Using Bayes' rule to define the value of evidence from syndromic surveillance

In this work we propose the adoption of a statistical framework used in the evaluation of forensic evidence as a tool for evaluating and presenting circumstantial "evidence" of a disease outbreak from syndromic surveillance. The basic idea is to exploit the predicted distributions of reported cases to calculate the ratio of the likelihood of observing n cases given an ongoing outbreak over the likelihood of observing n cases given no outbreak. The likelihood ratio defines the Value of Evidence (V). Using Bayes' rule, the prior odds for an ongoing outbreak are multiplied by V to obtain the posterior odds. This approach was applied to time series on the number of horses showing clinical respiratory symptoms or neurological symptoms. The separation between prior beliefs about the probability of an outbreak and the strength of evidence from syndromic surveillance offers a transparent reasoning process suitable for supporting decision makers. The value of evidence can be translated into a verbal statement, as often done in forensics or used for the production of risk maps. Furthermore, a Bayesian approach offers seamless integration of data from syndromic surveillance with results from predictive modeling and with information from other sources such as disease introduction risk assessments.

Ancient History as a Means of Transforming Colonial India in the Late-Eighteenth and Early-Nineteenth Centuries

This article focuses on the studies and discourses of mostly British scholars of the early colonial period belonging to two schools of thought. It shows how the studies of both schools – European orientalism and utilitarianism – were intricately connected to the political development of the emerging British paramountcy over the South Asian sub-continent, as both were looking for means of establishing and/or strengthening colonial rule. Nevertheless, the debate was not just a continuation of discussions in Europe. Whereas the ideas of the European Enlightenment had some influence, the transformation of the Mughal Empire and especially the idea of a decline of Muslim rule offered ample opportunities for understanding the early history of India either as some sort of “Golden Age,” as the orientalists and their indigenous supporters did, or as something static and degenerate, as the utilitarians did, and from which the population of sub-continent had to be saved by colonial rule and colonial values. Fearing the spread of the ideas of the French Revolution, the first group of British scholars sought to persuade the native elites of South Asia to take the lessons of their past for the future development of their homeland. Just as the classicists back in Europe, these scholars were convinced that large-scale explanations of the past could also teach political and moral lessons for the present although it was important to deal with the distant past in an empirical manner. The utilitarians on the other hand believed that India had to be saved from its own depravity through the English language and Western values, which amounted to nothing less than the modern transformation of the true Classical Age.

Δ I = 1 / 2 rule for kaon decays derived from QCD infrared fixed point

This article gives details of our proposal to replace ordinary chiral SU(3)L×SU(3)R perturbation theory χPT3 by three-flavor chiral-scale perturbation theory χPTσ. In χPTσ, amplitudes are expanded at low energies and small u,d,s quark masses about an infrared fixed point αIR of three-flavor QCD. At αIR, the quark condensate ⟨q¯q⟩vac≠0 induces nine Nambu-Goldstone bosons: π,K,η, and a 0++ QCD dilaton σ. Physically, σ appears as the f0(500) resonance, a pole at a complex mass with real part ≲ mK. The ΔI=1/2 rule for nonleptonic K decays is then a consequence of χPTσ, with a KSσ coupling fixed by data for γγ→ππ and KS→γγ. We estimate RIR≈5 for the nonperturbative Drell-Yan ratio R=σ(e+e−→hadrons)/σ(e+e−→μ+μ−) at αIR and show that, in the many-color limit, σ/f0 becomes a narrow qq¯ state with planar-gluon corrections. Rules for the order of terms in χPTσ loop expansions are derived in Appendix A and extended in Appendix B to include inverse-power Li-Pagels singularities due to external operators. This relates to an observation that, for γγ channels, partial conservation of the dilatation current is not equivalent to σ-pole dominance.

Is "milk crust" a transient form of golden retriever ichthyosis?

