Team dynamics and clinician's experience influence decision-making during Upper-GI multidisciplinary team meetings: A multiple case study.

Background: The probability of undergoing treatment with curative intent for esophagogastric cancer has been shown to vary considerately between hospitals of diagnosis. Little is known about the factors that attribute to this variation. Since clinical decision making (CDM) partially takes place during an MDTM, the aim of this qualitative study was to assess clinician's perspectives regarding facilitators and barriers associated with CDM during MDTM, and second, to identify factors associated with CDM during an MDTM that may potentially explain differences in hospital practice. Methods: A multiple case study design was conducted. The thematic content analysis of this qualitative study, focused on 16 MDTM observations, 30 semi-structured interviews with clinicians and seven focus groups with clinicians to complement the collected data. Interviews were transcribed ad verbatim and coded. Results: Factors regarding team dynamics that were raised as aspects attributing to CDM were clinician's personal characteristics such as ambition and the intention to be innovative. Clinician's convictions regarding a certain treatment and its outcomes and previous experiences with treatment outcomes, and team dynamics within the MDTM influenced CDM. In addition, a continuum was illustrated. At one end of the continuum, teams tended to be more conservative, following the guidelines more strictly, versus the opposite in which hospitals tended towards a more invasive approach maximizing the probability of curation. Conclusion: This study contributes to the awareness that variation in team dynamics influences CDM during an MDTM.

Cross-calibration of a combined electrostatic and time-of-flight analyzer for energy- and charge-state-resolved spectrometry of tin laser-produced plasma.

We present the results of the calibration of a channeltron-based electrostatic analyzer operating in time-of-flight mode (ESA-ToF) using tin ions resulting from laser-produced plasma, over a wide range of charge states and energies. Specifically, the channeltron electron multiplier detection efficiency and the spectrometer resolution are calibrated, and count rate effects are characterized. With the obtained overall response function, the ESA-ToF is shown to accurately reproduce charge-integrated measurements separately and simultaneously obtained from a Faraday cup (FC), up to a constant factor the finding of which enables absolute cross-calibration of the ESA-ToF using the FC as an absolute benchmark. Absolute charge-state-resolved ion energy distributions are obtained from ns-pulse Nd:YAG-laser-produced microdroplet tin plasmas in a setting relevant for state-of-the-art extreme ultraviolet nanolithography.

The Impact of Tumor Regression on Prognosis After Neoadjuvant Chemoradiotherapy in Surgically Treated Esophageal Adenocarcinoma.

BACKGROUND: The 5-year survival for patients with esophageal carcinoma remains poor despite neoadjuvant therapy and surgery. The eighth American Joint Committee on Cancer (AJCC) staging, based on the neoadjuvant treated TNM (ypTNM) stage of the resection specimen, is used for prognosis. Tumor characteristics such as tumor grade, subtype of adenocarcinoma, and tumor regression scores are not included in this classification. This study aimed to determine the impact of these tumor characteristics on overall survival (OS) and disease-free survival (DFS). METHODS: This retrospective cohort study included 228 patients with esophageal adenocarcinoma. Tumor regression was determined by the Mandard tumor regression (MTR) score. Subtype and grade of adenocarcinoma were confirmed using either the preoperative biopsy or residual tumor tissue after surgery. The MTR was modified to a three-tier classification. The study classified MTR 1 and 2 in one group as a "major response," with MTR 4 and 5 classified in one group as a "minimal response." RESULTS: The median follow-up period was 2.1 years. Combining MTR with AJCC staging did not improve the prognostic value for the prediction of OS. However, the multivariate analysis showed that the prognostic value of AJCC staging for DFS was improved by adding the three-tiered MTR (odds ratio for MTR4+5: 2.46; 95 % confidence interval, 1.07-5.67). Grade or subtype correlated with neither OS nor DFS in the univariate analyses and did not improve the prognostic value of the AJCC staging. CONCLUSION: Neither adenocarcinoma subtype nor grade influenced OS or DFS. However, the eighth AJCC staging combined with a three-tier MTR provided a better prognostic tool for DFS in esophageal adenocarcinoma treated with esophagectomy after neoadjuvant chemoradiotherapy.

