Bell Correlations and the Common Future

Reichenbach's principle states that in a causal structure, correlations of classical information can stem from a common cause in the common past or a direct influence from one of the events in correlation to the other. The difficulty of explaining Bell correlations through a mechanism in that spirit can be read as questioning either the principle or even its basis: causality. In the former case, the principle can be replaced by its quantum version, accepting as a common cause an entangled state, leaving the phenomenon as mysterious as ever on the classical level (on which, after all, it occurs). If, more radically, the causal structure is questioned in principle, closed space-time curves may become possible that, as is argued in the present note, can give rise to non-local correlations if to-be-correlated pieces of classical information meet in the common future --- which they need to if the correlation is to be detected in the first place. The result is a view resembling Brassard and Raymond-Robichaud's parallel-lives variant of Hermann's and Everett's relative-state formalism, avoiding "multiple realities."Comment: 8 pages, 5 figure

Echium oil is not protective against weight loss in head and neck cancer patients undergoing curative radio(chemo)therapy: a randomised-controlled trial

Background: Therapy-induced mucositis and dysphagia puts head and neck (H&N) cancer patients at increased risk for developing cachexia. Omega-3 fatty acids (n-3 FA) have been suggested to protect against cachexia. We aimed to examine if echium oil, a plant source of n-3 FA, could reduce weight loss in H&N cancer patients undergoing radio(chemo)therapy with curative intent. Methods: In a double-blind trial, patients were randomly assigned to echium oil (intervention (I) group; 7.5 ml bis in die (b.i.d.), 235 mg/ml α-linolenic acid (ALA) + 95 mg/ml stearidonic acid (SDA) + 79 mg/ml γ-linolenic acid (GLA)) or n-3 FA deficient sunflower oil high oleic (control (C) group; 7.5 ml b.i.d.) additional to standard nutritional support during treatment. Differences in percentage weight loss between both groups were analysed according to the intention-to-treat principle. Erythrocyte FA profile, body composition, nutritional status and quality of life were collected. Results: Ninety-one eligible patients were randomised, of whom 83 were evaluable. Dietary supplement adherence was comparable in both groups (median, I: 87%, C: 81%). At week 4, the I group showed significantly increased values of erythrocyte n-3 eicosapentanoic acid (EPA, 14% vs −5%) and n-6 GLA (42% vs −20%) compared to the C group, without a significant change in n-6 arachidonic acid (AA, 2% vs −1%). Intention-to-treat analysis could not reveal a significant reduction in weight loss related to echium oil consumption (median weight loss, I: 8.9%, C: 7.6%). Also, no significant improvement was observed in the other evaluated anthropometric parameters. Conclusions: Echium oil effectively increased erythrocyte EPA and GLA FAs in H&N cancer patients. It failed however to protect against weight loss, or improve nutritional parameters. Trial registration: ClinicalTrials.gov Identifier NCT01596933

Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells

Background: Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into every cell type and to self-renew. These characteristics correlate with a distinct nuclear architecture, epigenetic signatures enriched for active chromatin marks and hyperdynamic binding of structural chromatin proteins. Recently, several chromatin-related proteins have been shown to regulate ESC pluripotency and/or differentiation, yet the role of the major heterochromatin proteins in pluripotency is unknown. Results: Here we identify Heterochromatin Protein 1β (HP1β) as an essential protein for proper differentiation, and, unexpectedly, for the maintenance of pluripotency in ESCs. In pluripotent and differentiated cells HP1β is differentially localized and differentially associated with chromatin. Deletion of HP1β, but not HP1aα, in ESCs provokes a loss of the morphological and proliferative characteristics of embryonic pluripotent cells, reduces expression of pluripotency factors and causes aberrant differentiation. However, in differentiated cells, loss of HP1β has the opposite effect, perturbing maintenance of the differentiation state and facilitating reprogramming to an induced pluripotent state. Microscopy, biochemical fractionation and chromatin immunoprecipitation reveal a diffuse nucleoplasmic distribution, weak association with chromatin and high expression levels for HP1β in ESCs. The minor fraction of HP1β that is chromatin-bound in ESCs is enriched within exons, unlike the situation in differentiated cells, where it binds heterochromatic satellite repeats and chromocenters. Conclusions: We demonstrate an unexpected duality in the role of HP1β: it is essential in ESCs for maintaining pluripotency, while it is required for proper differentiation in differentiated cells. Thus, HP1β function both depends on, and regulates, the pluripotent state

