bluuebunny/crossref_metadata_2025 huggingface dataset:
TRAIL/Apo2L ligand selectively induces apoptosis and overcomes drug resistance in multiple myeloma: therapeutic applications
Authors: Mitsiades Constantine S. , Treon Steven P. , Mitsiades Nicholas , Shima Yoshihito , Richardson Paul , Schlossman Robert , Hideshima Teru , Anderson Kenneth C.
Published: July 2002

Multiple myeloma (MM) remains incurable and novel treatments are urgently needed. Preclinical in vitro and in vivo evaluations were performed to assess the potential therapeutic applications of human recombinant tumor necrosis factor (TNF)–related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) in MM. TRAIL/Apo2L potently induced apoptosis of MM cells from patients and the majority of MM cell lines, including cells sensitive or resistant to dexamethasone (Dex), doxorubicin (Dox), melphalan, and mitoxantrone. TRAIL/Apo2L also overcame the survival effect of interleukin 6 on MM cells and did not affect the survival of peripheral blood and bone marrow mononuclear cells and purified B cells from healthy donors. The status of the TRAIL receptors (assessed by immunoblotting and flow cytometry) could not predict TRAIL sensitivity of MM cells. The anti-MM activity of TRAIL/Apo2L was confirmed in nu/xid/bg mice xenografted with human MM cells; TRAIL (500 μg intraperitoneally daily for 14 days) was well tolerated and significantly suppressed the growth of plasmacytomas. Dox up-regulated the expression of the TRAIL receptor death receptor 5 (DR5) and synergistically enhanced the effect of TRAIL not only against MM cells sensitive to, but also against those resistant to, Dex- or Dox-induced apoptosis. Nuclear factor (NF)-κB inhibitors, such as SN50 (a cell-permeable inhibitor of the nuclear translocation and transcriptional activity of NF-κB) or the proteasome inhibitor PS-341, enhanced the proapoptotic activity of TRAIL/Apo2L against TRAIL-sensitive MM cells, whereas SN50 reversed the TRAIL resistance of ARH-77 and IM-9 MM cells. Importantly, normal B lymphocytes were not sensitized to TRAIL by either Dox, SN50, or PS-341. These preclinical studies suggest that TRAIL/Apo2L can overcome conventional drug resistance and provide the basis for clinical trials of TRAIL-based treatment regimens to improve outcome in patients with MM.
Phase 1 study of polyethylene glycol formulation of interferon α-2B (Schering 54031) in Philadelphia chromosome–positive chronic myelogenous leukemia
Authors: Talpaz Moshe , O'Brien Susan , Rose Esther , Gupta Samir , Shan Jianqin , Cortes Jorge , Giles Francis J. , Faderl Stefan , Kantarjian Hagop M.
Published: July 2002

Interferon α (IFN-α) therapy improves prognosis in Philadelphia chromosome (Ph)–positive chronic myelogenous leukemia (CML). Polyethylene glycol (PEG) attached to IFN-α prolongs its half-life and may offer better therapy. The aims of this phase 1 study were to define the maximal tolerated dose (MTD), dose-limiting toxicities (DLTs), and response with PEG IFN-α-2b. Twenty-seven adults with Ph+ CML in chronic or accelerated phases, in whom IFN-α treatment had failed, were studied. Patients had hematologic (9 patients) or cytogenetic resistance (12 patients) or intolerance to IFN-α (6 patients). PEG IFN-α-2b was given as a weekly subcutaneous injection starting at 0.75 μg/kg weekly and escalating to 1.5, 3, 4.5, 6, 7.5, and 9.0 μg/kg. The MTD was defined at 7.5 to 9 μg/kg; DLT included severe fatigue, neurotoxicity, liver function abnormalities, and myelosuppression. Longer administration of PEG IFN-α-2b resulted in chronic side effects not observed earlier, which defined the MTD and DLT. The proposed phase 2 dose of PEG IFN-α-2b was 6 μg/kg weekly. Among 19 patients with active disease, 7 (37%) achieved complete hematologic response (CHR); 2 (11%) had a cytogenetic response (complete). Among 8 patients treated in CHR, 7 (87%) improved cytogenetic response to complete (4 patients) or partial (3 patients). All 6 patients intolerant to IFN-α tolerated PEG IFN-α-2b; 4 improved their cytogenetic response. The results show that PEG IFN-α-2b is easier to deliver (once weekly), better tolerated, and perhaps more effective than IFN-α.
Molecular pathways in bone marrow homing: dominant role of α4β1 over β2-integrins and selectins
Authors: Papayannopoulou Thalia , Priestley Gregory V. , Nakamoto Betty , Zafiropoulos Vivian , Scott Linda M.
Published: July 2002

