A Recursive Partitioning Analysis Demonstrating Risk Subsets for 8-Year Biochemical Relapse After Margin-Positive Radical Prostatectomy Without Adjuvant Hormone or Radiation Therapy.

PURPOSE: The cohort of patients with locally advanced prostate cancer (PC) and positive surgical margin(s) at radical prostatectomy (RP) who would benefit from salvage or adjuvant treatment is unclear. This study examines the risk of prostate-specific antigen (PSA) relapse in a large population of men with PC after margin-positive RP. METHODS AND MATERIALS: Using a multi-institutional database, patients with clinically localized PC who underwent RP between 2002 and 2010 with recorded follow-up PSA were retrospectively selected. Patients were excluded for pathologic seminal vesicle or lymph node involvement, metastatic disease, pre-RP PSA ≥ 30, or adjuvant (nonsalvage) radiation therapy or hormone therapy. The primary endpoint was biochemical relapse free survival (bRFS), where PSA failure was defined as PSA > 0.10 ng/mL and rising, or at salvage intervention. The Kaplan-Meier method was employed for bRFS estimates; recursive partitioning analysis using cumulative or single maximal margin extent (ME) and Gleason grade (GG) at RP was applied to identify variables associated with bRFS. RESULTS: At median follow-up of 105 months, 210 patients with positive margins at RP were eligible for analysis, and 89 had experienced PSA relapse. Median age was 61 years (range, 43-76), and median pre-RP PSA 5.8 ng/mL (1.6-26.0). Recursive partitioning analysis yielded 5 discrete risk groups, with the lowest risk group (GG1, ≤ 2 mm ME) demonstrating a bRFS of 92% at 8 years compared with the highest risk group (GG3-5, ≥ 3 mm ME) of 11%. CONCLUSIONS: This retrospective study suggests that it may be possible to risk-stratify patients undergoing margin-positive RP using commonly acquired clinical and pathologic variables. Patients with low-grade tumors and minimally involved margins have a very low recurrence risk and may be able to forego postprostatectomy radiation. Meanwhile, those with higher grade and greater involvement could benefit from adjuvant or early salvage radiation therapy.

Does Attention Increase the Value of Choice Alternatives?

A growing recognition of the role of attention in decision-making has been driven by both the technology of eye tracking and the development of models that explicitly incorporate attention. One result of this convergence is the arresting claim that attention, by itself, can increase the perceived value of a decision alternative. In this review, we cover the origins of that claim, its empirical foundation, and the reasoning that supports it. The conclusion is that, to date, there is not sufficient evidence to support the claim. Alternative explanations for the extant evidentiary base are discussed, as is the balance between the bottom-up influence of empirical evidence and the top-down commitment to a conceptual framework.

Long-term outcome comparison for standard fractionation (>59 Gy) versus hyperfractionated (>45 Gy) radiotherapy plus concurrent chemotherapy for limited-stage small-cell lung cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is commonly employed in limited-stage small-cell lung cancer (LS-SCLC); however, the optimal radiotherapy regimen is still unknown. This 3-institution analysis compares long-term disease control and survival outcomes for once- (QD) versus twice-daily (BID) radiotherapy at contemporary doses. METHODS AND MATERIALS: Data were collected for LS-SCLC patients treated with platinum-based CCRT and planned RT doses of >5940 cGy at >180 cGy QD or >4500 cGy at 150 cGy BID. Comparative outcome analyses were performed for treatment groups. RESULTS: From 2005 through 2014, 132 patients met inclusion criteria for analysis (80 QD, 52 BID). Treatment groups were well-balanced, excepting higher rate of advanced mediastinal staging, longer interval from biopsy to treatment initiation, and lower rate of prophylactic cranial irradiation for the QD group, as well as institutional practice variation. At median survivor follow-up of 33.5 months (range, 4.6-105.8), 80 patients experienced disease failure (44 QD, 36 BID), and 106 died (62 QD, 44 BID). No differences in disease control or survival were demonstrated between treatment groups. CONCLUSION: The present analysis did not detect a difference in disease control or survival outcomes for contemporary dose QD versus BID CCRT in LS-SCLC.