The PINE study: rationale and design of a randomised comparison of epidural injection of local anaesthetics and steroids versus care-as-usual to prevent postherpetic neuralgia in the elderly [ISRCTN32866390]

BACKGROUND: Postherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients. METHODS / DESIGN: The PINE study is an open, multicenter clinical trial in which 550 elderly (age ≥ 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness. CONCLUSION: The PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN

Electronic health records in outpatient clinics: Perspectives of third year medical students

Abstract Background United States academic medical centers are increasingly incorporating electronic health records (EHR) into teaching settings. We report third year medical students' attitudes towards clinical learning using the electronic health record in ambulatory primary care clinics. Methods In academic year 2005&#8211;06, 60 third year students were invited to complete a questionnaire after finishing the required Ambulatory Medicine/Family Medicine clerkship. The authors elicited themes for the questionnaire by asking a focus group of third year students how using the EHR had impacted their learning. Five themes emerged: organization of information, access to online resources, prompts from the EHR, personal performance (charting and presenting), and communication with patients and preceptors. The authors added a sixth theme: impact on student and patient follow-up. The authors created a 21-item questionnaire, based on these themes that used a 5-point Likert scale from "Strongly Agree" to "Strongly Disagree". The authors emailed an electronic survey link to each consenting student immediately following their clerkship experience in Ambulatory Medicine/Family Medicine. Results 33 of 53 consenting students (62%) returned completed questionnaires. Most students liked the EHR's ability to organize information, with 70% of students responding that essential information was easier to find electronically. Only 36% and 33% of students reported accessing online patient information or clinical guidelines more often when using the EHR than when using paper charts. Most students (72%) reported asking more history questions due to EHR prompts, and 39% ordered more clinical preventive services. Most students (69%) reported that the EHR improved their documentation. 39% of students responded that they received more feedback on their EHR notes compared to paper chart notes. Only 64% of students were satisfied with the doctor-patient communication with the EHR, and 48% stated they spent less time looking at the patient. Conclusion Third year medical students reported generally positive attitudes towards using the EHR in the ambulatory setting. They reported receiving more feedback on their electronic charts than on paper charts. However, students reported significant concerns about the potential impact of the EHR on their ability to conduct the doctor-patient encounter.Peer Reviewe

Suffering in long-term cancer survivors: An evaluation of the PRISM-R2 in a population-based cohort

The Pictorial Representation of Illness and Self Measure-Revised 2 (PRISM-R2) has been developed as generic measure to assess suffering. The aim of this study was to evaluate the ability of this instrument to identify long-term cancer survivors with high levels of suffering who may need additional support. 1299 cancer survivors completed the PRISM-R2, the Short Form Health Survey (SF-36), and the Quality of Life-Cancer Survivors questionnaire (QoL-CS). The PRISM-R2 distinguishes between the Self-Illness Separation (SIS) and Illness Perception Measure (IPM), both measuring aspects of suffering. 112 (9%) cancer survivors reported high suffering according to IPM. This group had a higher cancer stage at diagnosis, more cancer recurrences, more comorbidities, and were lower educated compared to people reporting less suffering. The PRISM-R2 could explain substantial amounts of variance (10-14%) in the psychological aspects of the SF-36 and QoL-CS. The IPM also discriminated statistically and clinically significant between high- and low-health status. The PRISM-R2 proved to be able to discriminate between individuals with good and deteriorated levels of QoL. Further evaluation of its validity and screening potential is recommended

Quality of life and salivary output in patients with head-and-neck cancer five years after radiotherapy