The specific retention of intravenously administered hemopoietic cells within bone marrow is a complex multistep process. Despite recent insights, the molecular mechanics governing this process remain largely undefined. This study explored the influence of β2-integrins on the homing to bone marrow and repopulation kinetics of progenitor cells. Both antifunctional antibodies and genetically deficient cells were used. In addition, triple selectin-deficient mice were used as recipients of either deficient (selectin or β2) or normal cells in homing experiments. The homing patterns of either β2 null or selectin null cells into normal or selectin-deficient recipients were similar to those of normal cells given to normal recipients. Furthermore, spleen colony-forming units and the early bone marrow repopulating activity for the first 2 weeks after transplantation were not significantly different from those of control cells. These data are in contrast to the importance of β2-integrin and selectins in the adhesion/migration cascade of mature leukocytes. The special bone marrow flow hemodynamics may account for these differences. Although early deaths after transplantation can be seen in recipients deficient in CD18 and selectin, these are attributed to septic complications rather than homing defects. However, when β2- or selectin-null donor cells are treated with anti-α4 antibodies before their transplantation to normal or selectin-deficient recipients, a dramatic inhibition of homing (>90%) was found. The data suggest that the α4β1/vascular cell adhesion molecule-1 pathway alone is capable of providing effective capture of cells within the bone marrow, but if its function is compromised, the synergistic contribution of other pathways, that is, β2-integrins or selectins, is uncovered.
In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome
Authors: Cassinat Bruno , Chevret Sylvie , Zassadowski Fabien , Balitrand Nicole , Guillemot Isabelle , Menot Marie-Laurence , Degos Laurent , Fenaux Pierre , Chomienne Christine
Published: July 2002

Acute promyelocytic leukemia (APL) blasts possess a unique sensitivity to the differentiating effects of all-transretinoic acid (ATRA). Multicenter trials confirm that the combination of differentiation and cytotoxic therapy prolongs survival in APL patients. However relapses still occur, and exquisite adaptation of therapy to prognostic factors is essential to aim at a possible cure of the disease. A heterogeneity was previously reported in the differentiation rate of patients' APL blasts, and it was postulated that this may reflect the in vivo heterogeneous outcome. In this study, it is demonstrated that patients of the APL93 trial whose leukemic cells achieved optimal differentiation with ATRA in vitro at diagnosis had a significantly improved event-free survival (P = .01) and lower relapse rate (P = .04). This analysis highlights the importance of the differentiation step in APL therapy and justifies ongoing studies aimed at identifying novel RA-differentiation enhancers.
The impact of gender in oral proficiency testing
Authors: O’Loughlin Kieran
Published: July 2002

To date, the role of gender in speaking tests has received limited attention in language testing research. It is possible in oral interviews, for instance, that both interviewing and rating may be highly gendered processes. In tests like the IELTS interview, where the interviewer also acts as the rater, this poses the question of whether a gender effect, if it exists, stems from the interview itself, the rating decision or a combination of both these ‘events’. The data collected for this study consisted of the audio-taped performances of 8 female and 8 male test-takers who undertook a practice IELTS interview on two different occasions, once with a female interviewer and once with a male interviewer. The interviews were transcribed and analysed in relation to previously identified features of gendered language use, namely overlaps, interruptions and minimal responses. The scores later assigned by 4 raters (2 males and 2 females) to each of the 32 interviews were also examined in relation to the gender of both raters and test-takers using multi-faceted Rasch bias analyses. The results from both the discourse and test score analyses indicated that gender did not have a significant impact on the IELTS interview. These findings are interpreted in relation to more recent thinking about gender in language use.
Early experience with a new technique and technology designed for the study of pulsatile cardiopulmonary bypass in the rat
Authors: Gourlay Terence , Ballaux Philippe K , Draper Edward RC , Taylor Kenneth M
Published: July 2002

The benefits of pulsatile flow during the period of cardiopulmonary bypass (CPB) applied during open-heart surgery remains controversial. We have developed a rodent (rat) model of CBP that has been designed to functionally mimic the clinical setting, principally, but not solely, for the study of pulsatile CPB. The successful development of this model centres on the design of the bypass circuitry and the surgical approach employed. The entire circuit is similar to clinical equipment in terms of its construction, configuration, performance, material surface area to blood volume ratio, and priming volume to blood volume ratio. The overall priming volume of the perfusion circuitry is less than 12 ml. Early studies confirm that the pumping technology functions well, gas exchange was adequate at all times, and blood pressure exhibited a normal CPB profile and haemodynamic response to pulsatile blood flow. We conclude that this is an effective tool for investigating the pathophysiology of pulsatile blood flow during CPB.
Ef” cacy of two forms of electrical stimulation in increasing quadriceps strength: a randomized controlled trial
Authors: Bircan Cigdem , Senocak Ozlem , Peker Ozlen , Kaya Aylin , Tamc Sebnem Akgol , Gulbahar Selmin , Akalin Elif
Published: July 2002

Objective: To investigate whether electrical stimulation is effective in improving quadriceps strength in healthy subjects and to compare interferential and low-frequency current in terms of the effects on quadriceps strength and perceived discomfort.

Design: Randomized, controlled study.

Setting: Physical Medicine and Rehabilitation Department in a university hospital.

Subjects: Thirty medical faculty students, divided into three groups, participated in the study.

Interventions: Group A received electrical stimulation with bipolar interferential current while group B received electrical stimulation with lowfrequency current (symmetrical biphasic). Group C served as the control group. Electrical stimulation was given for 15 minutes, ”ve days a week for three weeks, at a maximally tolerated intensity with the knee fully extended in the sitting position.

Main outcome measures: Before and after the study, quadriceps strength was measured with a Cybex dynamometer isokinetically at the angular velocities of 60°/s and 120°/s. The perceived discomfort experienced with each type of electrical stimulation was quantified by the use of a visual analogue scale (VAS).

