Dosimetric validation of a magnetic resonance image gated radiotherapy system using a motion phantom and radiochromic film.

PurposeMagnetic resonance image (MRI) guided radiotherapy enables gating directly on the target position. We present an evaluation of an MRI-guided radiotherapy system's gating performance using an MRI-compatible respiratory motion phantom and radiochromic film. Our evaluation is geared toward validation of our institution's clinical gating protocol which involves planning to a target volume formed by expanding 5 mm about the gross tumor volume (GTV) and gating based on a 3 mm window about the GTV.MethodsThe motion phantom consisted of a target rod containing high-contrast target inserts which moved in the superior-inferior direction inside a body structure containing background contrast material. The target rod was equipped with a radiochromic film insert. Treatment plans were generated for a 3 cm diameter spherical planning target volume, and delivered to the phantom at rest and in motion with and without gating. Both sinusoidal trajectories and tumor trajectories measured during MRI-guided treatments were used. Similarity of the gated dose distribution to the planned, motion-frozen, distribution was quantified using the gamma technique.ResultsWithout gating, gamma pass rates using 4%/3 mm criteria were 22-59% depending on motion trajectory. Using our clinical standard of repeated breath holds and a gating window of 3 mm with 10% target allowed outside the gating boundary, the gamma pass rate was 97.8% with 3%/3 mm gamma criteria. Using a 3 mm window and 10% allowed excursion, all of the patient tumor motion trajectories at actual speed resulting in at least 95% gamma pass rate at 4%/3 mm.ConclusionsOur results suggest that the device can be used to compensate respiratory motion using a 3 mm gating margin and 10% allowed excursion results in conjunction with repeated breath holds. Full clinical validation requires a comprehensive evaluation of tracking performance in actual patient images, outside the scope of this study

Case report: West-Nile virus infection in two Dutch travellers returning from Israel

We report about West Nile virus (WNV) infections in a symptomatic traveller returning from Israel and in her asymptomatic travel companion. Knowledge of the current epidemiological situation in Israel from where WNV cases were reported recently enabled a rapid diagnosis. The described cases serve as a reminder for physicians to consider WNV in the diagnosis of patients returning from areas with potential circulation of the virus

High Discordance of Chest X-ray and CT for Detection of Pulmonary Opacities in ED Patients: Implications for Diagnosing Pneumonia

Objective To evaluate the diagnostic performance of chest x-ray (CXR) compared to computed tomography (CT) for detection of pulmonary opacities in adult emergency department (ED) patients. Methods We conducted an observational cross-sectional study of adult patients presenting to 12 EDs in the United States from July 1, 2003, through November 30, 2006, who underwent both CXR and chest CT for routine clinical care. CXRs and CT scans performed on the same patient were matched. CXRs and CT scans were interpreted by attending radiologists and classified as containing pulmonary opacities if the final radiologist report noted opacity, infiltrate, consolidation, pneumonia, or bronchopneumonia. Using CT as a criterion standard, the diagnostic test characteristics of CXR to detect pulmonary opacities were calculated. Results The study cohort included 3423 patients. Shortness of breath, chest pain and cough were the most common complaints, with 96.1% of subjects reporting at least one of these symptoms. Pulmonary opacities were visualized on 309 (9.0%) CXRs and 191 (5.6 %) CT scans. CXR test characteristics for detection of pulmonary opacities included: sensitivity 43.5% (95% CI, 36.4%-50.8%); specificity 93.0% (95% CI, 92.1%-93.9%); positive predictive value 26.9% (95% CI, 22.1%-32.2%); and negative predictive value 96.5% (95% CI, 95.8%-97.1%). Conclusion In this multicenter cohort of adult ED patients with acute cardiopulmonary symptoms, CXR demonstrated poor sensitivity and positive predictive value for detecting pulmonary opacities. Reliance on CXR to identify pneumonia may lead to significant rates of misdiagnosis

Some Siegel modular standard L-values, and Shafarevich–Tate groups

AbstractWe explain how the Bloch–Kato conjecture leads us to the following conclusion: a large prime dividing a critical value of the L-function of a classical Hecke eigenform f of level 1, should often also divide certain ratios of critical values for the standard L-function of a related genus two (and in general vector-valued) Hecke eigenform F. The relation between f and F (Harderʼs conjecture in the vector-valued case) is a congruence involving Hecke eigenvalues, modulo the large prime. In the scalar-valued case we prove the divisibility, subject to weak conditions. In two instances in the vector-valued case, we confirm the divisibility using elaborate computations involving special differential operators. These computations do not depend for their validity on any unproved conjecture

T helper cell subsets specific for pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis

Background: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. Methods: Peripheral blood human memory CD4+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. Results: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. Conclusions: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions

Ethnicity and baseline symptomatology in patients with an At Risk Mental State for psychosis