BACKGROUND A recessive inherited form of lamellar ichthyosis is well recognized in golden retrievers. In this breed, young puppies demonstrate a self-limiting scaling disorder which is commonly recognized by breeders, who use the term "milk crust" to describe this syndrome. HYPOTHESIS/OBJECTIVES To determine whether "milk crust" is a new keratinization disorder or a self-limiting form of golden retriever ichthyosis. ANIMALS A total of 179 golden retriever dogs (21 dams and 158 puppies) were examined. METHODS Dermatological examination and assessment of the patatin-like phospholipase-1 (PNPLA1) genotype by PCR testing of buccal mucosal swabs. Skin biopsies from one affected puppy were evaluated for histopathological abnormalities. RESULTS Forty-five of 158 (28%) puppies exhibited scaling at 8 weeks of age; 113 of 158 (72%) were dermatologically normal. Of 144 analysed samples, 40 of 144 (28%) puppies demonstrated a homozygous mutation of the PNPLA1 genotype [of which, 36 of 40 (90%) had signs of scaling], 77 of 144 (53%) demonstrated a heterozygous mutation and 27 of 144 (19%) were a normal wild-type. In six of 17 (35%) dams, a homozygous mutation of the PNPLA1 genotype was found, eight of 17 (47%) demonstrated a heterozygous mutation and three of 17 (18%) were normal wild-type. Dams with a homozygous mutation were clinically unaffected. A 1 year follow-up revealed that 23 of 28 (82%) puppies affected with this syndrome failed to develop typical signs of ichthyosis. In five of 28 (18%) dogs there was persistence of mild scaling. CONCLUSIONS AND CLINICAL IMPORTANCE We hypothesize that the clinical syndrome termed "milk crust" could represent a transient form of golden retriever ichthyosis. Remission is not fully linked to PNPLA1 genotype, suggesting that unknown factors may contribute to the clinical disease.

Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II.

AIMS A non-invasive gene-expression profiling (GEP) test for rejection surveillance of heart transplant recipients originated in the USA. A European-based study, Cardiac Allograft Rejection Gene Expression Observational II Study (CARGO II), was conducted to further clinically validate the GEP test performance. METHODS AND RESULTS Blood samples for GEP testing (AlloMap(®), CareDx, Brisbane, CA, USA) were collected during post-transplant surveillance. The reference standard for rejection status was based on histopathology grading of tissue from endomyocardial biopsy. The area under the receiver operating characteristic curve (AUC-ROC), negative (NPVs), and positive predictive values (PPVs) for the GEP scores (range 0-39) were computed. Considering the GEP score of 34 as a cut-off (>6 months post-transplantation), 95.5% (381/399) of GEP tests were true negatives, 4.5% (18/399) were false negatives, 10.2% (6/59) were true positives, and 89.8% (53/59) were false positives. Based on 938 paired biopsies, the GEP test score AUC-ROC for distinguishing ≥3A rejection was 0.70 and 0.69 for ≥2-6 and >6 months post-transplantation, respectively. Depending on the chosen threshold score, the NPV and PPV range from 98.1 to 100% and 2.0 to 4.7%, respectively. CONCLUSION For ≥2-6 and >6 months post-transplantation, CARGO II GEP score performance (AUC-ROC = 0.70 and 0.69) is similar to the CARGO study results (AUC-ROC = 0.71 and 0.67). The low prevalence of ACR contributes to the high NPV and limited PPV of GEP testing. The choice of threshold score for practical use of GEP testing should consider overall clinical assessment of the patient's baseline risk for rejection.

An Avron rule for fragments of R-mingle

Axiomatic bases of admissible rules are obtained for fragments of the substructural logic R-mingle. In particular, it is shown that a ‘modus-ponens-like’ rule introduced by Arnon Avron forms a basis for the admissible rules of its implication and implication–fusion fragments, while a basis for the admissible rules of the full multiplicative fragment requires an additional countably infinite set of rules. Indeed, this latter case provides an example of a three-valued logic with a finitely axiomatizable consequence relation that has no finite basis for its admissible rules.

Regionalist Protest through Shared Rule? Peripherality and the Use of Cantonal Initiatives in Switzerland

In this article, we are interested in the extent to which federalism is able to deal with peripheral protest through shared rule channels. Shared rule as a key dimension of federal states has not thus far received adequate academic attention. Empirically, we analyse the use of all cantonal initiatives in Switzerland over the past 25 years as a particular instrument of shared rule, subsequently focusing on two peripheral regions with successful regionalist parties, Ticino and Geneva. We find that regionalist parties contribute towards radicalizing peripheral demands in search of attention from the centre. This leads to the mainstreaming of peripheral demands by pulling other parties along. We conclude that shared rule properly designed gives even the most peripheral regions a voice in national decisions, but that regionalist parties may also use shared rule instruments to mobilize their electorate at home to fight their non-regionalist competitors.