Results: Statistically significant increase in isokinetic strength was observed after training in group A and group B. Increase in strength did not differ between the stimulation groups. No significant change in strength occurred in group C. Perceived discomfort by the stimulation groups was not significantly different.

Conclusion: Both interferential and low-frequency currents can be used in strength training with the parameters used in this study.
The immediate effect of handling technique on range of movement in the hemiplegic shoulder
Authors: Tyson S F , Chissim C
Published: July 2002

Purpose: To assess the immediate effect of two different handling techniques on range of ‘exion in the hemiplegic shoulder.

Method: A randomized controlled design with within-subject comparison was used. Range of shoulder ‘exion was measured using a bubble goniometer. Range of passive movement was compared as the weak arm was lifted using an ‘axilla hold’ (when the gleno-humeral joint is supported and held in external rotation) and a ‘distal hold’ (when the arm is lifted at the forearm without shoulder support). Twenty-two people with arm weakness following stroke were recruited. They were inpatients or attending a day hospital in two NHS trusts, with no previous limitation of range or function of their arm. A paired t-test was used for analysis.

Results: Mean shoulder ‘exion for the axilla hold was 115.2 degrees (SD 38.45), and 97.7 degrees (SD 44.7) for the distal hold. This difference was signi”cant at p < 0.001 (95% con”dence interval (95% CI) 7.96, 26.88).

Conclusions: Lifting the hemiplegic arm by holding the humerus under the axilla and maintaining external rotation produces greater range of ‘exion at the hemiplegic shoulder than a ‘distal hold’.
Shoulder pain after stroke: a review of the evidence base to inform the development of an integrated care pathway
Authors: Turner-Stokes Lynne , Jackson Diana
Published: July 2002

Background: Shoulder pain is a common complication of stroke. It can impede rehabilitation and has been associated with poorer outcomes and prolonged hospital stay. This systematic review was undertaken to inform the development of an evidence-based integrated care pathway (ICP) for the management of hemiplegic shoulder pain (HSP).

Aims and objectives: 1) To provide a background understanding of the functional anatomy of the shoulder and its changes following stroke. 2) To review the literature describing incidence and causation of HSP and the evidence for factors contributing to its development. 3) To appraise the evidence for effectiveness of different interventions for HSP.

Methods: Data sources comprised a computer-aided search of published studies on shoulder pain in stroke or hemiplegia and references to literature used in reviews (total references = 121).

Main findings: Although a complex variety of physical changes are associated with HSP, these broadly divide into ‘flaccid’ and ‘spastic’ presentations. Management should vary accordingly; each presentation requiring different approaches to handling, support and intervention. (1) In the ‘accid stage, the shoulder is prone to inferior subluxation and vulnerable to soft-tissue damage. The arm should be supported at all times and functional electrical stimulation may reduce subluxation and enhance return of muscle activity. (2) In the spastic stage, movement is often severely limited. Relieving spasticity and maintaining range requires expert handling; overhead exercise pulleys should never be used. Local steroid injections should be avoided unless there is clear evidence of an in‘ammatory lesion.

Conclusions: HSP requires co-ordinated multidisciplinary management to minimize interference with rehabilitation and optimize outcome. Further research is needed to determine effective prophylaxis and document the therapeutic effect of different modalities in the various presentations. Development of an integrated care pathway provides a reasoned approach to management of this complex condition, thus providing a sound basis for prospective evaluation of different interventions in the future.
Lack of concealment may lead to selection bias in cluster randomized trials of palliative care
Authors: Jordhùy M S , Fayers P M , Ahlner-Elmqvist M , Kaasa S
Published: July 2002

Comprehensive palliative care programs are often implemented on a community level, and to evaluate such interventions, randomization by cluster (community) may be the only feasible method. In trials randomizing individual subjects, the importance of proper concealment has been stressed. In cluster randomized trials, however, concealment of individual patient allocation is often impossible. The following risk of selection bias has been given little attention. In the present study, comparing palliative care to conventional care, community health care districts were defined as clusters and randomized. The patients' treatment assignment was determined by the allocation of the cluster in which they resided, and hence predictable by their address. A biased selection based on practical considerations related to patients' diagnoses and hospital departments was suspected. To explore this, cancer diagnoses were grouped according to local tradition for sharing of treatment responsibility among hospital departments. A significant difference between trial arms in distribution of these groups was revealed and strongly supported our suspicion. The finding carries an important message to future researchers: when using cluster randomization, any evidence of selection bias should be carefully checked and reported.
Calving glaciers
Authors: van der Veen C. J.
Published: July 2002