Preoperative PSMA-PET/CT as a predictor of biochemical persistence and early recurrence following radical prostatectomy with lymph node dissection.

BACKGROUND: This study aims to evaluate the predictive value of lymph nodes (LN) suspicious for metastases on preoperative prostate-specific membrane antigen (PSMA) PET/CT for biochemical persistence (BCP) and early biochemical recurrence (BCR) following robotic-assisted radical prostatectomy (RARP) with extended pelvic LN dissection (ePLND). METHODS: We evaluated 213 patients with intermediate and high-risk prostate cancer (PCa) who underwent clinical staging with preoperative 68Ga- or 18F-PSMA-PET/CT scan and subsequent RARP with ePLND. Patients were grouped as PSMA- or PSMA+ depending on their LN status on PSMA-PET/CT and subdivided according to histological LN status in pN0 or pN1. Diagnostic accuracy of PSMA-PET/CT for the detection of pN1 was evaluated. BCP was defined as a first postoperative serum PSA level ≥0.1 ng/mL 6-12 weeks following RP. Early BCR was defined as detectable PSA > 0.2 ng/mL within 12 months of follow-up. Univariable logistic regression analyses were used to evaluate the effect of PSMA+ on BCP and BCR. RESULTS: Forty patients (19%) were PSMA+. The overall incidence of pN1 was 23%. Sensitivity, specificity, PPV and NPV on a per patient level for the detection of pN1 was 29%, 84%, 35%, and 80% respectively. BCP was observed in 26 of 211 patients (12%) and early BCR in 23 of 110 patients (21%). The presence of PSMA+ was a significant predictor for BCP (OR 7.1, 2.9-17.1 95% CI) and BCR (OR 8.1, 2.9-22.6 95% CI). CONCLUSION: Preoperative PSMA-PET/CT may be a valuable tool for patient counseling for RARP and ePLND as it is a significant predictor for the risk of postoperative BCP and early BCR. We conclude that an ePLND should not be avoided in men with intermediate or high-risk PCa and preoperative negative PSMA-PET/CT, as 20% have microscopic LN metastasis.

Extreme ultraviolet light from a tin plasma driven by a 2-µm-wavelength laser.

An experimental study of laser-produced plasmas is performed by irradiating a planar tin target by laser pulses, of 4.8 ns duration, produced from a KTP-based 2-µm-wavelength master oscillator power amplifier. Comparative spectroscopic investigations are performed for plasmas driven by 1-µm- and 2-µm-wavelength pulsed lasers, over a wide range of laser intensities spanning 0.5 - 5 × 1011 W/cm 2. Similar extreme ultraviolet (EUV) spectra in the 5.5-25.5 nm wavelength range and underlying plasma ionicities are obtained when the intensity ratio is kept fixed at I1µm/I2µm = 2.4(7). Crucially, the conversion efficiency (CE) of 2-µm-laser energy into radiation within a 2% bandwidth centered at 13.5 nm relevant for industrial applications is found to be a factor of two larger, at a 60 degree observation angle, than in the case of the denser 1-µm-laser-driven plasma. Our findings regarding the scaling of the optimum laser intensity for efficient EUV generation and CE with drive laser wavelength are extended to other laser wavelengths using available literature data.

Foods Implicated in U.S. Outbreaks Differ from the Types Most Commonly Consumed.

ABSTRACT: Foodborne disease outbreak investigations identify foods responsible for illnesses. However, it is not known the degree to which foods implicated in outbreaks reflect the distribution of food consumption in the U.S. population or the risk associated with their consumption. We compared the distribution of 24 categories of foods implicated in outbreaks with the distribution of foods consumed by the U.S. population. Beef, chicken, eggs, fish, herbs, mollusks, pork, sprouts, seeded vegetables, and turkey were implicated in outbreaks significantly more often than expected based on the frequency of their consumption by the general population, suggesting a higher risk of contamination or mishandling from foods in these categories than from foods in other categories. In contrast, pasteurized dairy, fruits, grains and beans, oils and sugars, and root and underground vegetables were less frequently implicated in outbreaks than their frequency of consumption by the general population, suggesting a lower health risk associated with these food categories.

