Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers

Background Colorectal, endometrial and upper urinary tract tumours are characteristic for Lynch syndrome (hereditary non-polyposis colon carcinoma, HNPCC). The aim of the present study was to establish whether carriers of mutations in mismatch repair genes MLH1, MSH2 or MSH6 are at increased risk of urinary bladder cancer. Methods Carriers and first degree relatives of 95 families with a germline mutation in the MLH1 (n=26), MSH2 (n=43), or MSH6 (n=26) gene were systematically questioned about the occurrence of carcinoma. The cumulative risk of cancer occurring before the age of 70 years (CR70) was compared to the CR70 of the general Dutch population. Microsatellite instability (MSI) testing and/or immunohistochemistry (IHC) for mismatch repair proteins was performed on bladder tumour tissue. Results Bladder cancer was diagnosed in 21 patients (90% men) from 19 Lynch syndrome families (2 MLH1, 15 MSH2, and 4 MSH6). CR70 for bladder cancer was 7.5% (95% CI 3.1% to 11.9%) for men and 1.0% (95% CI 0% to 2.4%) for women, resulting in relative risks for mutation carriers and first degree relatives of 4.2 (95% CI 2.2 to 7.2) for men and 2.2 (95% CI 0.3 to 8.0) for women. Men carrying an MSH2 mutation and their first degree relatives were at highest risks: CR70 for bladder and upper urinary tract cancer being 12.3% (95% CI 4.3% to 20.3%) and 5.9% (95% CI 0.7% to 11.1%). Bladder cancer tissue was MSI positive in 6/7 tumours and loss of IHC staining was found in 14/17 tumours, indicating Lynch syndrome aetiology. Conclusion Patients with Lynch syndrome carrying an MSH2 mutation are at increased risk of urinary tract cancer including bladder cancer. In these cases surveillance should be considered.
Equation-free mechanistic ecosystem forecasting using empirical dynamic modeling

Significance The conventional parametric approach to modeling relies on hypothesized equations to approximate mechanistic processes. Although there are known limitations in using an assumed set of equations, parametric models remain widely used to test for interactions, make predictions, and guide management decisions. Here, we show that these objectives are better addressed using an alternative equation-free approach, empirical dynamic modeling (EDM). Applied to Fraser River sockeye salmon, EDM models (i) recover the mechanistic relationship between the environment and population biology that fisheries models dismiss as insignificant, (ii) produce significantly better forecasts compared with contemporary fisheries models, and (iii) explicitly link control parameters (spawning abundance) and ecosystem objectives (future recruitment), producing models that are suitable for current management frameworks. It is well known that current equilibrium-based models fall short as predictive descriptions of natural ecosystems, and particularly of fisheries systems that exhibit nonlinear dynamics. For example, model parameters assumed to be fixed constants may actually vary in time, models may fit well to existing data but lack out-of-sample predictive skill, and key driving variables may be misidentified due to transient (mirage) correlations that are common in nonlinear systems. With these frailties, it is somewhat surprising that static equilibrium models continue to be widely used. Here, we examine empirical dynamic modeling (EDM) as an alternative to imposed model equations and that accommodates both nonequilibrium dynamics and nonlinearity. Using time series from nine stocks of sockeye salmon (Oncorhynchus nerka) from the Fraser River system in British Columbia, Canada, we perform, for the the first time to our knowledge, real-data comparison of contemporary fisheries models with equivalent EDM formulations that explicitly use spawning stock and environmental variables to forecast recruitment. We find that EDM models produce more accurate and precise forecasts, and unlike extensions of the classic Ricker spawner–recruit equation, they show significant improvements when environmental factors are included. Our analysis demonstrates the strategic utility of EDM for incorporating environmental influences into fisheries forecasts and, more generally, for providing insight into how environmental factors can operate in forecast models, thus paving the way for equation-free mechanistic forecasting to be applied in management contexts.
Endoscopic management of a traumatic disruption of the bulbous urethra using a thin trocar puncture

Abstract A case is reported in which complete disruption of the bulbous urethra resulted in a straddled‐type injury, which was managed by endoscopic realignment with a thin trocar needle. The endoscopic urethroplasty consisted of: (i) direct observation of the proximal end of the obliterated urethra by an antegrade flexible cystoscope; (ii) adjustment of the direction of trocar penetration under fluoroscopy and direct vision; (iii) confirmation of the exact trocar position and penetration by antegrade flexible cystoscope; and (iv) placement of the guidewire following the trocar penetration as guidance for urethrotomy. A Foley catheter was left in place for 6 weeks. To date, no further endoscopic revision has been required. Although long‐term follow up and more experience are required, this technique is reported because it appears to be safe, reproducible, simple and minimally invasive.
Ethnographic assessment of an alternative to incarceration for women with minor children.