Based on a review of observations on different types of calving glaciers, a simple calving model is proposed. Glaciers that exist in a sufficiently cold climate can form floating ice shelves and ice tongues that typically do not extend beyond confinements such as lateral fjord walls or mountains, and ice rises. If the local climate exceeds the thermal limit of ice shelf viability, as is the case for temperate glaciers, no floating tongue can be maintained and the position of the terminus is determined by the thickness in excess of flotation. If the snout is sufficiently thick, a stable terminus position at the mouth of the confining fjord - usually marked by a terminal shoal - can be maintained. Further advance is not possible because of increasing sea-floor depth and diverging flow resulting from lack of lateral constraints. If a mass balance deficiency causes the terminal region to thin, retreat is initiated with the calving front retreating to where the thickness is slightly in excess of flotation. In that case, the calving rate is determined by glacier speed and thickness change at the glacier snout. Advance or retreat of the calving front is not driven by changes in the calving rate, but by flow-induced changes in the geometry of the terminal region. This model is essentially different from prior suggestions in which some empirical relation - most commonly the water-depth model - is used to calculate calving rate and the rate of retreat or advance of the terminus.
Holocene land degradation and climatic change in northeastern Iceland
Authors: Ólafsdóttir Rannveig , Guòmundsson Hjalti J.
Published: July 2002

The spatial and temporal pattern of land degradation in northeastern Iceland during the Holocene is analysed in relation to climatic fluctuations. Tephrochronology is used to date the inferred terrestrial changes, and remote sensing and geographical information systems to assess the dynamic relationships between topographic relief, geomorphic processes and soil structure. Changes in vegetation and soil cover during the Holocene are found to be more dynamic than previously reported, highlighted by three substantial degradation phases, two of which occurred prior to the recorded Viking settlement in the ninth century AD, c. 5000 BP and c. 2500 BP. The results demonstrate the role of climate in modifying land cover, hence triggering land degradation without anthropogenic influence. However, anthropogenic activity probably had a significant role in the acceleration of the third degradation phase in the sixteenth century AD, when the system was possibly forced beyond its threshold of recovery, resulting in land degradation on a catastrophic scale.
Holocene vegetation history from the Salym-Yugan Mire Area, West Siberia
Authors: Pitkänen Aki , Turunen Jukka , Tahvanainen Teemu , Tolonen Kimmo
Published: July 2002

The pollen stratigraphy of an ombrotrophic patterned ridge-hollow raised bog in the Salym-Yugan Mire Area in boreal West Siberia (60°109N, 72°509E) covers the entire Holocene period. Pollen data from three parallel peat cores suggest that, contrary to previous assumptions, Betula forests did not spread into tundra until the Boreal period (9000–10000 cal. BP). After 9000 cal. BP, Pinus sylvestris and Picea abies forests displaced Betula forests in the area and dominated until 4100–4300 cal. BP, when Picea decreased considerably due to a climatic change and Pinus sylvestris became the most abundant tree species. Average pollen influx estimates during the wooded period, from about 9000 cal. BP onwards, were 5600–6350 grains cm–2 yr–1, similar to pollen-trap estimates from boreal coniferous forests.
Holocene changes in atmospheric circulation recorded in the oxygen-isotope stratigraphy of lacustrine carbonates from northern Sweden
Authors: Hammarlund Dan , Barnekow Lena , Birks H. J.B. , Buchardt Bjørn , Edwards Thomas W.D.
Published: July 2002

The oxygen-isotope composition of local precipitation (d18OP) is reconstructed from carbonate lake-sediment components in a sediment core covering the last 10000 calendar years from Lake Tibetanus, a small, hydrologically open, groundwater-fed lake in the Abisko area, northern Sweden. Comparison of the d18OP history with a pollen-based palaeotemperature record from the same core clearly reveals pronounced deviations from the normally expected temporal d18OP-temperature relation (so-called ‘Dansgaard relation’) that may be a function of changing oceanicity. The transition from relatively moist, maritime conditions in the early Holo cene to a much drier climate after 6500 cal. BP is re‘ ected by major changes in forest extent and composition as recorded by pollen and plant macrofossil data. At the time of maximum in‘ uence of westerly air-mass circulation (high zonal index) c. 9500 cal. BP, brought about by high summer insolation and enhanced meridi onal pressure gradients, d18OP at Lake Tibetanus was about 2‰ higher than would be predicted by the modern isotope-temperature relation. The occurrence of long-term changes in d18OP-temperature relations, which are more sensitive measures of palaeoclimate than either d18OP or temperature alone, needs to be taken into account when extracting palaeoclimatic information from continental oxygen-isotope records.
Itraconazole and fluconazole-induced toxicity in rat hepatocytes: a comparativein vitro study
Authors: Somchit N , Hassim S M , Samsudin S H
Published: July 2002

This current study was to investigate the in vitrocytotoxicity of rat hepatocytes induced by the antifungal drugs, itraconazole and fluconazole. Both antifungal drugs caused dose-dependent cytotoxicity. In vitro incubation of hepatocytes with itraconazole revealed significantly higher lactate dehydrogenase (LDH) leakage when compared to fluconazole. Phenobarbital pretreated hepatocytes contained significantly higher total cytochrome P450 content than the control hepatocytes. P450 content was reduced approximately 30% for both types of hepatocytes after 6 hours incubation. Interestingly, cytotoxicity of itraconazole was reduced significantly by phenobarbital pretreatment. Phenobarbital did not have any effect on the cytotoxicity induced by fluconazole. These results demonstrate the in vitro toxicity of hepatocytes induced by itraconazole and fluconazole that were expressed in a dose and time-dependent manner. Phenobarbital plays a role in the cytoprotection of hepatocytes to itraconazole-induced but not fluconazole-induced cytotoxicity in vitro.
Effects of prenatal exposure to combination of acetaminophen, isopropylantipyrine and caffeine on intrauterine development in rats
Authors: Burdan F
Published: July 2002