Recency-Weighted Statistical Modeling Approach to Attribute Illnesses Caused by 4 Pathogens to Food Sources Using Outbreak Data, United States.

Foodborne illness source attribution is foundational to a risk-based food safety system. We describe a method for attributing US foodborne illnesses caused by nontyphoidal Salmonella enterica, Escherichia coli O157, Listeria monocytogenes, and Campylobacter to 17 food categories using statistical modeling of outbreak data. This method adjusts for epidemiologic factors associated with outbreak size, down-weights older outbreaks, and estimates credibility intervals. On the basis of 952 reported outbreaks and 32,802 illnesses during 1998-2012, we attribute 77% of foodborne Salmonella illnesses to 7 food categories (seeded vegetables, eggs, chicken, other produce, pork, beef, and fruits), 82% of E. coli O157 illnesses to beef and vegetable row crops, 81% of L. monocytogenes illnesses to fruits and dairy, and 74% of Campylobacter illnesses to dairy and chicken. However, because Campylobacter outbreaks probably overrepresent dairy as a source of nonoutbreak campylobacteriosis, we caution against using these Campylobacter attribution estimates without further adjustment.

Time- and space-resolved optical Stark spectroscopy in the afterglow of laser-produced tin-droplet plasma.

The afterglow emission from Nd:YAG-laser-produced microdroplet-tin plasma is investigated, with a focus on analyzing Stark effect phenomena and the dynamical evolution of the plasma. Time- and space-resolved optical imaging spectroscopy is performed on 11 lines from Sn i-iv ions, in the 315-425-nm wavelength range. Stark shift-to-width ratios serve as the basis for unambiguous experimental tests of atomic physics theory predictions. Experiment and theory, where available, are found to be in poor agreement, and are in disagreement regarding the sign of the ratio in several cases. Spectroscopic measurements of the Stark widths in tandem with Saha-Boltzmann fits to Sn i and Sn ii lines, establish the evolution of the local temperature and density of the plasma afterglow, 20-40 ns after the end of the 15-ns-long temporally box-shaped laser pulse. A clear cool-down from ∼2 to 1 eV is observed of the plasma in this time window, having started at ∼30 eV when emitting extreme-ultraviolet (EUV) light. An exponential reduction of the density of the plasma from ∼10^{18}-10^{17}e^{-} cm^{-3} is observed in this same time window. Our work is relevant for understanding the dynamics of the decaying, expanding plasma in state-of-the-art EUV nanolithography machines.

Prominent radiative contributions from multiply-excited states in laser-produced tin plasma for nanolithography.

Extreme ultraviolet (EUV) lithography is currently entering high-volume manufacturing to enable the continued miniaturization of semiconductor devices. The required EUV light, at 13.5 nm wavelength, is produced in a hot and dense laser-driven tin plasma. The atomic origins of this light are demonstrably poorly understood. Here we calculate detailed tin opacity spectra using the Los Alamos atomic physics suite ATOMIC and validate these calculations with experimental comparisons. Our key finding is that EUV light largely originates from transitions between multiply-excited states, and not from the singly-excited states decaying to the ground state as is the current paradigm. Moreover, we find that transitions between these multiply-excited states also contribute in the same narrow window around 13.5 nm as those originating from singly-excited states, and this striking property holds over a wide range of charge states. We thus reveal the doubly magic behavior of tin and the origins of the EUV light.

Epidemiologic patterns of human Salmonella serotype diversity in the USA, 1996-2016.

