Development and validation of colorectal cancer risk prediction tools:A comparison of models

Background: Identification of individuals at elevated risk can improve cancer screening programmes by permitting risk-adjusted screening intensities. Previous work introduced a prognostic model using sex, age and two preceding faecal haemoglobin concentrations to predict the risk of colorectal cancer (CRC) in the next screening round. Using data of 3 screening rounds, this model attained an area under the receiver-operating-characteristic curve (AUC) of 0.78 for predicting advanced neoplasia (AN). We validated this existing logistic regression (LR) model and attempted to improve it by applying a more flexible machine-learning approach. Methods: We trained an existing LR and a newly developed random forest (RF) model using updated data from 219,257 third-round participants of the Dutch CRC screening programme until 2018. For both models, we performed two separate out-of-sample validations using 1,137,599 third-round participants after 2018 and 192,793 fourth-round participants from 2020 onwards. We evaluated the AUC and relative risks of the predicted high-risk groups for the outcomes AN and CRC. Results: For third-round participants after 2018, the AUC for predicting AN was 0.77 (95% CI: 0.76–0.77) using LR and 0.77 (95% CI: 0.77–0.77) using RF. For fourth-round participants, the AUCs were 0.73 (95% CI: 0.72–0.74) and 0.73 (95% CI: 0.72–0.74) for the LR and RF models, respectively. For both models, the 5% with the highest predicted risk had a 7-fold risk of AN compared to average, whereas the lowest 80% had a risk below the population average for third-round participants. Conclusion: The LR is a valid risk prediction method in stool-based screening programmes. Although predictive performance declined marginally, the LR model still effectively predicted risk in subsequent screening rounds. An RF did not improve CRC risk prediction compared to an LR, probably due to the limited number of available explanatory variables. The LR remains the preferred prediction tool because of its interpretability.</p

SIMULASI PENDISTRIBUSIAN AIR MINUM PADA SUMBER AIR GUA SEROPAN KABUPATEN GUNUNG KIDUL

Kabupaten Gunung Kidul adalah salah satu wilayah yang mempunyai potensi air berlimpah tapi penduduk kekurangan air. Karena sebagian besar kondisi alamnya merupakan pegunungan kapur, maka digunakan teknologi untuk memperoleh air. Tujuan dari penulisan ini adalah adalah membuat simulasi jam pendistribusian air yang efektif khusus untuk kecamatan Ngawen dengan bantuan program Epanet 2.0, sehingga diperoleh waktu pendistribusian sesuai dengan kebutuhan pelanggan dengan waktu distribusi dilihat dari kebiasaan masyarakat mengkonsumsi atau menggunakan air dalam aktifitas sehari-harinya. Metode yang digunakan pada penulisan ini yaitu deskripsi komperatif yaitu mejelaskan pengaturan pendistribusian air yang terdapat di Kecamatan Ngawen dibandingkan dengan pengaturan simulasi dengan bantuan program Epanet 2.0, sehingga diperoleh simulasi pendistribusian yang efektif. Berdasarkan hasil analisa jaringan air minum kecamatan Ngawen untuk waktu pelayanan kondisi eksisting 12 jam selalu terjadi kekurangan. Sedangkan hasil simulasi jam pendistribusian kecamatan Ngawen untuk waktu distribusi 24 jam masih terjadik kekurangan. Dari hal tersebut diatas perlu adanya penelitian lebih lanjut tentang masalah yang menyebabkan jaringan air minum di kecamatan Ngawen sering terjadi kekurangan

A simulation of skin mitochondrial PO2 in circulatory shock

Circulatory shock is the inadequacy to supply mitochondria with enough oxygen to sustain aerobic energy metabolism. A novel non-invasive bedside measurement was recently introduced to monitor the mitochondrial oxygen tension in the skin (mitoPO2). As the most downstream marker of oxygen balance in the skin, mitoPO2 may provide additional information to improve shock management. However, a physiological basis for the interpretation of mitoPO2 values has not been established yet. In this paper we developed a mathematical model of skin mitoPO2 using a network of parallel microvessels, based on Krogh's cylinder model. The model contains skin blood flow velocity, heterogeneity of blood flow, hematocrit, arteriolar oxygen saturation and mitochondrial oxygen consumption as major variables. The major results of the model show that normal physiological mitoPO2 is in the range of 40-60mmHg. The relationship of mitoPO2 with skin blood flow velocity follows a hyperbolic curve, reaching a plateau at high skin blood flow velocity, suggesting that oxygen balance remains stable whilst peripheral perfusion declines. The model shows that a critical range exists where mitoPO2 rapidly deteriorates if skin perfusion further decreases. The model intuitively shows how tissue hypoxia could occur in the setting of septic shock, due to the profound impact of microcirculatory disturbance on mitoPO2, even at sustained cardiac output. MitoPO2 is the result of a complex interaction between all factors of oxygen delivery and the microcirculation. This mathematical framework can be used to interpret mitoPO2 values in shock, with the potential to enhance personalized clinical trial design.</p