Antibiotic Delivery Strategies to Treat Skin Infections When Innate Antimicrobial Defense Fails.

The epidermal skin barrier protects the body from a host of daily challenges, providing protection against mechanical insults and the absorption of chemicals and xenobiotics. In addition to the physical barrier, the epidermis also presents an innate defense against microbial overgrowth. This is achieved through the presence of a diverse collection of microorganisms on the skin (the "microbiota") that maintain a delicate balance with the host and play a significant role in overall human health. When the skin is wounded, the local tissue with a compromised barrier can become colonized and ultimately infected if bacterial growth overcomes the host response. Wound infections present an immense burden in healthcare costs and decreased quality of life for patients, and treatment becomes increasingly important because of the negative impact that infection has on slowing the rate of wound healing. In this review, we discuss specific challenges of treating wound infections and the advances in drug delivery platforms and formulations that are under development to improve topical delivery of antimicrobial treatments.

An In Vitro Model of Triple-Negative Breast Cancer.

We have characterized two highly tumorigenic and metastatic basal B TNBC cell lines, XtMCF and LmMCF, with the additional values of having the normal and early-stage counterparts of them. This model allows the study of the evolution of TNBC, and investigates molecular pathways at different stages of transformation and progression in a relatively constant genetic background. This constitutes an ideal model for developing targeted therapy in two important fields in cancer biology which are the epithelial mesenchymal transition (EMT) and cancer stem cells (CSC).

Is More Always Better? An Assessment of the Impact of Lymph Node Yield on Outcome for Clinically Localized Prostate Cancer with Low/Intermediate Risk Pathology (pT2-3a/pN0) Managed with Prostatectomy Alone.

The clinical impact of lymph node dissection extent remains undetermined in the contemporary setting, as reflected in care pattern variations. Despite some series demonstrating a direct relationship between number of lymph nodes identified and detection of nodal involvement, the correlation between lymph node yield and disease control or survival outcomes remains unclear. Patients with clinically localized prostate cancer, pre-RP PSA <30, and pT2-3a/N0 disease at RP were retrospectively identified from two databases for inclusion. Those who received pre- or post-RP radiotherapy or hormone therapy were excluded. Kaplan-Meier method was employed for survival probability estimation. Cox regression models were used to assess bRFS differences between subsets. From 2002 to 2010, 667 eligible patients were identified. The median age was 61 yrs. (range, 43-76), with median PSA 5.6 ng/dL (0.9-28.0). At RP, most patients had pT2c (64%) disease with Gleason Score (GS) ≤6 (43%) or 7 (48%); 218 (33%) patients had positive margins (M+). At median clinical and PSA follow-up of 96 and 87 months, respectively, 146 patients (22%) experienced PSA failure with an estimated bRFS of 81%/76% at 5/8 years. For patients who underwent LND, univariable analysis identified PSA (at diagnosis), higher GS (≥7, at biopsy or RP), intermediate/high risk stratification, M+ as adversely associated with bRFS (all p < 0.01). A higher number of LNs excised was not associated with improved bRFS for the entire cohort (HR = 0.97, p = 0.27), nor for any clinical risk stratum, biopsy GS, or RP GS subgroup. This study did not demonstrate an association between LN yield and bRFS in patients with clinically localized pT2-3a/pN0 prostate cancer managed with RP alone, either in the entire population or with substratification by clinical risk stratum or GS.

Bayesian Revision vs. Information Distortion.