Although researchers have described numerous risk factors for salmonellosis and for infection with specific common serotypes, the drivers of Salmonella serotype diversity among human populations remain poorly understood. In this retrospective observational study, we partition records of serotyped non-typhoidal Salmonella isolates from human clinical specimens reported to CDC national surveillance by demographic, geographic and seasonal characteristics and adapt sample-based rarefaction methods from the field of community ecology to study how Salmonella serotype diversity varied within and among these populations in the USA during 1996-2016. We observed substantially higher serotype richness in children <2 years old than in older children and adults and steadily increasing richness with age among older adults. Whereas seasonal and regional variation in serotype diversity was highest among infants and young children, variation by specimen source was highest in adults. Our findings suggest that the risk for infection from uncommon serotypes is associated with host and environmental factors, particularly among infants, young children and older adults. These populations may have a higher proportion of illness acquired through environmental transmission pathways than published source attribution models estimate.

Post-Campylobacter Guillain Barré Syndrome in the USA: secondary analysis of surveillance data collected during the 2009-2010 novel Influenza A (H1N1) vaccination campaign.

Guillain Barré syndrome (GBS), which is triggered by autoantibodies produced in response to antigenic stimuli such as certain infections and vaccinations, is the most common cause of acute flaccid paralysis worldwide. Campylobacter, the most common bacterial enteric infection in the USA, is reported to be the most commonly diagnosed antecedent of GBS, yet little information is available about the risk of post-Campylobacter GBS. Data collected through active, population-based surveillance in the Emerging Infections Program during the 2009-2010 novel Influenza A (H1N1) vaccination campaign allowed us to compare confirmed and probable GBS cases to non-cases to determine whether antecedent Campylobacter infection (or a diarrhoeal illness consistent with campylobacteriosis) was more common among cases and to assess the risk of GBS following Campylobacter infection. We estimate that 8-12% of GBS cases in the USA are attributable to Campylobacter infection (or a diarrhoeal illness consistent with campylobacteriosis), with 434-650 cases of post-diarrhoeal GBS annually and about 49 cases of GBS per 100 000 Campylobacter infections. These results provide updated estimates for post-Campylobacter GBS incidence in the USA and highlight an important benefit of effective measures to prevent Campylobacter infections.

Monitoring of patients treated with lithium for bipolar disorder: an international survey.

BACKGROUND: Adequate monitoring of patients using lithium is needed for optimal dosing and for early identification of patients with (potential) ADEs. The objective was to internationally assess how health care professionals monitor patients treated with lithium for bipolar disorder. METHODS: Using networks of various professional organizations, an anonymous online survey was conducted among health care professionals prescribing lithium. Target lithium serum levels and frequency of monitoring was assessed together with monitoring of physical and laboratory parameters. Reasons to and not to monitor and use of guidelines and institutional protocols, and local monitoring systems were investigated. RESULTS: The survey was completed by 117 health care professionals incorporating responses from twenty-four countries. All prescribers reported to monitor lithium serum levels on a regular basis, with varying target ranges. Almost all (> 97%) monitored thyroid and renal function before start and during maintenance treatment. Reported monitoring of other laboratory and physical parameters was variable. The majority of respondents (74%) used guidelines or institutional protocols for monitoring. In general, the prescriber was responsible for monitoring, had to request every monitoring parameter separately and only a minority of patients was automatically invited. CONCLUSIONS: Lithium serum levels, renal and thyroid function were monitored by (almost) all physicians. However, there was considerable variation in other monitoring parameters. Our results help to understand why prescribers of lithium monitor patients and what their main reasons are not to monitor patients using lithium.

[Incidence of incontinence after radical prostatectomy using claims-based data]. / Hoe vaak incontinentie na radicale prostatectomie?

OBJECTIVE: To determine the effect of radical prostatectomy (RP) hospital volume on the probability of post-RP incontinence. DESIGN: Retrospective research based on claims-based data of health insurers. METHOD: For every patient with RP the probability of incontinence was determined, based on the definition of claims of one or more incontinence pads per day. Casemix corrections were made based on indicators available in claims-data: age, lymph node dissection, and radiotherapy. No casemix corrections could be made for tumour stage and surgical technique. RESULTS: A total of 1590 patients were included in this study; for 26.0% of these patients, an average of one or more incontinence pads per day were claimed for. A significant relation between the volume of RP per hospital and the claims of incontinence material was observed. The probability of incontinence was significantly lower in hospitals with a volume of more than 100 RP patients per year when compared to hospitals with less than 100 RP patients per year. CONCLUSION: The probability of post-RP incontinence decreases as hospitals conduct more RP procedures. The casemix factors included in the analysis only had a limited impact on this observation.