The common effects of acetaminophen (paracetamol), isopropylantipyrine (propyphenazone) and caffeine on fetal development were examined in rats. The mixture was given in Tween 80 solution once daily, in a constant proportion of 5:3:1, during days 8–14 of gestation in three different doses. Dose S1–3.5 mg/kg acetaminophen, 2.14 mg/kg isopropylantipyrine, 0.7 mg/kg caffeine. Dose S2 was 10 times higher, and S3 100 times higher than dose S1. On day 21 of gestation, the dams were sacrificed and the fetuses were removed. The corpora lutea, resorptions, live and dead fetuses were counted. The pre-and postimplantation mortality were calculated. The weight of fetuses and placentas, and the length of fetuses and their tails were measured. Two-thirds of each litter was processed for Alizarin Red S staining. The remaining third was fixed in Bouin's solution for subsequent visceral examination by using modified Wilson's technique. A significant decrease in body weight in S1 group, and fetal length and placental weight in group S3 were recorded. A significant increase in tail length in group S2 was observed. The number ofcorpora lutea, fetuses, resorptions, preimplantation and postimplantation mortality did not exhibit any significant difference. Nonsignificant incidence of fetal anomalies was found.
A review of ordinal regression models applied on health-related quality of life assessments
Authors: Lall R , Campbell M J , Walters S J , Morgan K ,   MRC CFAS Co-operative
Published: July 2002

There has been increasing emphasis in medical research on the design and analysis of quality of life scales. Many quality of life scales are ordinal and statistical methods such as ordinal regression models have been reviewed on a number of occasions. However, when such models are applied, the way the data have been generated is often overlooked. In this paper we illustrate the use of ordinal regression models, in particular the proportional odds model, the partial proportional odds model and the stereotype model in the MRC Cognitive Function and Ageing Study (MRC CFAS). The partial proportional odds and the stereotype models are often under-utilized, perhaps due to the lack of available software. However, in this paper, analysis based on these models has been carried out using the popular statistical software package SAS and macros devised in SAS. Furthermore, bootstrapping techniques have been applied to obtain valid estimates of the standard errors of the parameters in the stereotype model. Strikingly different results were obtained using the different ordinal regression models. We conclude that the way the data have been generated is particularly important for the analysis of quality of life assessments. Different methods of generating scores yield data with different properties. It is now possible to fit a variety of ordinal regression models and so select the appropriate one that correctly models the data.
Competing risks as a multi-state model
Authors: Andersen Per Kragh , Abildstrom Steen Z , Rosthøj Susanne
Published: July 2002

This paper deals with the competing risks model as a special case of a multi-state model. The properties of the model are reviewed and contrasted to the so-called latent failure time approach. The relation between the competing risks model and right-censoring is discussed and regression analysis of the cumulative incidence function briefly reviewed. Two real data examples are presented and a guide to the practitioner is given.
Questions of Distributive Justice: public health nurses’ perceptions of long-term care insurance for elderly japanese people
Authors: Ellen Barnes Lou , Asahara Kiyomi , Davis Anne J , Konishi Emiko
Published: July 2002

This study examines public health nurses’ perceptions and concerns about the implications of Japan’s new long-term care insurance law concerning care provision for elderly people and their families. Respondents voiced their primary concern about this law as access to services for all elderly people needing care, and defined their major responsibility as strengthening health promotion and illness prevention programmes. Although wanting to expand their roles to meet the health care, social and public policy advocacy needs of elderly persons and their families, respondents also stated their concern for the possible lack of enough resources for this expansion to support family caregivers adequately. They viewed their first function as developing collaborative relationships with local government officials to help to assure sufficient resources to provide the necessary foundation for long-term care programmes to deliver services to all those in need. These concerns fall within the larger ethical issue of distributive justice in a society based on the obligations of the state to citizens and the family to its members, especially elderly relatives, who, according to traditional Japanese values, retain respect.
Ethical Reasoning Observed: a longitudinal study of nursing students
Authors: Nolan Peter W , Markert Doreen
Published: July 2002

All nursing courses in the UK include ethics in the curriculum, although there is considerable variation in the content of ethics courses and the teaching methods used to assist the acquisition of ethical reasoning. The effectiveness of ethics courses continues to be disputed, even when the perceptions and needs of students are taken into account in their design. This longitudinal study, carried out in the UK, but with implications for nurse education in other developed countries, explored the ethical understanding of nursing students and changes in their understanding and approaches to practice over their four years of training (1995-1999). The data collection tools were a questionnaire originally piloted prior to the 1995 study, from which the present study developed, and five vignettes describing ethical dilemmas in health care also piloted in 1995. Students’ thinking progressed as they became more mature as individuals and professionals, although this progress was not necessarily in the direction of greater certainty. Suggestions are made to help nurse educators to maximize the effectiveness of ethics courses in transmitting the skills of ethical reasoning.
Nursing as Vocation
Authors: White Karolyn
Published: July 2002

In this article the author argues that nursing is best understood as a vocational occupation. Using Blum’s model of vocations it is argued that such occupations are socially expressed within practices embodying traditions, norms and a range of meanings: industrial, social, personal and moral. Vocational workers are those who identify in certain ways with these traditions, norms and meanings.