The rational status of the Bayesian calculus for revising likelihoods is compromised by the common but still unfamiliar phenomenon of information distortion. This bias is the distortion in the evaluation of a new datum toward favoring the currently preferred option in a decision or judgment. While the Bayesian calculus requires the independent combination of the prior probability and a new datum, information distortion invalidates such independence (because the prior influences the datum). Although widespread, information distortion has not generally been recognized. First, individuals are not aware when they themselves commit this bias. In addition, it is often hidden in more obvious suboptimal phenomena. Finally, the Bayesian calculus is usually explained only with undistortable data like colored balls drawn randomly. Partly because information distortion is unrecognized by the individuals exhibiting it, no way has been devised for eliminating it. Partial reduction is possible in some situations such as presenting all data simultaneously rather than sequentially with revision after each datum. The potential dangers of information distortion are illustrated for three professional revision tasks: forecasting, predicting consumer choices from internet data, and statistical inference from experimental results. The optimality of the Bayesian calculus competes with people's natural desire that their belief systems remain coherent in the face of new data. Information distortion provides this coherence by biasing those data toward greater agreement with the currently preferred position-but at the cost of Bayesian optimality.

Photoallergic Contact Dermatitis to Sunscreens Containing Oxybenzone in La Plata, Argentina. / Dermatitis por contacto fotoalérgica a protectores solares con oxibenzona en La Plata, Argentina.

BACKGROUND: Photoallergic contact dermatitis (PACD) to oxybenzone was reported for the first time in 1980. Oxybenzone is the most common photoallergen in the United States and Canada and the fourth most common .in Europe. There are no studies or data on the prevalence of oxybenzone PACD in Argentina. OBJECTIVE: To determine the proportion of photosensitive patients with PACD to oxybenzone. METHODS: We conducted a descriptive cross-sectional study of 35 patients with photosensitivity reactions confirmed by photopatch testing at the Research Center of Hospital Público San Martín in La Plata, Argentina, in 2015 and 2016. RESULTS: PACD was identified in 6 patients (17.14%). Five of these (14.28%) had at least one positive reaction to oxybenzone in the photopatch test; 4 had a reaction at irradiated sites only (5 J/cm2 UVA) and one had a reaction at both irradiated and nonirradiated sites. CONCLUSIONS: PACD to sunscreens containing oxybenzone is common and is probably underdiagnosed due to a lack of confirmation by photopatch tests or other diagnostic tools. Sensitization rates vary according to region and are influenced by sunscreen ingredients and variations in the use of sunscreen products, cosmetics, and topical drugs.

Gleason Score ≤ 6 Prostate Cancer at Radical Prostatectomy: Does a High-Risk Setting Truly Exist? A Recursive Partitioning Analysis.

BACKGROUND: The purpose of this study was to determine whether a "high-risk" subpopulation of low-grade (Gleason score ≤6) prostate cancer defined by lower prostate-specific antigen (PSA) relapse-free survival (bRFS) might be identified within a large population of men who underwent radical prostatectomy (RP) alone, with mature follow-up. PATIENTS AND METHODS: Patients were retrospectively identified for inclusion by cT1-2 prostate cancer managed with RP alone. Exclusion criteria were: Gleason score ≥7 at RP, any pre- or post-RP radiotherapy or hormone therapy, or PSA follow-up <12 months. The Kaplan-Meier method was used for survival estimates; recursive partitioning by conditional inference analysis was applied to identify variables associated with bRFS. RESULTS: From 2002 through 2010, 284 eligible patients were identified. Median age was 60 years (range, 44-76 years), 233 (82%) were cT1c, and median PSA was 5.3 ng/dL (92% ≤10). The median biopsy to RP interval was 50 days (range, 11-410, with 97% <180 days). Eighty patients (28%) had positive margin (M+). At a median follow-up of 92.6 months (range, 16.9-160.9, with 45% followed ≥ 8 years), 32 patients (11%) had PSA failure, with an estimated 8-year bRFS rate of 89%. In univariate analysis, M+, extraprostatic extension, detectable initial post-RP PSA, and longer biopsy to RP interval were significantly associated with lower bRFS. M+ and longer biopsy to RP interval remained significant in multivariable analysis. Recursive partitioning analysis identified M+ as the only stratification factor, with 8-year bRFS estimates of 74% versus 95% for M+ versus margin-negative. CONCLUSION: Gleason score ≤6 prostate cancer managed using RP alone is associated with high rates of bRFS; however, margin positivity predicts early PSA failure rates in >20% of patients.