Temporal patterns in principal Salmonella serotypes in the USA; 1996-2014.

Analysing temporal patterns in foodborne illness is important to designing and implementing effective food safety measures. The reported incidence of illness due to Salmonella in the USA. Foodborne Diseases Active Surveillance Network (FoodNet) sites has exhibited no declining trend since 1996; however, there have been significant annual trends among principal Salmonella serotypes, which may exhibit complex seasonal patterns. Data from the original FoodNet sites and penalised cubic B-spline regression are used to estimate temporal patterns in the reported incidence of illness for the top three Salmonella serotypes during 1996-2014. Our results include 95% confidence bands around the estimated annual and monthly curves for each serotype. The results show that Salmonella serotype Typhimurium exhibits a statistically significant declining annual trend and seasonality (P < 0.001) marked by peaks in late summer and early winter. Serotype Enteritidis exhibits a significant annual trend with a higher incidence in later years and seasonality (P < 0.001) marked by a peak in late summer. Serotype Newport exhibits no significant annual trend with significant seasonality (P < 0.001) marked by a peak in late summer.

[Bipolar disorder and alcohol use disorder: practical recommendations for treatment, based on a literature review]. / Bipolaire stoornissen en alcoholafhankelijkheid; praktische aanbevelingen voor behandeling op basis van een systematische literatuurstudie.

BACKGROUND: A fairly large proportion (25-50%) of patients with bipolar disorder (bd) also suffer from comorbid alcohol use disorder (aud). However, little is known how this type of morbidity should be treated. It is also unclear whether the current guidelines on bd have been influenced by aud.
AIM: To provide an overview of recent literature concerning the diagnosis and treatment of comorbid bd and aud.
METHOD: We systematically reviewed studies that have addressed three treatment options for this group of patients: pharmaco-therapy, psychological interventions and self-management techniques.
RESULTS: If health professionals decide to treat bd using a pharmaco-therapeutic intervention, they must proceed with caution because the patient may also be suffering from aud. From the very limited number of published articles on this subject, we conclude that the best solution to the problem is to add valproate to the lithium-based treatment. There is also limited evidence that other effective treatments may include the use of integrated psychological interventions, cognitive behavioural therapy and self-management techniques, but these possibilities need further investigation.
CONCLUSION: Treatment of patients suffering from both bd and aud should always focus on both disorders, either simultaneously or separately. If this approach is successful it is vitally important that care is better organised and that there is cooperation between institutions involved in treating addiction disorders and departments that specialise in the care of bd. These improvements are likely to lead to further developments and to more research into new forms of integrated treatment.

Advances in methods for characterization of hepatic urea cycle enzymatic activity in HepaRG cells using UPLC-MS/MS.

Current methodologies for the assessment of urea cycle (UC) enzymatic activity are insufficient to accurately evaluate this pathway in biological specimens where lower UC is expected. Liver cell lines, including HepaRG, have been described to have limited nitrogen fixation through the UC, limiting their applicability as biocomponents for Bioartificial Livers (BAL). This work aims to develop novel and sensitive analytical solutions using Mass Spectrometry-based methodology to measure the activity of four UC enzymes in human liver and HepaRG cells. Activity of carbamoyl-phosphate synthetase I (CPS I), ornithine transcarbamylase (OTC), argininosuccinate lyase (ASL) and arginase (ARG I and II) was determined on homogenates from normal human liver and HepaRG cells cultured in monolayer or in the AMC-BAL. Enzyme products were determined by stable-isotope dilution UPLC-MS/MS. Activity of CPS I, OTC and ARG I/II enzymes in HepaRG monolayer cultures was considerably lower than in human control livers albeit an increase was achieved in HepaRG-BAL cultures. Improved analytical assays developed for the study of UC enzyme activity, contributed to gain understanding of UC function in the HepaRG cell line. The decreased activity of CPS I suggests that it may be a potential rate-limiting factor underlying the low UC activity in this cell line.