BACKGROUND: To describe long-term changes in time of quality of life (QOL) and the relation with parotid salivary output in patients with head-and-neck cancer treated with radiotherapy. METHODS: Forty-four patients completed the EORTC-QLQ-C30(+3) and the EORTC-QLQ-H&N35 questionnaires before treatment, 6 weeks, 6 months, 12 months, and at least 3.5 years after treatment. At the same time points, stimulated bilateral parotid flow rates were measured. RESULTS: There was a deterioration of most QOL items after radiotherapy compared with baseline, with gradual improvement during 5 years follow-up. The specific xerostomia-related items showed improvement in time, but did not return to baseline. Global QOL did not alter significantly in time, although 41% of patients complained of moderate or severe xerostomia at 5 years follow-up. Five years after radiotherapy the mean cumulated parotid flow ratio returned to baseline but 20% of patients had a flow ratio <25%. The change in time of xerostomia was significantly related with the change in flow ratio (p = 0.01). CONCLUSION: Most of the xerostomia-related QOL scores improved in time after radiotherapy without altering the global QOL, which remained high. The recovery of the dry mouth feeling was significantly correlated with the recovery in parotid flow ratio

Computers in the Exam Room: Differences in Physician–Patient Interaction May Be Due to Physician Experience

BACKGROUND: The use of electronic medical records can improve the technical quality of care, but requires a computer in the exam room. This could adversely affect interpersonal aspects of care, particularly when physicians are inexperienced users of exam room computers. OBJECTIVE: To determine whether physician experience modifies the impact of exam room computers on the physician–patient interaction. DESIGN: Cross-sectional surveys of patients and physicians. SETTING AND PARTICIPANTS: One hundred fifty five adults seen for scheduled visits by 11 faculty internists and 12 internal medicine residents in a VA primary care clinic. MEASUREMENTS: Physician and patient assessment of the effect of the computer on the clinical encounter. MAIN RESULTS: Patients seeing residents, compared to those seeing faculty, were more likely to agree that the computer adversely affected the amount of time the physician spent talking to (34% vs 15%, P = 0.01), looking at (45% vs 24%, P = 0.02), and examining them (32% vs 13%, P = 0.009). Moreover, they were more likely to agree that the computer made the visit feel less personal (20% vs 5%, P = 0.017). Few patients thought the computer interfered with their relationship with their physicians (8% vs 8%). Residents were more likely than faculty to report these same adverse effects, but these differences were smaller and not statistically significant. CONCLUSION: Patients seen by residents more often agreed that exam room computers decreased the amount of interpersonal contact. More research is needed to elucidate key tasks and behaviors that facilitate doctor–patient communication in such a setting

Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients

Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients

UVB phototherapy in an outpatient setting or at home: a pragmatic randomised single-blind trial designed to settle the discussion. The PLUTO study

BACKGROUND: Home ultraviolet B (UVB) treatment is a much-debated treatment, especially with regard to effectiveness, safety and side effects. However, it is increasingly being prescribed, especially in the Netherlands. Despite ongoing discussions, no randomised research has been performed, and only two studies actually compare two groups of patients. Thus, firm evidence to support or discourage the use of home UVB phototherapy has not yet been obtained. This is the goal of the present study, the PLUTO study (Dutch acronym for "national trial on home UVB phototherapy for psoriasis"). METHODS: We designed a pragmatic randomised single-blind multi-centre trial. This trial is designed to evaluate the impact of home UVB treatment versus UVB phototherapy in a hospital outpatient clinic as to effectiveness, quality of life and cost-effectiveness. In total 196 patients with psoriasis who were clinically eligible for UVB phototherapy were included. Normally 85% of the patients treated with UVB show a relevant clinical response. With a power of 80% and a 0.05 significance level it will be possible to detect a reduction in effectiveness of 15%. Effectiveness will be determined by calculating differences in the Psoriasis Area and Severity Index (PASI) and the Self Administered PASI (SAPASI) scores. Quality of life is measured using several validated generic questionnaires and a disease-specific questionnaire. Other outcome measures include costs, side effects, dosimetry, concomitant use of medication and patient satisfaction. Patients are followed throughout the therapy and for 12 months thereafter. The study is no longer recruiting patients, and is expected to report in 2006. DISCUSSION: In the field of home UVB phototherapy this trial is the first randomised parallel group study. As such, this trial addresses the weaknesses encountered in previous studies. The pragmatic design ensures that the results can be well generalised to the target population. Because, in addition to effectiveness, aspects such as quality of life and cost-effectiveness are also taken into consideration, this study will produce valuable evidence to either support or discourage prescription of home UVB phototherapy. TRIAL REGISTRATION: Current controlled trials/Nederlands Trial register: ISRCTN83025173. Clinicaltrials.gov: NCT0015093