One problem with the vocational model, as it has historically applied to nursing, is that it has been articulated through concepts of motherhood. Nursing was a vocation precisely because the character of the nurse was identified as feminine. The author argues that the vocational model for nursing can be conceptually disentangled from its identification with ideals of motherhood and femininity. It is nursing work and the identification with the moral and social meaning of nursing that give nursing its vocational status, not the feminized character of the nurse.
‘Tender Loving Care’ as a Relational Ethic in Nursing Practice
Authors: Kendrick Kevin David , Robinson Simon
Published: July 2002

In the West, the term ‘tender, loving care’ (TLC) has traditionally been used as a defining term that characterizes nursing. When this expression informs practice, it can comfort the human spirit at times of fear and vulnerability. Such notions offer meaning and resonance to the ‘lived experience’ of giving and receiving care. This suggests that, in a nursing context, TLC is rooted firmly in relationship, that is, the dynamic that exists between carer and cared for.

Despite this emphasis on relationship, there is a scarcity of literature that draws a connection between TLC and the moral challenge that is so much a part of human interaction. In this article we will address this deficit and present a narrative that places TLC at the centre of moral engagement between nurse and patient; in essence, we offer an alternative means of viewing relational ethics.
Being a Good Nurse and Doing the Right Thing: a qualitative study
Authors: Smith Katharine V , Godfrey Nelda S
Published: July 2002

Despite an abundance of theoretical literature on virtue ethics in nursing and health care, very little research has been carried out to support or refute the claims made. One such claim is that ethical nursing is what happens when a good nurse does the right thing. The purpose of this descriptive, qualitative study was therefore to examine nurses’ perceptions of what it means to be a good nurse and to do the right thing. Fifty-three nurses responded to two open-ended questions: (1) a good nurse is one who...; and (2) how does a nurse go about doing the right thing? Three hundred and thirty-one data units were analysed using qualitative content analysis. Seven categories emerged: personal characteristics, professional characteristics, patient centredness, advocacy, competence, critical thinking and patient care. Participants viewed ethical nursing as a complex endeavour in which a variety of decision-making frameworks are used. Consistent with virtue ethics, high value was placed on both intuitive and analytical personal attributes that nurses bring into nursing by virtue of the persons they are. Further investigation is needed to determine just who the ‘good nurse’ is, and the nursing practice and education implications associated with this concept.
The interdisciplinary approach to the treatment of multiple sclerosis patients in Italy: an aspiration or a reality?
Authors: Uccelli M Messmer , Battaglia M A , Zagami P , Solaro C
Published: July 2002

The aim of the study was to assess whether the components necessary for an interdisciplinary approach to the treatment of multiple sclerosis (MS) patients exist in Italian MS clinics and to identify factors that make the difference between reality and aspiration for this type of approach. One hundred two out of 147 neurology departments with MS clinics throughout Italy compiled a questionnaire about characteristics and organizational structure of the clinic, type and number of professionals and resource needs. Eight hundred twenty-three healthcare professionals are currently working in MS clinics: 50% (412) neurologists, 28.7% (236) nurses, 15.1% (124) physical therapists, 3.4% (28) psychologists and 2.8% (23) social workers. Neurologists are evenly distributed between northern and southern parts of the country even though there are nearly double the number of patients followed in northern clinics compared to those in the south. Physicians reported themselves as most in need of continuing education, twice that which the same physicians reported for any other professional. The study has identified issues that contribute to the difficulty in developing and applying an interdisciplinary approach to providing care and services to Italian MS patients. Several factors have been delineated that require significant reshaping in order for this approach to begin to develop.
Stem cell transplantation in multiple sclerosis: multiple choices and multiple challengesy
Authors: Hintzen R Q
Published: July 2002

Multiple sclerosis (MS) is generally considered as an autoimmune disease of the central nervous system. This concept has led to the idea that profound immunosuppression followed by transplantation of stem cell grafts would stop, or at least slow down, disease activity. Supported by the positive effects of hematopoietic stem cell transplantation (HSCT) on experimental autoimmune encephalomyelitis and by anecdotal reports on the beneficial effect of HSCT on MS patients with concomitant malignant disease, HSCT programs for MS have been initiated worldwide. At this stage, it is impossible to draw general conclusions from the preliminary data reported and therefore overenthusiastic expectations should be tempered. The follow-up periods are too short, the groups are too small, the selected patients and protocols too heterogeneous, and publication bias on positive results cannot be excluded. However, there is ample evidence that HSCT is a technically feasible approach in MS, not more dangerous than in the hemato-oncological diseases. For every step in the HSCT procedure, there are many different options. The time has come for a systematic analysis of the safety and efficacy associated with the different methodologies.
Geographies of the unconscious: Robert F. Heizer versus Alfred Kroeber on the drawing of Indian territorial boundaries
Authors: MacCannell Dean
Published: July 2002

