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Case identification is an ongoing issue for the COVID-19 epidemic, in particular for outpatient care where physicians must decide which patients to prioritise for further testing. This paper reports tools to classify patients based on symptom profiles based on 236 severe acute respiratory syndrome coronavirus 2 positive cases and 564 controls, accounting for the time course of illness using generalised multivariate logistic regression. Significant symptoms included abdominal pain, cough, diarrhoea, fever, headache, muscle ache, runny nose, sore throat, temperature between 37.5 and 37.9 °C and temperature above 38 °C, but their importance varied by day of illness at assessment. With a high percentile threshold for specificity at 0.95, the baseline model had reasonable sensitivity at 0.67. To further evaluate accuracy of model predictions, leave-one-out cross-validation confirmed high classification accuracy with an area under the receiver operating characteristic curve of 0.92. For the baseline model, sensitivity decreased to 0.56. External validation datasets reported similar result. Our study provides a tool to discern COVID-19 patients from controls using symptoms and day from illness onset with good predictive performance. It could be considered as a framework to complement laboratory testing in order to differentiate COVID-19 from other patients presenting with acute symptoms in outpatient care.
Inherited cholestasis of hepatocellular origin has long been described in the neonate or during the first year of life . Many of these infants were categorized as having idiopathic neonatal hepatitis after biliary atresia, metabolic diseases, and congenital infections were excluded . The prognosis in familial cholestasis was poor compared with sporadic cholestasis that sometimes had an identifiable etiology. As the clinical and genotypic heterogeneity of these inherited disorders has become apparent, it is now recognized that patients may present initially and progress to end-stage liver disease at ages ranging from infancy to adulthood [3, 4].There may be significant overlap in clinical features such as intense pruritus and a low serum concentration of gamma-glutamyltransferase (GGT). The histopathology, immunohistochemical staining, and hepatic ultrastructure may provide additional diagnostic clues as to the underlying defect. However, next generation sequencing including use of targeted gene panels has proven of great value in rapidly and reliably discriminating cholestatic diseases of childhood, may suggest therapy with varying success based on the genotype of the patient, and has advanced our understanding of molecular mechanisms of bile secretion and acquired cholestasis . It is not surprising that, so far, mutations in three genes encoding ATP-dependent transport proteins localized to the canalicular membrane that result in progressive cholestasis and liver injury have been discovered. The features of these disorders are compared in Table 13.1. Other genes encoding proteins involved in membrane transport, vesicular trafficking, and integrity of the cell junction may also be mutated in some patients. Mutations in the genes responsible for PFIC may be found in some adults with cryptogenic cholestasis and women with cholestasis of pregnancy including in the heterozygous state . Owing to an immaturity of hepatic excretory function, cholestasis may occasionally occur in inherited diseases because of systemic illness rather than a primary defect in the liver (see Table 9.1). These disorders will not be considered in this review.
The application of powder X-ray diffraction (PXRD) for the detection and quantification of low levels of a solid-state chemical impurity, BrettPhos oxide, in an active pharmaceutical ingredient is discussed. It is demonstrated that with appropriate methodology and experimentation, the impurity levels of as low as 0.07% w/w could be detected reliably and limit of quantification of 0.10% w/w could be achieved by PXRD, using a laboratory X-ray source. Method development, validation, and benchmarking using conventional high-performance liquid chromatography are presented in the manuscript highlighting the robustness and reproducibility of such measurements.
We report a 34-year-old male with a previously uninvestigated lifelong blindness of the right eye from compressive optic neuropathy secondary to congenital herniation of the gyrus rectus (HGR). His past medical history was otherwise unremarkable, with no history of prior head or ocular trauma. On examination, he had no light perception in the right eye, right relative afferent pupillary defect (RAPD), and primary optic atrophy. His left eye had normal visual acuity, color vision, and a healthy optic disc. There was a sensory exotropia in the right eye; however, extraocular movements were intact and the remainder of his neurological exam was normal. MRI revealed compression of the prechiasmatic right optic nerve from HGR and atrophy of the right optic nerve and optic chiasm (Figures 1 and 2), without any parenchymal mass lesions. There were no signal abnormalities in the optic nerves or the chiasm.