A comparative VUV absorption mass-spectroscopy study on protonated peptides of different size.

The ionization of gas-phase protonated peptides and proteins can induce molecular responses ranging from purely non-dissociative ionization to extensive multifragmentation of the system. In the case of soft X-ray photoionization, a monotonic transition between both regimes occurs in the mass range between 0.5 and 10 kDa. Despite the localized nature of the photoabsorption, excitation energy equilibrates before fragmentation sets in and the transition reflects the increase of the heat capacity with protein size. Here, we have investigated the influence of peptide size on vacuum ultraviolet (VUV) photoionization of protonated proteins, where photoexcitation and ionization are limited to valence electrons rather than inner shell electrons and the photoexcitation contribution is markedly lower. Gas phase protonated peptides with masses ranging from 0.6-2.8 kDa were trapped in a radiofrequency ion trap and exposed to synchrotron radiation. Time of flight mass spectrometry was employed for the investigation of the photoionization and photofragmentation processes. The relationship between peptide fragmentation and peptide size exhibits a similar trend as observed for soft X-ray absorption. Due to the lower excitation energies involved, however, dissociation is already quenched at smaller masses and peptide amino acid compositions, protonation states and ionization potentials lead to deviations from the general trend.

Near edge X-ray absorption mass spectrometry of gas phase proteins: the influence of protein size.

Multiply protonated peptides and proteins in the gas phase can respond to near edge X-ray absorption in three different ways: (i) non dissociative ionization and ionization accompanied by loss of small neutrals, both known to dominate for proteins with masses in the 10 kDa range. (ii) Formation of immonium ions, dominating for peptides in the 1 kDa range. (iii) Backbone scission leading to sequence ions which is typically weaker and has mainly been observed for peptides in the 1 kDa range. We have studied carbon 1s photoexcitation and photoionization for a series of peptides and proteins with masses covering the range from 0.5 kDa to more than 10 kDa. The gas phase protonated molecules were trapped in a radiofrequency ion trap and exposed to synchrotron radiation. Time of flight mass spectrometry was employed for investigation of the photoionization and photofragmentation processes. A smooth transition from the photofragmentation regime to the non-dissociative photoionization regime is observed. Mass spectra are most complex in the few kDa regime, where non-dissociative ionization, backbone scission and immonium ion formation coexist. The observed correlation between protein size and fragmentation, i.e. radiation damage, is of relevance for soft X-ray microscopy.

High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls.

BACKGROUND: Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their relatives have similar lower intellectual and educational performance as that observed in schizophrenia. METHOD: This cross-sectional study investigated intelligence and educational performance in two outpatient samples [494 BD-I patients, 952 schizophrenia spectrum (SCZ) patients], 2231 relatives of BD-I and SCZ patients, 1104 healthy controls and 100 control siblings. Mixed-effects and regression models were used to compare groups on intelligence and educational performance. RESULTS: BD-I patients were more likely to have completed the highest level of education (odds ratio 1.88, 95% confidence interval 1.66-2.70) despite having a lower IQ compared to controls (ß = -9.09, S.E. = 1.27, p < 0.001). In contrast, SCZ patients showed both a lower IQ (ß = -15.31, S.E. = 0.86, p < 0.001) and lower educational levels compared to controls. Siblings of both patient groups had significantly lower IQ than control siblings, but did not differ on educational performance. IQ scores did not differ between BD-I parents and SCZ parents, but BD-I parents had completed higher educational levels. CONCLUSIONS: Although BD-I patients had a lower IQ than controls, they were more likely to have completed the highest level of education. This contrasts with SCZ patients, who showed both intellectual and educational deficits compared to healthy controls. Since relatives of BD-I patients did not demonstrate superior educational performance, our data suggest that high educational performance may be a distinctive feature of bipolar disorder patients.