Allowing criminal justice-involved women to remain with their children in the community may decrease some of the negative intergenerational effects of incarceration. Little is known about potential program models to safely support community coresidence in this population. Ethnographic methods were used to explore the historical development of and life within a supportive housing alternative to incarceration (ATI) program for women with minor children and the health and social needs of resident families. Participants included 8 current and former adult tenants, 12 of their resident children, 3 program staff, the program administrator, and 5 prosecutors who originally conceptualized it. Women also reported information about their 8 nonresident children. Analysis revealed 3 major themes: "The Cycle," "This is My Home," and "This Doesn't Go With That. " While the program built on a core value of family preservation, results illustrate that keeping families together is only the beginning. Clinical and research implications for coresidence ATI programs are discussed in relation to the uniqueness of this context and population.
Accepting or declining the offer of prenatal screening for congenital defects: test uptake and women's reasons

Prenatal screening for Down syndrome has become standard practice in many western countries. In the Netherlands, however, prenatal screening tests for congenital defects are not offered routinely. The present study aims to assess test uptake in a large, unselected population of pregnant women, and to give more insight into the decision for or against prenatal screening through nuchal translucency measurement or maternal serum screening.
Strengthening capacity to apply health research evidence in policy making: experience from four countries

Increasing the use of evidence in policy making means strengthening capacity on both the supply and demand sides of evidence production. However, little experience of strengthening the capacity of policy makers in low- and middle- income countries has been published to date. We describe the experiences of five projects (in Bangladesh, Gambia, India and Nigeria), where collaborative teams of researchers and policy makers/policy influencers worked to strengthen policy maker capacity to increase the use of evidence in policy. Activities were focused on three (interlinked) levels of capacity building: individual, organizational and, occasionally, institutional. Interventions included increasing access to research/data, promoting frequent interactions between researchers and members of the policy communities, and increasing the receptivity towards research/data in policy making or policy-implementing organizations. Teams were successful in building the capacity of individuals to access, understand and use evidence/data. Strengthening organizational capacity generally involved support to infrastructure (e.g. through information technology resources) and was also deemed to be successful. There was less appetite to address the need to strengthen institutional capacity—although this was acknowledged to be fundamental to promoting sustainable use of evidence, it was also recognized as requiring resources, legitimacy and regulatory support from policy makers. Evaluation across the three spheres of capacity building was made more challenging by the lack of agreed upon evaluation frameworks. In this article, we propose a new framework for assessing the impact of capacity strengthening activities to promote the use of evidence/data in policy making. Our evaluation concluded that strengthening the capacity of individuals and organizations is an important but likely insufficient step in ensuring the use of evidence/data in policy-cycles. Sustainability of evidence-informed policy making requires strengthening institutional capacity, as well as understanding and addressing the political environment, and particularly the incentives facing policy makers that supports the use of evidence in policy cycles.
Antiarrhythmic effects of preconditioning in anaesthetised dogs and rats.

OBJECTIVE The aim was to determine the relationship of the duration of short coronary artery occlusions and of the reperfusion period to the extent of the antiarrhythmic effect of preconditioning. METHODS A prolonged occlusion of a coronary artery in 102 anaesthetised rats and 55 anaesthetised dogs was preceded by a variable number of preconditioning coronary artery occlusions, of varying duration and with variable reperfusion periods between them and the prolonged occlusion. RESULTS Preconditioning in both species reduced the severity of ischaemia induced arrhythmias, epicardial ST segment changes, and alterations in the degree of inhomogeneity of conduction during a subsequent prolonged coronary artery occlusion, provided that the reperfusion time was less than 30 min (in rats) and 1 h (in dogs). This antiarrhythmic effect of preconditioning was marked; eg, in dogs following two preconditioning occlusions survival from a combined ischaemia-reperfusion insult was 40% (cf, 0% in the controls). CONCLUSIONS Short preconditioning periods of myocardial ischaemia protect the myocardium against the arrhythmogenic effects of a more prolonged occlusion. The optimum time for this preconditioning occlusion in rats is 3 min and protection is still apparent 30 min later. In dogs, the protective effect is especially clear with two short (5 min) coronary artery occlusions. The protection in this species lasts for less than 1 h.
The Teaming Curve: A Longitudinal Study of the Influence of Surgical Team Familiarity on Operative Time

