insecticidal proteins encoded in its genome, including cry2Ab, previously considered unexpressed. A genomic analysis also revealed the presence of putative VipR-binding sequences in lepidopteran-active strains, upstream from cry genes such as cry1E, cry1F, cry9D, and cry9E. Overall, our results break the dogma on the regulation of cry1A and cry2A genes and provide evidence of sporulation-independent Cry toxin production in biopesticidal Bt strains.IMPORTANCEBacillus thuringiensis is a remarkably efficient entomopathogen due to its ability to produce various insecticidal proteins, such as Cry or Vip. This property has made it a highly effective biopesticide used worldwide. Our work modifies the paradigm of cry1 and cry2 genes being regulated solely by sporulation-specific sigma factors and thus exclusively expressed during this process. Indeed, we demonstrated that the VipR regulator controls the transcription of vip3Aa, cry2Aa, cry2Ab, cry1Ia, and the ami-cry1A operons encoded by a strain closely related to that of commercial biopesticides and specifically turns on their expression from the onset of the stationary phase, leading to the production of insecticidal crystals independently of sporulation. By providing new knowledge on the regulation of insecticidal protein genes, these findings bring new insight for the genetic improvement of Bt strains used as commercial biopesticides.

Bacillus thuringiensis↗
PubMed2002

Paradigm shifts in malaria parasite biochemistry and anti-malarial chemotherapy.

A fatty acid synthesis (FAS) pathway was recently discovered and established in the obligate human parasite Plasmodium falciparum. Its inhibition by triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) leads to its classification as a type II FAS. Humans, the vertebrate host for the malarial parasite utilize type I FAS, which is not inhibited by triclosan. This discovery thus paves the way for novel approaches to the treatment of malaria. In direct contrast to the delayed-death phenotype associated with poisoning of the apicoplast using certain other drugs, the rapid and striking action of triclosan suggests the possibility of developing new drug(s) for the treatment of malaria.

Animals↗
PubMed2003

Evolving questions and paradigm shifts in endoplasmic-reticulum-associated degradation (ERAD).

ER-associated degradation (ERAD) is a component of the protein quality control system, ensuring that aberrant polypeptides cannot transit through the secretory pathway. This is accomplished by a complex sequence of events in which unwanted proteins are selected in the ER and exported to the cytosol for degradation by the proteasome. Given that protein quality control can be essential for cell survival, it is not surprising that ERAD is linked to numerous disease states. Here we review the molecular mechanisms of ERAD, its role in metabolic regulation and biomedical implications, and the unanswered questions regarding this process.

Animals↗
PubMed2006

Palladium-catalyzed cross-coupling reactions of silanolates: a paradigm shift in silicon-based cross-coupling reactions.

This paper chronicles the conceptual development, proof of principle experiments, and recent advances in the palladium-catalyzed cross-coupling reactions of the conjugate bases of organosilanols. The discovery that led to the design and refinement of this process represents a classical illustration of how mechanistic studies can provide a fertile ground for the invention of new reactions. On the basis of a working hypothesis (which ultimately proved to be incorrect) and the desire to effect silicon-based cross-coupling without the agency of fluoride activation, a mild and practical palladium-catalyzed cross-coupling of alkenyl-, aryl-, and heteroaryl silanolates has been developed. The mechanistic underpinnings, methodological extensions, and the successful applications of this technology to the synthesis of complex molecules are described.

Butanols↗
PubMedDate not supplied

Paradigm shifts in clinical trials enabled by information technology.

The use of the world wide web for clinical trials changes the processes of performing clinical research in several fundamental ways. Greatly improved security, monitoring capability, and accuracy and timeliness of study conduct can be achieved while lowering cost. Data quality is enhanced while co-ordinating centre effort is reduced. The web provides a natural environment for linking the various components of clinical research, leading to new levels of simplicity and efficiency. It also enhances opportunities for recruitment of study investigators and patients. Other information technology tools and databases can be used to assist in this regard as well. Web-based trials change the relationship of the investigator site to the study and the site to the co-ordinating centre. Different roles and responsibilities lead to simplified processes and more and higher quality data. Many standard co-ordinating centre activities, such as randomization, protocol implementation and amending, document tracking, adverse event reporting, site monitoring, report generation and data analysis are all fundamentally changed in a web-based trial. Opportunities are enhanced to identify potential investigators and support their successful study conduct. As the role of investigator sites is changed in web-based research, more primary care medical providers can be attracted to research, providing more typical patients to studies than those sometimes available through more traditional research sites, especially those at academic study sites. Other activities can now be co-ordinated electronically with the advent of the web. The Institutional Review Board (IRB) can use online tools to control investigator participation, resulting in improved study efficiency and patient safety. A web-based research pharmacy provides tremendous efficiencies in managing and distributing study medications. Financial payments to the sites can be performed and recorded electronically, or even administered based on timeliness and quality of the data. Our early experience with web-based trials indicates that there can be tremendous gains in study efficiency and accuracy by restructuring processes, roles and responsibilities through a comprehensive centralized, web-based trial. The future appears bright for web-based clinical trials.

Clinical Trials as Topic↗