This paper revisits a disagreement between two celebrated anthropologists concerning the ways native American groups established their territorial boundaries. A.L. Kroeber suggested that native peoples had fluid limits, with one group’s space blending into neighbouring territories. R.F. Heizer argued differently: that native peoples had clear borders around their territories, lines that unambiguously marked ownership and separated lands. The two different models of marking territory do not fit with what is known about the personalities of Kroeber and Heizer. In his academic and administrative affairs, Kroeber had a highly developed sense of property, propriety, and what constituted ‘crossing the line’. Heizer, on the other hand, was more flexible and liberal. This paper proposes a solution to the puzzle of why the two men adopted theoretical positions against character.
Long-Term Survival and Competing Causes of Death in Patients With Early-Stage Hodgkin’s Disease Treated at Age 50 or Younger
Authors: Ng Andrea K. , Bernardo M. Patricia , Weller Edie , Backstrand Kendall H. , Silver Barbara , Marcus Karen C. , Tarbell Nancy J. , Friedberg Jonathan , Canellos George P. , Mauch Peter M.
Published: July 2002

PURPOSE: To analyze the long-term survival and the pattern and timing of excess mortality in patients with early-stage Hodgkin’s disease.

PATIENTS AND METHODS: Between 1969 and 1997, 1,080 patients age 50 or younger were treated for clinical stage IA to IIB Hodgkin’s disease. Overall survival was determined, and prognostic factors were assessed. Relative risk and absolute excess risk (AR) of mortality were calculated for the entire cohort and by prognostic groups (on the basis of B symptoms, mediastinal status, and number of sites, modified from the European Organization for Research and Treatment of Cancer).

RESULTS: The median follow-up was 12 years. The 15- and 20-year Kaplan-Meier survival estimates were 84% and 78%, respectively. Cox proportional hazards models showed that number of involved sites (P = .006), mediastinal status (P = .02), and histology (P = .02) were independent predictors of death from all causes. The AR of mortality in patients with a favorable prognosis increased over time, whereas for those with an unfavorable prognosis, the AR peaked in the first 5 years, predominantly from Hodgkin’s disease. The relative risk of mortality from all causes, causes other than Hodgkin’s disease, second tumors, and cardiac disease remained significantly elevated more than 20 years after treatment.

CONCLUSION: Patients treated for early-stage Hodgkin’s disease have a sustained excess mortality risk despite good control of the disease. Treatment reduction efforts in patients with early-stage, favorable-prognosis disease should continue, but for patients with an unfavorable prognosis, modified treatment may not be advisable. The excess mortality noted beyond two decades underscores the importance of long-term follow-up care in patients treated for Hodgkin’s disease.
What Can Be Learned From Nonadherent Patients to Promote the Health of Populations?
Authors: Galea Sandro
Published: August 2024

This JAMA Forum discusses patient- and population-level nonadherence to medical advice and elaborates on 4 main categories of reasons that underpin nonadherence.
Electronic Health Record–Based Screening for Intimate Partner Violence
Authors: Lenert Leslie , Rheingold Alyssa A. , Simpson Kit N. , Scherbakov Dmitry , Aiken Michael , Hahn Christine , McCauley Jenna L. , Ennis Naomi , Diaz Vanessa A.
Published: August 2024

Importance

Intimate partner violence (IPV) is a significant public health issue, with a 25% lifetime prevalence. Screening for IPV in primary care is a recommended practice whose effectiveness is debated.

Objective

To assess the effect of an electronic health record (EHR)–based multifactorial intervention screening on the detection of IPV risk in primary care practice.

Design, Setting, and Participants

This cluster randomized clinical trial used a stepped-wedge design to assign 15 family medicine primary care clinics in the Medical University of South Carolina Health System in the Charleston region to 3 matched blocks from October 6, 2020, to March 31, 2023. All women aged 18 to 49 years who were seen in these clinics participated in this study.

Intervention

A noninterruptive EHR alert combined with confidential screening by computer questionnaire using the EHR platform followed by risk assessment and a decision support template.

Main Outcomes and Measures

The main outcomes were the rate at which patients were screened for IPV across the clinics and the rate at which patients at risk for IPV were detected by screening procedures.

Results

The study clinics cared for 8895 unique patients (mean [SD] age, 34.6 [8.7] years; 1270 [14.3%] with Medicaid or Medicare and 7625 [85.7%] with private, military, or other insurance) over the study period eligible for the screening intervention. The intervention had significant effects on the overall rate of screening for IPV, increasing the rate of screening from 45.2% (10 268 of 22 730 patient visits) to 65.3% (22 303 of 34 157 patient visits) when the noninterruptive alert was active (relative risk, 1.46 [95% CI, 1.44-1.49]; P < .001). The confidential screening process was more effective than baseline nurse-led oral screening at identifying patients reporting past-year IPV (130 of 8895 patients [1.5%] vs 9 of 17 433 patients [0.1%]).

Conclusions and Relevance

The intervention was largely effective in increasing screening adherence and the positive detection rate of IPV in primary care. A highly private approach to screening for IPV in primary care may be necessary to achieve adequate detection rates while addressing potential safety issues of patients experiencing IPV.