Objective: To quantify the association between surgical team familiarity and operative time. Background: Team familiarity in the operating room may influence outcomes irrespective of individual surgeons' experience. To date, however, quantifying the impact of teamwork on outcomes has been challenging. Methods: We studied 754 bilateral reduction mammaplasty procedures performed by 223 teams, comprising 8 attending surgeons and 107 assisting surgeons, at a major academic hospital between 1995 and 2007. For each procedure, the operative experience of the attending and assisting surgeons and the number of mammaplasty procedures they had previously performed in collaboration were determined. The influence of these factors on operative time was quantified along with patient age, volume of breast reduction, and comorbidities, using multivariate generalized estimating equations. Results: The mean operative time was 153 (SD = 38) minutes for teams with no prior collaborations, 132 (SD = 33) minutes for teams with 1 to 5 collaborations, 116 (SD = 23) minutes for teams with 6 to 10 collaborations, and 119 (SD = 27) minutes for teams with more than 10 collaborations (P = 0.0001). Operative time was independently associated with the operative experience of the attending (P = 0.02) and assisting surgeons (P = 0.03) and the number of prior collaborations between them (P < 0.001). The expected reductions in operative time over the attending surgeon's career and the assisting surgeon's training period were 59 and 22 minutes, respectively. Surgical team familiarity accounted for an additional reduction of 16 minutes after 10 prior collaborations. Conclusions: In addition to individual surgeon experience, team familiarity contributed to reductions in operative time, suggesting potential benefits to maintaining continuity of team membership over time.
Handling and storage of human body fluids for analysis of extracellular vesicles

Because procedures of handling and storage of body fluids affect numbers and composition of extracellular vesicles (EVs), standardization is important to ensure reliable and comparable measurements of EVs in a clinical environment. We aimed to develop standard protocols for handling and storage of human body fluids for EV analysis. Conditions such as centrifugation, single freeze–thaw cycle, effect of time delay between blood collection and plasma preparation and storage were investigated. Plasma is the most commonly studied body fluid in EV research. We mainly focused on EVs originating from platelets and erythrocytes and investigated the behaviour of these 2 types of EVs independently as well as in plasma samples of healthy subjects. EVs in urine and saliva were also studied for comparison. All samples were analysed simultaneously before and after freeze–thawing by resistive pulse sensing, nanoparticle tracking analysis, conventional flow cytometry (FCM) and transmission (scanning) electron microscopy. Our main finding is that the effect of centrifugation markedly depends on the cellular origin of EVs. Whereas erythrocyte EVs remain present as single EVs after centrifugation, platelet EVs form aggregates, which affect their measured concentration in plasma. Single erythrocyte and platelet EVs are present mainly in the range of 100–200 nm, far below the lower limit of what can be measured by conventional FCM. Furthermore, the effects of single freeze–thaw cycle, time delay between blood collection and plasma preparation up to 1 hour and storage up to 1 year are insignificant (p>0.05) on the measured concentration and diameter of EVs from erythrocyte and platelet concentrates and EVs in plasma, urine and saliva. In conclusion, in standard protocols for EV studies, centrifugation to isolate EVs from collected body fluids should be avoided. Freezing and storage of collected body fluids, albeit their insignificant effects, should be performed identically for comparative EV studies and to create reliable biorepositories.
Auditory Brainstem Response Changes during Exposure to GSM-900 Radiation: An Experimental Study

The objective of the present study was to investigate the possible electrophysiological time-related changes in auditory pathway during mobile phone electromagnetic field exposure. Thirty healthy rabbits were enrolled in an experimental study of exposure to GSM-900 radiation for 60 min and auditory brainstem responses (ABRs) were recorded at regular time-intervals during exposure. The study subjects were radiated via an adjustable power and frequency radio transmitter for GSM-900 mobile phone emission simulation, designed and manufactured according to the needs of the experiment. The mean absolute latency of waves III–V showed a statistically significant delay (p < 0.05) after 60, 45 and 15 min of exposure to electromagnetic radiation of 900 MHz, respectively. Interwave latency I–III was found to be prolonged after 60 min of radiation exposure in correspondence to wave III absolute latency delay. Interwave latencies I–V and III–V were found with a statistically significant delay (p < 0.05) after 30 min of radiation. No statistically significant delay was found for the same ABR parameters in recordings from the ear contralateral to the radiation source at 60 min radiation exposure compared with baseline ABR. The ABR measurements returned to baseline recordings 24 h after the exposure to electromagnetic radiation of 900 MHz. The prolongation of interval latencies I–V and III–V indicates that exposure to electromagnetic fields emitted by mobile phone can affect the normal electrophysiological activity of the auditory system, and these findings fit the pattern of general responses to a stressor.
Prevalence of demarcated hypomineralisation defects in second primary molars in Iraqi children.