How does rhetoric work in the pursuit of political projects in international relations? This article analyzes how rhetoric-wielding political actors engage in reasoning to bolster their position by drawing upon norms that underwrite interactions, and audiences as scorekeepers evaluate the reasoning by making a series of inferences. I call this mechanism rhetorical reasoning. Building on the existing classification of norms in constructivist international relations (IR) and utilizing three distinct norm types – instrumental, institutional, and moral – I show the different processes through which political actors deploy rhetoric to legitimize and justify political projects and the distinct logics through which scorekeepers make inferences and evaluate the project. This article contributes to IR theories of argumentation by providing a sharp conceptualization of political rhetoric and actor–audience relationships in the game. I illustrate the mechanism of rhetorical reasoning using Brazil's UN peace enforcement operation in Haiti in 2004 to give empirical evidence for the role of institutional norm type in patterns of rhetorical reasoning and contestations in international politics. Paying attention to political rhetoric in the actor–scorekeepers' relationships in this way clarifies important issues regarding the varieties of political projects and the different role of normativity in the game.
Prenatal diagnosis and planned peri-partum care is an unexplored concept for care of neonates with critical CHDs in low-middle-income countries.
To report the impact of prenatal diagnosis on pre-operative status in neonates with critical CHD.
Prospective observational study (January 2017–June 2018) in tertiary paediatric cardiac facility in Kerala, India. Neonates (<28 days) with critical CHDs needing cardiac interventions were included. Pre-term infants (<35 weeks) and those without intention to treat were excluded. Patients were grouped into those with prenatal diagnosis and diagnosis after birth. Main outcome measure was pre-operative clinical status.
Total 119 neonates included; 39 (32.8%) had prenatal diagnosis. Eighty infants (67%) underwent surgery while 32 (27%) needed catheter-based interventions. Pre-operative status was significantly better in prenatal group; California modification of transport risk index of physiological stability (Ca-TRIPS) score: median 6 (0–42) versus 8 (0–64); p < 0.001; pre-operative assessment of cardiac and haemodynamic status (PRACHS) score: median 1 (0–4) versus 3 (0–10), p < 0.001. Age at cardiac procedure was earlier in prenatal group (median 5 (1–26) versus 7 (1–43) days; p = 0.02). Mortality occurred in 12 patients (10%), with 3 post-operative deaths (2.5%). Pre-operative mortality was higher in postnatal group (10% versus 2.6%; p = 0.2) of which seven (6%) died due to suboptimal pre-operative status precluding surgery.
Prenatal diagnosis and planned peri-partum care had a significant impact on the pre-operative status in neonates with critical CHD in a low-resource setting.
A 59-year-old man presented with confusion, decreased level of consciousness, and generalized tonic–clonic seizures. He was intubated and promptly stabilized on antiepileptic medications. He was not in status epilepticus. He improved after seizure control, though he remained confused. He was neither acutely intoxicated nor were there any substance withdrawal concerns prior to his presentation. Furthermore, no metabolic, electrolyte, or nutritional perturbations were identified. He did, however, have a history of alcoholic hepatitis and was awaiting a liver transplant, but his blood work did not reveal evidence of fulminant hepatic failure at presentation (international normalized ratio – 1.17, platelet count 161,000/µL, ammonia 18 µmol/L, blood urea nitrogen 4.5 mmol/L, and his liver enzymes were only remarkable for an elevated alkaline phosphatase of 143 U/L).
Of the ten fastest growing economies since 1960, eight
are in East Asia. As Haggard (2018) aptly
demonstrates for Northeast Asia, two explanations
account for this exceptional regional performance.
On the one hand, neo-liberals committed to an
Anglo-American night-watchman state (Krueger 1978;
Bhagwati 1978; Edwards 1993; World Bank 1993; Pack
and Saggi 2006) attribute performance to
macroeconomic stability, provision of public goods,
and openness to trade and investment. On the other
hand, a heterodox group (Johnson 1982; Amsden 1989;
Wade 1990/2004; Chang 2002, 1994; Rodrik 1995; Evans
1995; Lin 2009) focuses on market and coordination
failures and the need for states to adopt pragmatic,
‘trial and error’ and selective approaches to
high-speed growth. In this latter view, the strong
developmental states of Northeast Asia used their
embedded autonomy viz the private sector to overcome
market and coordination failures to usher in rapid
growth and technological catch-up.