Rapamycin inhibits mTOR/p70S6K activation in CA3 region of the hippocampus of the rat and impairs long term memory.

The present study was aimed at establishing whether the mTOR pathway and its downstream effector p70S6K in CA3 pyramidal neurons are under the modulation of the cholinergic input to trigger the formation of long term memories, similar to what we demonstrated in CA1 hippocampus. We performed in vivo behavioral experiments using the step down inhibitory avoidance test in adult Wistar rats to evaluate memory formation under different conditions. We examined the effects of rapamycin, an inhibitor of mTORC1 formation, scopolamine, a muscarinic receptor antagonist or mecamylamine, a nicotinic receptor antagonist, on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition was conducted 30min after i.c.v. injection of rapamycin. Recall testing was performed 1h, 4h or 24h after acquisition. We found that (1) mTOR and p70S6K activation in CA3 pyramidal neurons were involved in long term memory formation; (2) rapamycin significantly inhibited mTOR and of p70S6K activation at 4h, and long term memory impairment 24h after acquisition; (3) scopolamine impaired short but not long term memory, with an early increase of mTOR/p70S6K activation at 1h followed by stabilization at longer times; (4) mecamylamine and scopolamine co-administration impaired short term memory at 1h and 4h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1h and 4h; (5) mecamylamine and scopolamine treatment did not impair long term memory formation; (6) unexpectedly, rapamycin increased mTORC2 activation in microglial cells. Our results demonstrate that in CA3 pyramidal neurons the mTOR/p70S6K pathway is under the modulation of the cholinergic system and is involved in long-term memory encoding, and are consistent with the hypothesis that the CA3 region of the hippocampus is involved in memory mechanisms based on rapid, one-trial object-place learning and recall. Furthermore, our results are in accordance with previous reports that selective molecular mechanisms underlie either short term memory, long term memory, or both. Furthermore, our discovery that administration of rapamycin increased the activation of mTORC2 in microglial cells supports a reappraisal of the beneficial/adverse effects of rapamycin administration.

Prospective, comparative effectiveness trial of cow's milk elimination and swallowed fluticasone for pediatric eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease in which food antigens play a key role. Current therapeutic options are limited to long-term steroid medication and dietary elimination of multiple foods, each of which is challenging. Our objective was to compare single food elimination of cow's milk to swallowed fluticasone in pediatric EoE patients. This is a prospective, comparative effectiveness trial of newly diagnosed EoE patients (ages 2-18 years) treated with swallowed fluticasone (n = 24) or elimination of cow's milk (n = 20). The dual outcome measures of repeat esophageal biopsy (6-8 weeks) and change in Pediatric Quality of Life Inventor (PedsQL) EoE Module and Symptoms Scales were used to assess response to treatment. After 6-8 weeks of treatment, peak esophageal eosinophil counts decreased to below the threshold of 15 eosinophils/high-power field in 64% of patients treated with cow's milk elimination and 80% of patients treated with swallowed fluticasone (P = 0.4). Mean PedsQL EoE Module total scores (69 vs. 82; P < 0.005) and Total Symptoms scores (58 vs. 75; P = 0.001) showed significant improvement with cow's milk elimination. Among children treated with swallowed fluticasone, mean PedsQL EoE Module total scores (64 vs. 75; P < 0.05) and Total Symptoms scores (58 vs. 69; P < 0.01) were also significantly improved after 6-8 weeks of therapy. Removal of cow's milk from the diet is an effective single food elimination treatment for pediatric patients with EoE as assessed by statistically significant histologic and symptomatic improvement. Cow's milk elimination may be more desirable for EoE patients who do not want to take chronic, long-term steroid medications.