BACKGROUND Demarcated hypomineralization lesions are not uncommon in second primary molars. Data on the prevalence of hypomineralized second primary molars (HSPM) are scarce. AIM To investigate the prevalence of HSPM, assess the relationship between HSPM and first permanent molars previously diagnosed with demarcated lesions and to determine the severity of HSPM in relation to dental caries severity. DESIGN A cluster sample of 809, 7- to 9-year-old children was examined. The scoring criteria proposed by the European Academy of Paediatric Dentistry for hypomineralization in permanent dentition were adapted to score HSPMs. The International Caries Detection and Assessment System was used to assess caries status in the second primary molar of the children diagnosed with demarcated defects. The examination was carried out in schools by a calibrated dentist. RESULTS Of the children examined, 53 (6.6%) had hypomineralization defects in at least one second primary molar. Combinations of affected first permanent and second primary molars were reported in 21 (39.6%) of cases. Severe carious lesions were found mostly in teeth with enamel breakdown. CONCLUSIONS The prevalence of HSPM was 6.6%. Over one-third of affected second primary molars were associated with demarcated lesions in the first permanent molars. The chance of severe caries increased with the increase in the demarcated lesion severity.
Why Do Adolescents Drink? Motivational Patterns Related to Alcohol Consumption and Alcohol-Related Problems

The present study was designed to investigate motivational patterns for drinking alcohol and their relation about alcohol consumption and problems related to alcohol consumption. Data were collected by semistructured interviews and questionnaires, containing questions about reasons for drinking, alcohol consumption, and problems related to alcohol consumption during the years 2001, 2004, and 2005. Three independent population samples from two different counties of central Sweden were included. A total of 11,167 adolescents participated. Data on reasons for drinking were analyzed by factor analysis to extract components explaining drinking motives. Relationships between motivational patterns and alcohol use were examined with correlation analysis. Three drinking motives emerged (social-enhancement, coping, and dominance motives) and related to alcohol consumption and problems related to alcohol consumption. Limitations of the study are noted and discussed.
Bilateral quadriceps tendon rupture in a seasoned marathon runner with patellar spurs

We present the case of a healthy seasoned marathon runner who sustained bilateral quadriceps tendon rupture following a low-energy fall. Radiographs demonstrated bilateral patellar spurs. Our case report serves to highlight the importance of maintaining a high index of clinical suspicion in patients of all ages. This is the first report of bilateral quadriceps rupture in the presence of bilateral patellar spurs.
A Polycomb response element in the Ubx gene that determines an epigenetically inherited state of repression.

Segmentation genes provide the signals for the activation and regulation of homeotic genes in Drosophila but cannot maintain the resulting pattern of expression because their activity ceases halfway through embryogenesis. Maintenance of the pattern is due to the Polycomb group of genes (Pc‐G) and the trithorax group of genes (trx‐G), responsible for the persistence of the active or repressed state of homeotic genes. We have identified a regulatory element in the Ubx gene that responds to Pc‐G and trx‐G genes. Transposons carrying this element create new binding sites for Pc‐G products in the polytene chromosomes. This Pc‐G maintenance element (PRE), establishes a repressive complex that keeps enhancers repressed in cells in which they were originally repressed and maintains this state through many cell divisions. The trx‐G products stimulate the expression of enhancers in cells in which they were originally active. This mechanism is responsible for the correct regulation of imaginal disc enhancers, which lack themselves antero‐posterior positional information. The PRE also causes severe variegation of the mini‐white gene present in the transposon, a phenomenon very similar to heterochromatic position‐effect variegation. The significance of this mechanism for homeotic gene regulation is discussed.
Highly-configurable FPGA-based platform for wireless network research

Over the past few years, researchers have developed many cross-layer wireless protocols to improve the performance of wireless networks. Experimental evaluations of these protocols require both high-speed simulations and real-time on-air experimentations. Unfortunately, radios implemented in pure software are usually inadequate for either because they are typically two to three orders of magnitude slower than commodity hardware. FPGA-based platforms provide much better speeds but are quite difficult to modify because of the way high-speed designs are typically implemented by trading modularity for performance. Experimenting with cross-layer protocols requires a flexible way to convey information beyond the data itself from lower to higher layers, and a way for higher layers to configure lower layers dynamically and within some latency bounds. One also needs to be able to modify a layer's processing pipeline without triggering a cascade of changes. In this thesis, we discuss an alternative approach to implement a high-performance yet configurable radio design on an FPGA platform that satisfies these requirements. We propose that all modules in the design must possess two important design properties, namely latency-insensitivity and data-driven control, which facilitate modular refinements. We have developed Airblue, an FPGA-based radio, that has all these properties and runs at speeds comparable to commodity hardware. Our baseline design is 802.11g compliant and is able to achieve reliable communication for bit rates up to 24 Mbps. We show in the thesis that we can implement SoftRate, a cross-layer rate adaptation protocol, by modifying only 5.6% of the source code (967 lines). We also show that our modular design approach allows us to abstract the details of the FPGA platform from the main design, thus making the design portable across multiple FPGA platforms. By taking advantage of this virtualization capability, we were able to turn Airblue into a high-speed hardware software co-simulator with simulation speed beyond 20 Mbps. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)