Epidemiology of combined clavicle and rib fractures:a systematic review

Purpose The aim of this systematic review was to provide an overview of the incidence of combined clavicle and rib fractures and the association between these two injuries. Methods A systematic literature search was performed in the MEDLINE, EMBASE, and CENTRAL databases on the 14(th) of August 2020. Outcome measures were incidence, hospital length of stay (HLOS), intensive care unit admission and length of stay (ILOS), duration of mechanical ventilation (DMV), mortality, chest tube duration, Constant-Murley score, union and complications. Results Seven studies with a total of 71,572 patients were included, comprising five studies on epidemiology and two studies on treatment. Among blunt chest trauma patients, 18.6% had concomitant clavicle and rib fractures. The incidence of rib fractures in polytrauma patients with clavicle fractures was 56-60.6% versus 29% in patients without clavicle fractures. Vice versa, 14-18.8% of patients with multiple rib fractures had concomitant clavicle fractures compared to 7.1% in patients without multiple rib fractures. One study reported no complications after fixation of both injuries. Another study on treatment, reported shorter ILOS and less complications among operatively versus conservatively treated patients (5.4 +/- 1.5 versus 21 +/- 13.6 days). Conclusion Clavicle fractures and rib fractures are closely related in polytrauma patients and almost a fifth of all blunt chest trauma patients sustain both injuries. Definitive conclusions could not be drawn on treatment of the combined injury. Future research should further investigate indications and benefits of operative treatment of this injury

Epidemiology and outcome of rib fractures:a nationwide study in the Netherlands

Purpose Rib fractures following thoracic trauma are frequently encountered injuries and associated with a significant morbidity and mortality. The aim of this study was to provide current data on the epidemiology, in-hospital outcomes and 30-day mortality of rib fractures, and to evaluate these results for different subgroups. Methods A nationwide retrospective cohort study was performed with the use of the Dutch Trauma Registry which covers 99% of the acutely admitted Dutch trauma population. All patients aged 18 years and older admitted to the hospital between January 2015 and December 2017 with one or more rib fractures were included. Incidence rates were calculated using demographic data from the Dutch Population Register. Subgroup analyses were performed for flail chest, polytrauma, primary thoracic trauma, and elderly patients. Results A total of 14,850 patients were admitted between 2015 and 2017 with one or more rib fractures, which was 6.0% of all trauma patients. Of these, 573 (3.9%) patients had a flail chest, 4438 (29.9%) were polytrauma patients, 9273 (63.4%) were patients with primary thoracic trauma, and 6663 (44.9%) were elderly patients. The incidence rate of patients with rib fractures for the entire cohort was 29 per 100.000 person-years. The overall 30-day mortality was 6.9% (n = 1208) with higher rates observed in flail chest (11.9%), polytrauma (14.8%), and elderly patients (11.7%). The median hospital length of stay was 6 days (IQR, 3-11) and 37.3% were admitted to the intensive care unit (ICU). Conclusions Rib fractures are a relevant and frequently occurring problem among the trauma population. Subgroup analyses showed that there is a substantial heterogeneity among patients with rib fractures with considerable differences regarding the epidemiology, in-hospital outcomes, and 30-day mortality

The Interplay Between GUT and Flavour Symmetries in a Pati-Salam x S4 Model

Both Grand Unified symmetries and discrete flavour symmetries are appealing ways to describe apparent structures in the gauge and flavour sectors of the Standard Model. Both symmetries put constraints on the high energy behaviour of the theory. This can give rise to unexpected interplay when building models that possess both symmetries. We investigate on the possibility to combine a Pati-Salam model with the discrete flavour symmetry $S_4$ that gives rise to quark-lepton complementarity. Under appropriate assumptions at the GUT scale, the model reproduces fermion masses and mixings both in the quark and in the lepton sectors. We show that in particular the Higgs sector and the running Yukawa couplings are strongly affected by the combined constraints of the Grand Unified and family symmetries. This in turn reduces the phenomenologically viable parameter space, with high energy mass scales confined to a small region and some parameters in the neutrino sector slightly unnatural. In the allowed regions, we can reproduce the quark masses and the CKM matrix. In the lepton sector, we reproduce the charged lepton masses, including bottom-tau unification and the Georgi-Jarlskog relation as well as the two known angles of the PMNS matrix. The neutrino mass spectrum can present a normal or an inverse hierarchy, and only allowing the neutrino parameters to spread into a range of values between $\lambda^{-2}$ and $\lambda^2$, with $\lambda\simeq0.2$. Finally, our model suggests that the reactor mixing angle is close to its current experimental bound.Comment: 62 pages, 4 figures; references added, version accepted for publication in JHE

Validity of the self-administered comorbidity questionnaire in patients with inflammatory bowel disease