A trabecular plate-like phenotype is overrepresented in Chinese-American versus Caucasian women.

UNLABELLED: This study used extreme phenotype selection to define two trabecular bone phenotypes in a cohort of Chinese-American and Caucasian women. A trabecular plate-predominant phenotype is more common in Chinese-Americans while the rod-predominant phenotype is more typical of Caucasians. The robustness of these phenotypic associations with respect to lifestyle factors suggests that this trait may have a genetic basis and that these phenotypes can be utilized in future genetic studies. INTRODUCTION: Compared to Caucasians, Chinese-Americans have more plate-like trabecular bone when measured by individual trabecula segmentation (ITS). These findings suggest a phenotypic difference between the races, which may be amenable to genetic analysis. We sought to identify a single ITS plate trait to pursue in genetic studies by conducting an extreme phenotype selection strategy to numerically define two distinct phenotypes-plate-like and rod-like-and determine whether the selected phenotypic associations were independent of lifestyle factors in order to conduct future genetic studies. METHODS: A previously described cohort of 146 Chinese-American and Caucasian women with high-resolution peripheral quantitative computed tomography imaging and ITS analyses were studied with logistic regression and receiver operator characteristic analyses. RESULTS: The tibial plate-to-rod (TPR) ratio was the best ITS discriminator of race. Using extreme phenotypic selection, two TPR ratio phenotypes were defined numerically: plate-like as a TPR ratio value in the highest quartile (≥1.336) and rod-like as a TPR ratio value in the lowest quartile (≤0.621). Women with a plate-like phenotype were 25.7 times more likely (95 % CI 7.3-90.1) to be Chinese-American than women with rod-like morphology. After controlling for constitutional and lifestyle covariates, women in the highest vs. lowest TPR ratio quartile were 85.0 times more likely (95 % CI 12.7-568.0) to be Chinese-American. CONCLUSION: Using extreme phenotype selection, we defined a plate- and rod-like trabecular bone phenotype for the TPR ratio trait. The former phenotype is more common in Chinese-American women, while the latter is more typical of Caucasian women. The robustness of these phenotypic associations after controlling for differences in constitution and lifestyle suggest that the TPR ratio may have a genetic basis and that the extreme phenotypes defined in this analysis can be utilized for future studies.

Progressive increase of glucose transporter-3 (GLUT-3) expression in estrogen-induced breast carcinogenesis

INTRODUCTION: Increased glucose uptake and glycolysis are main metabolic characteristics of malignant cells. A family of glucose transporters (GLUTs) facilitates glucose movement across the plasma membranes in a tumor-specific manner. Glucose transporter-1 (GLUT-1), GLUT-3 and recently GLUT-12, have been previously shown in breast cancer cells and are found to be associated with poor prognosis. In addition, it has been shown that estrogen plays critical roles in GLUT regulation, however, the stage-specific GLUT regulation of mammary carcinogenesis is unclear. METHODS: GLUT expression patterns were investigated in an in vitro-in vivo progressive, estrogen-induced, mammary carcinogenesis model which consisted of four cell lines, with same genetic background. In this model, different stages of tumor initiation and progression are represented, MCF-10F being the normal stage, E2 cells the transformed stage by estrogen, C5 cells, the invasive stage, and T4 cells the tumorigenic stage. In addition, loss of ductulogenesis and solid mass formation in collagen matrix and invasiveness of the cells were counted. RESULTS: Real time PCR showed that GLUT1 expression was downregulated in MCF10F after treatment with 17β-estradiol (E2), and in the invasive cell type (C5), but not in the tumor cells (T4), which had no changes compared to MCF10F. C5 and T4 cells showed the highest rate of GLUT-3 expression. These cells were also found to be associated with loss of ductulogenesis, solid mass formation and higher invasive capacity, whereas, GLUT-12 was downregulated in C5 and T4 cells. CONCLUSION: Estrogen-induced malignant transformation is associated with remarkable and progressive GLUT-3 expression, GLUT-1 re-expression at further stages, as well as GLUT-12 downregulation (AU)

Progressive increase of glucose transporter-3 (GLUT-3) expression in estrogen-induced breast carcinogenesis.