Ethnicity has been associated with different incidence rates and different symptom profiles in young patients with psychotic-like disorders. No studies so far have examined the effect of ethnicity on symptoms in people with an At Risk Mental State (ARMS). In this cross-sectional study, we analysed the relationship between ethnicity and baseline data on the severity of psychopathology scores in 201 help-seeking patients who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. Eighty-seven of these patients had a non-Dutch ethnicity. We explored the possible mediating role of ethnic identity. Higher rates of negative symptoms, and of anhedonia in particular, were found in the ethnic minority group. This result could be attributed mainly to the Moroccan-Dutch and Turkish-Dutch subgroups, who also presented with more depression symptoms when the groups were examined separately. The ethnic minority group displayed a lower level of ethnic group identity compared to the immigrants of the International Comparative Study of Ethnocultural Youth (ICSEY). Ethnic identity was inversely related to symptoms in the Moroccan-Dutch patient group. The prevalence of more severe negative symptoms and depression symptoms in ethnic minority groups deserves more attention, as the experience of attenuated positive symptoms when accompanied by negative symptoms or distress has proven to be predictive for transition to a first psychotic episod

Antipsychotic treatment strategies and early course of first episode psychosis

Schizofrenie is een psychische aandoening, die onder meer gepaard gaat met psychoses: periodes waarin de patiënt het normale contact met de werkelijkheid kwijt is. Met behulp van medicijnen kunnen psychoses onderdrukt worden. Patiënten die hersteld zijn van een psychose willen dikwijls stoppen met medicatie. De risico’s, kans van slagen en eventuele voordelen van een poging om te stoppen na herstel van een eerste psychose waren tot nu toe onbekend. Uit promotieonderzoek van psychiater Lex Wunderink blijkt dat het verantwoord is na stabiele vermindering van de ziekteverschijnselen van een zogeheten ‘eerste episode psychose’ te proberen de antipsychotische medicatie te stoppen, mits onder condities van zorgvuldige monitoring en na nadrukkelijke toestemming van de patiënt. Bij een op de vijf patiënten in de onderzochte patiëntengroep lukte het de medicatie zonder problemen gedurende de resterende follow-up te staken. Bij de overige patiënten moest medicatie worden hervat of traden al bij het stoppen van de medicatie problemen op

Changing Vistas of Psychosis and Antipsychotic Drug Dosing Toward Personalized Management of Antipsychotics in Clinical Practice

Objective: To discuss current evidence on tapering antipsychotic drugs in view of changing vistas of psychosis, suggesting a provisional framework for safely tapering antipsychotic drugs to an optimal low dose, in collaboration with patients and their relatives, to promote functional recovery while preventing relapse. Methods: Paradigm shifts during recent years regarding the nature of psychotic disorders and the role of the dopamine system are discussed, including the positive effects of dopamine blockade in acute psychosis and the limitations and drawbacks of dopamine blockade regarding negative and cognitive symptoms after remission of positive symptoms. Recent advances in tapering strategies and upcoming ways to solve the dilemma between the need to prevent relapses with antipsychotics on the one hand and the need to minimize side effects by tapering these drugs on the other are presented. Results: Modern tapering strategies appear to reduce relapse risk to acceptable levels and offer a feasible personalized option to find the least effective dose to treat and prevent positive symptoms without redundant side effects and functional incapacity. These findings need replication, and several trials that might provide more certainty are on their way. Conclusions and Implications for Practice: Preliminary evidence and clinical experience indicate that personalized dose reduction of antipsychotics is feasible and safe if carried out in close collaboration with patients and their relatives, according to a provisionally suggested framework presented here. These preliminary directions still must be confirmed, revised, and adjusted according to upcoming trial results.</p

The Validity of the 16-Item Version of the Prodromal Questionnaire (PQ-16) to Screen for Ultra High Risk of Developing Psychosis in the General Help-Seeking Population

In order to bring about implementation of routine screening for psychosis risk, a brief version of the Prodromal Questionnaire (PQ; Loewy et al., 2005) was developed and tested in a general help-seeking population. We assessed a consecutive patient sample of 3533 young adults who were help-seeking for nonpsychotic disorders at the secondary mental health services in the Hague with the PQ. We performed logistic regression analyses and CHi-squared Automatic Interaction Detector decision tree analysis to shorten the original 92 items. Receiver operating characteristic curves were used to examine the psychometric properties of the PQ-16. In the general help-seeking population, a cutoff score of 6 or more positively answered items on the 16-item version of the PQ produced correct classification of Comprehensive Assessment of At-Risk Mental State (Yung et al., 2005) psychosis risk/clinical psychosis in 44% of the cases, distinguishing Comprehensive Assessment of At-Risk Mental States (CAARMS) diagnosis from no CAARMS diagnosis with high sensitivity (87%) and specificity (87%). These results were comparable to the PQ-92. The PQ-16 is a good self-report screen for use in secondary mental health care services to select subjects for interviewing for psychosis risk. The low number of items makes it quite appropriate for screening large help-seeking populations, thus enhancing the feasibility of detection and treatment of ultra high-risk patients in routine mental health services. © The Author 2012