Background: The International Consortium for Health Outcomes Measurement has selected the self-administered comorbidity questionnaire (SCQ) to adjust case-mix when comparing outcomes of inflammatory bowel disease (IBD) treatment between healthcare providers. However, the SCQ has not been validated for use in IBD patients. Objectives: We assessed the validity of the SCQ for measuring comorbidities in IBD patients. Design: Cohort study. Methods: We assessed the criterion validity of the SCQ for IBD patients by comparing patient-reported and clinician-reported comorbidities (as noted in the electronic health record) of the 13 diseases of the SCQ using Cohen’s kappa. Construct validity was assessed using the Spearman correlation coefficient between the SCQ and the Charlson Comorbidity Index (CCI), clinician-reported SCQ, quality of life, IBD-related healthcare and productivity costs, prevalence of disability, and IBD disease activity. We assessed responsiveness by correlating changes in the SCQ with changes in healthcare costs, productivity costs, quality of life, and disease activity after 15 months. Results: We included 613 patients. At least fair agreement (κ &gt; 0.20) was found for most comorbidities, but the agreement was slight (κ &lt; 0.20) for stomach disease [κ = 0.19, 95% CI (−0.03; 0.41)], blood disease [κ = 0.02, 95% CI (−0.06; 0.11)], and back pain [κ = 0.18, 95% CI (0.11; 0.25)]. Correlations were found between the SCQ and the clinician-reported SCQ [ρ = 0.60, 95% CI (0.55; 0.66)], CCI [ρ = 0.39, 95% CI (0.31; 0.45)], the prevalence of disability [ρ = 0.23, 95% CI (0.15; 0.32)], and quality of life [ρ = −0.30, 95% CI (−0.37; −0.22)], but not between the SCQ and healthcare or productivity costs or disease activity (|ρ| ⩽ 0.2). A change in the SCQ after 15 months was not correlated with a change in any of the outcomes.Conclusion: The SCQ is a valid tool for measuring comorbidity in IBD patients, but face and content validity should be improved before being used to correct case-mix differences.</p

Quantum photo-thermodynamics on a programmable photonic quantum processor

One of the core questions of quantum physics is how to reconcile the unitary evolution of quantum states, which is information-preserving and time-reversible, with the second law of thermodynamics, which is neither. The resolution to this paradox is to recognize that global unitary evolution of a multi-partite quantum state causes the state of local subsystems to evolve towards maximum-entropy states. In this work, we experimentally demonstrate this effect in linear quantum optics by simultaneously showing the convergence of local quantum states to a generalized Gibbs ensemble constituting a maximum-entropy state under precisely controlled conditions, while using a new, efficient certification method to demonstrate that the state retains global purity. Our quantum states are manipulated by a programmable integrated photonic quantum processor, which simulates arbitrary non-interacting Hamiltonians, demonstrating the universality of this phenomenon. Our results show the potential of photonic devices for quantum simulations involving non-Gaussian states

Genome-Wide Association Study Identifies GPC5 as a Novel Genetic Locus Protective against Sudden Cardiac Arrest

BACKGROUND:Existing studies indicate a significant genetic component for sudden cardiac arrest (SCA) and genome-wide association studies (GWAS) provide an unbiased approach for identification of novel genes. We performed a GWAS to identify genetic determinants of SCA. METHODOLOGY/PRINCIPAL FINDINGS:We used a case-control design within the ongoing Oregon Sudden Unexpected Death Study (Oregon-SUDS). Cases (n = 424) were SCAs with coronary artery disease (CAD) among residents of Portland, OR (2002-07, population approximately 1,000,000) and controls (n = 226) were residents with CAD, but no history of SCA. All subjects were of White-European ancestry and GWAS was performed using Affymetrix 500K/5.0 and 6.0 arrays. High signal markers were genotyped in SCA cases (n = 521) identified from the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) (combined n = 19,611). No SNPs reached genome-wide significance (p<5x10(-8)). SNPs at 6 loci were prioritized for follow-up primarily based on significance of p<10(-4) and proximity to a known gene (CSMD2, GPR37L1, LIN9, B4GALNT3, GPC5, and ZNF592). The minor allele of GPC5 (GLYPICAN 5, rs3864180) was associated with a lower risk of SCA in Oregon-SUDS, an effect that was also observed in ARIC/CHS whites (p<0.05) and blacks (p<0.04). In a combined Cox proportional hazards model analysis that adjusted for race, the minor allele exhibited a hazard ratio of 0.85 (95% CI 0.74 to 0.98; p<0.01). CONCLUSIONS/SIGNIFICANCE:A novel genetic locus for SCA, GPC5, was identified from Oregon-SUDS and successfully validated in the ARIC and CHS cohorts. Three other members of the Glypican family have been previously implicated in human disease, including cardiac conditions. The mechanism of this specific association requires further study