INTRODUCTION: Increased glucose uptake and glycolysis are main metabolic characteristics of malignant cells. A family of glucose transporters (GLUTs) facilitates glucose movement across the plasma membranes in a tumor-specific manner. Glucose transporter-1 (GLUT-1), GLUT-3 and recently GLUT-12, have been previously shown in breast cancer cells and are found to be associated with poor prognosis. In addition, it has been shown that estrogen plays critical roles in GLUT regulation, however, the stage-specific GLUT regulation of mammary carcinogenesis is unclear. METHODS: GLUT expression patterns were investigated in an in vitro-in vivo progressive, estrogen-induced, mammary carcinogenesis model which consisted of four cell lines, with same genetic background. In this model, different stages of tumor initiation and progression are represented, MCF-10F being the normal stage, E2 cells the transformed stage by estrogen, C5 cells, the invasive stage, and T4 cells the tumorigenic stage. In addition, loss of ductulogenesis and solid mass formation in collagen matrix and invasiveness of the cells were counted. RESULTS: Real time PCR showed that GLUT1 expression was downregulated in MCF10F after treatment with 17ß-estradiol (E2), and in the invasive cell type (C5), but not in the tumor cells (T4), which had no changes compared to MCF10F. C5 and T4 cells showed the highest rate of GLUT-3 expression. These cells were also found to be associated with loss of ductulogenesis, solid mass formation and higher invasive capacity, whereas, GLUT-12 was downregulated in C5 and T4 cells. CONCLUSION: Estrogen-induced malignant transformation is associated with remarkable and progressive GLUT-3 expression, GLUT-1 re-expression at further stages, as well as GLUT-12 downregulation.

Development of the ITHACA Toolkit for monitoring human rights and general health care in psychiatric and social care institutions.

Background. Human rights violations are commonly experienced by people in psychiatric and social care institutions. States and private organizations providing such health and social services must comply with international human rights law. Monitoring of such compliance is increasingly recognized as a vital component in ensuring that rights are respected and violations are brought out in the open, remedied and prevented. Aims. The Institutional Treatment, Human Rights and Care Assessment (ITHACA) project produced a method to document violations and good practice with the aim of preventing human rights violations and improving general health care practice in psychiatric and social care institutions (www.ithacastudy.eu). Methods. A methodological and implementation study conducted across 15 European countries developed and assessed the ITHACA Toolkit in monitoring visits to 87 mental health organizations. Results. The toolkit is available in 13 European languages and has demonstrated applicability in a range of contexts and conditions. The information gathered through monitoring visits can document both good practice and areas for improvement. Conclusions. The ITHACA Toolkit is an acceptable and feasible method for the systematic monitoring of human rights and general health care in psychiatric and social care institutions that explicitly calls for the participation of service users in the monitoring of human rights violations and general health care practice.

Synchronous bilateral inverted papilloma of the temporal bone: Case report and review of the literature.

BACKGROUND: Temporal bone inverted papilloma (IP) is an extremely rare tumor. Its etiology is unknown and represents a source of debate. Only 2 previous cases of bilateral temporal bone IP have been reported. A case report and review of the literature via PubMed database search are presented. MATHODS AND RESULTS: A 52-year-old African-American man who initially underwent medial maxillectomy for right-sided nasal IP returned with bilateral temporal bone IP 7 months later without evidence of extension through the Eustachian tubes. Despite multiple resections and adjuvant radiation, the tumor transformed into squamous cell carcinoma and progressed to involve the intracranial dura, temporal lobe, and cervical dura. CONCLUSIONS: Multiple origins may exist for temporal IP: direct extension, iatrogenic seeding, or development from ectopic Schneiderian epithelium. Temporal bone IP appears to represent a much more aggressive tumor than its nasal counterpart, necessitating aggressive early surgical intervention to decrease recurrence and transformation risk.