Trial Registration

ClinicalTrials.gov Identifier: NCT06284148
Visible‐light‐mediated Oxidative Debenzylation of 3‐
O
‐Benzyl‐1,2:5,6‐di‐
O
‐isopropylidene‐α‐D‐glucofuranose
Authors: Madani Amiera , Sletten Eric T. , Cavedon Cristian , Seeberger Peter H. , Pieber Bartholomäus
Published: August 2024

This chapter presents the procedure for the visible‐light‐mediated oxidative debenzylation of 3‐O‐benzyl‐1,2:5,6‐
di‐O‐isopropylidene‐α‐d‐glucofuranose
. Benzyl ethers are important protective groups in the synthesis of carbohydrates due to their excellent stability over a wide range of conditions. However, benzyl ether cleavage requires harsh reduction/oxidation processes, such as catalytic hydrogenolysis, Birch reduction, or oxidation with ozone or BCl, that are hazardous, and poorly functional group tolerant. The photooxidative debenzylation strategy overcomes current limitations of benzyl ethers as protecting groups that arise from the harsh conditions necessary for their cleavage. The methodology enables the use of benzyl ethers as orthogonal protective group that is installed and removed throughout the synthesis of complex molecules and clears the path to the development of new synthetic routes in total synthesis.
Preparation of Pyrylium Tetrafluoroborate (Pyry‐BF
4
)
Authors: Gómez‐Palomino Alejandro , Ghiazza Clément , Busch Julia , Wagner Lucas , Cornella Josep
Published: August 2024

This chapter presents the procedure for the preparation of pyrylium tetrafluoroborate (Pyry‐BF
4
). A facile synthesis of Pyry‐BF
4
is developed to enable the chemoselective activation of aminoheterocycles and sulfonamides, which upon addition of different nucleophiles, permit direct modification of such scaffolds. Capitalizing on the high reactivity of Pyry‐BF
4
with NH
2
groups, a method is developed to enable the activation of the NH
2
groups in aminoheterocycles, to forge the corresponding pyrdinium salts. The use of Pyry‐BF
4
in combination with cheap and available MgCl
2
permits a mild substitution of the NH
2
group in primary sulfonamides to forge the corresponding sulfonyl chloride. Due to the mild conditions of the protocol, sulfonyl fluoride also enables the derivatization of complex sulfonamides as exemplified by the multitude of functional groups tolerated by the protocol.
Preparation of (S)‐3,3′‐Bis(1‐pyrrolidinylmethyl)‐5,5′,6,6′, 7,7′,8,8′‐octahydro‐1,1'‐bi‐2‐naphthol
Authors: Hong Yu , Zhu Yuan‐Yuan , Gu Shuang‐Xi
Published: August 2024

This chapter presents the procedure for the preparation of (S)‐3,3' ‐Bis(1‐pyrrolidinylmethyl) ‐5,5',6,6', 7,7',8,8' ‐octahydro‐1,1' ‐bi‐2‐naphthol. 1,1'‐Bi‐2‐naphthol (BINOL) and its derivatives have been extensively used for asymmetric catalysis and fluorescent recognition of chiral molecules. Derivatives of the partially hydrogenated BINOL, H
8
BINOL, have also been studied and shown improved enantioselectivity over BINOL in many instances. Thus, H
8
BINOL derivatives are interesting ligands for asymmetric catalysis. The title compound, (S)‐1, was synthesized by a concise and facile one‐pot synthetic method. In the new procedure, environment‐friendly ethanol was used as an efficient solvent to replace the previously reported chloroform and dioxane solvents to prepare the H
8
BINOL derivative.
3‐Component Approach to 1,5‐Dihydro‐2
H
‐pyrrol‐2‐one Heterocycles
Authors: Massaro Nicholas P. , Pierce Joshua G.
Published: August 2024

This chapter presents the procedure for the 3‐component approach to 1,5‐Dihydro‐2H‐pyrrol‐2‐one heterocycles. Nitrogen‐containing heterocycles (N‐heterocycles) are a commonality among bioactive natural products often represented in alkaloids and other privileged scaffolds. A frequently observed motif is a 5‐membered N‐heterocycle, present in indoles, pyrroles, pyrrolidines and succinimides. The niche of 5‐membered nitrogen containing heterocyclic natural products has supplied potent anticancer therapies such as vinblastine, as well as treacherous poisons such as strychnine. In summary, N‐heterocycles such as pyrrolidinones have shown to be of significant relevance in the pharmaceutical and fine chemical industry. Furthermore, their extensive presence in natural products makes it of high importance to develop scalable, efficient, and modular approaches to pyrrolidone cores. The procedure described herein provides an attractive means to synthesize highly functionalized pyrrolidinones.
Large Scale Epoxide Opening by a Pendant Silanol
Authors: Thomas Annu Anna , Nagamalla Someshwar , Sathyamoorthi Shyam
Published: August 2024

This chapter presents the procedure for the large scale epoxide opening by a pendant silanol. It focuses on the development of the di‐tert butyl silanol functional group into a synthetically useful auxiliary. Silanols only sporadically appeared in the organic synthesis literature. Silanols are excellent directing groups for Pd‐catalyzed C–H functionalization reaction. A gold‐catalyzed cyclization of silanols is developed onto pendant alkynes; these heterocycles serve as versatile precursors for Mukaiyama‐type aldol condensations. Alkenyl silanols readily cyclize into dioxasilinane organomercury compounds. As epoxides are very versatile and ubiquitous intermediates in organic synthesis, a silanol‐tethered ring opening of epoxides is developed as a first step in this direction.