Definitive chemoradiotherapy for esophageal carcinoma.

Radiation therapy plays an important role in the treatment of esophageal cancer. Radiation therapy may be combined with chemotherapy, used as a component of induction therapy, used in the adjuvant setting, or used for palliation of advanced disease. Chemotherapy is also occasionally used as a solitary treatment modality for patients with esophageal cancer. Current treatment protocols include multiple agents, and agents directed against specific molecular targets have been investigated in clinical trials. This article discusses future directions related to the selection of radiation treatment protocols, novel targeted chemotherapeutic agents, and the selection of patients for surgery.

Information distortion in physicians' diagnostic judgments.

BACKGROUND: Information distortion suggests that people change the evaluation of new information to support an emerging belief. The present study was designed to measure the extent to which physicians distort incoming medical information to support an emerging diagnosis. DESIGN: Data were collected via an anonymous questionnaire. The experimental group (102 physicians) read 3 patient scenarios, each with 2 competing diagnoses. Physicians first read information that favored 1 of the 2 diagnoses (the "steer"). They then rated a series of neutral cues that favored neither diagnosis. At each cue presentation, respondents rated the extent to which cues favored either diagnosis and updated the strength of their diagnostic belief. After the neutral cues in the third scenario, respondents rated cues that opposed the initial steer. A control group (36 physicians) rated all the cues in random order and not within scenarios, thus providing unbiased baseline ratings for calculating distortion in the experimental group. RESULTS: Distortion was statistically significant (P < 0.001) and was associated with the strength of belief in the leading diagnosis. Physicians with over 10 years in practice distorted less than their less experienced counterparts ( $$\overline{X}$$ = 1.04 v. $$\overline{X}$$ = 1.78, P < 0.05). Having developed an initial diagnostic leaning consistent with the steer, 56% of physicians remained committed to it after receiving the conflicting cues. Distortion was strongly associated with commitment to the steer (odds ratio, 1.4; 95% confidence interval, 1.03-1.79; P = 0.03). LIMITATIONS: Physicians did not elicit information; therefore, the authors cannot estimate the size of distortion in tasks involving information search. CONCLUSIONS: Distortion could partly explain commitment of physicians to an early diagnosis. Both distortion and strength of initial diagnostic belief seem to decline after 10 years in family medicine.

Re-entrant phase behaviour of network fluids: a patchy particle model with temperature-dependent valence.

We study a model consisting of particles with dissimilar bonding sites ("patches"), which exhibits self-assembly into chains connected by Y-junctions, and investigate its phase behaviour by both simulations and theory. We show that, as the energy cost ε(j) of forming Y-junctions increases, the extent of the liquid-vapour coexistence region at lower temperatures and densities is reduced. The phase diagram thus acquires a characteristic "pinched" shape in which the liquid branch density decreases as the temperature is lowered. To our knowledge, this is the first model in which the predicted topological phase transition between a fluid composed of short chains and a fluid rich in Y-junctions is actually observed. Above a certain threshold for ε(j), condensation ceases to exist because the entropy gain of forming Y-junctions can no longer offset their energy cost. We also show that the properties of these phase diagrams can be understood in terms of a temperature-dependent effective valence of the patchy particles.

Reentrant phase diagram of network fluids.

We introduce a microscopic model for particles with dissimilar patches which displays an unconventional "pinched" phase diagram, similar to the one predicted by Tlusty and Safran in the context of dipolar fluids [Science 290, 1328 (2000)]. The model-based on two types of patch interactions, which account, respectively, for chaining and branching of the self-assembled networks-is studied both numerically via Monte Carlo simulations and theoretically via first-order perturbation theory. The dense phase is rich in junctions, while the less-dense phase is rich in chain ends. The model provides a reference system for a deep understanding of the competition between condensation and self-assembly into equilibrium-polymer chains.