Use of ROC curve analysis for prediction gives fallacious results: Use predictivity-based indices.

ABSTRACT: The area under the ROC curve is frequently used for assessing the predictive efficacy of a model, and the Youden index is commonly used to provide the optimal cut-off. Both are misleading tools for predictions. A ROC curve is drawn for the sensitivity of a quantitative test against its (1 - specificity) at different values of the test. Both sensitivity and specificity are retrospective in nature as these are indicators of correct classification of already known conditions. They are not indicators of future events and are not valid for predictions. Predictivity intimately depends on the prevalence which may be ignored by sensitivity and specificity. We explain this fallacy in detail and illustrate with several examples that the actual predictivity could differ greatly from the ROC curve-based predictivity reported by many authors. The predictive efficacy of a test or a model is best assessed by the percentage correctly predicted in a prospective framework. We propose predictivity-based ROC curves as tools for providing predictivities at varying prevalence in different populations. For optimal cut-off for prediction, in place of the Youden index, we propose a P-index where the sum of positive and negative predictivities is maximum after subtracting 1. To conclude, for correctly assessing adequacy of a prediction models, predictivity-based ROC curves should be used instead of the usual sensitivity-specificity-based ROC curves and the P-index should replace the Youden index.

Individual perceptions of community efficacy for non-communicable disease management in twelve communities in China: cross-sectional and longitudinal analyses.

OBJECTIVES: This objective of this study was to use empirical data to assess cross-sectional variation singular and changes over time in community efficacy for non-communicable diseases (NCDs) management (COEN) and to examine individual factors associated with changes in COEN. STUDY DESIGN: This was a longitudinal observational study. METHODS: Participants with hypertension and diabetes were randomly selected from 12 communities from three cities in eastern China, and a baseline survey and a 1-year follow-up were conducted. The COEN scale has five dimensions: community physical environment (CPE), behavioral risk factors (BRF), mental health and social relationships (MHSR), community health management (CHM), and community organisations and activities (COA). Mixed-effects models were used to investigate the change in COEN over time and the association between individual factors and changes in COEN. RESULTS: COEN scores showed significant variation singular among the 12 communities (P < 0.001) at the baseline. In the mixed-effects model, CPE (ß coefficient: 1.62, P < 0.001), BRF (0.90, P < 0.001), MHSR (0.86, P < 0.001), CHM (0.46, P < 0.001), and total scores (ß = 3.57, P < 0.001) increased significantly over time. The changes in COEN were associated with individual characteristics (e.g., older, men, more educated). CONCLUSIONS: Cross-sectional variations and changes over time in COEN demonstrated the utility of a sensitive instrument. Factors such as age, gender, marriage, education level, and employment may affect the financial and social resources assignment for NCD management. Our findings suggest that further high-quality studies are needed to better evaluate the effect of community empowerment on the prevention and control of NCDs.

Sustainable multi-trait selection index based on production, reproduction, and health traits for genetic improvement of Murrah buffaloes.

Selection of Murrah buffaloes based on production, reproduction, and health traits play an important role in sustainable genetic improvement. With the aim to construct an index comprising of production, reproduction and health traits of Murrah buffaloes, the production and reproduction data during a 50-year span (1971-2020) and for health traits data of 27 years (1994-2020) were analyzed. Various three, four, five, and six trait combinations of production, reproduction, and health traits were explored for construction of performance indices. The income and expenditure method was used to calculate relative economic values (REV) for traits under consideration. A total of 37 performance indices were constructed using a multi-trait combination of production, reproduction, and health traits. Out of 37 indices, the (ADMY-PY-DO-AFC-FF) based index was identified as the best, with 78%, 2%, and 20% weightage given to production, reproduction, and female fertility, respectively. Furthermore, when REVs of traits were increased by 25% and 50%, there was no change observed in the relative importance of traits in the best index, indicating that the index was robust to substantial increases in economic values. Therefore, it is recommended that the above constructed composite selection index can be employed in selection of female buffaloes to achieve sustainable genetic gain.

Clinico-radiological findings of neuroendocrine tumour metastases to the orbit.

PURPOSE: We present the clinico-radiological findings of neuroendocrine tumour metastases to the orbit. METHODS: This was a multicentre, retrospective study of patients with neuroendocrine tumour metastases to the orbit. Data was collected from medical records across five different sites within Australia and the United Kingdom. RESULTS: Nine patients (eleven lesions) were identified. The most common presenting complaint was diplopia (5/9, 56%). Disease occurred bilaterally in two patients. Seven patients (78%) had extraocular muscle involvement. The lateral recti (4/9, 44%) and superior recti (2/9, 22%) were the most commonly affected. Ocular presentation preceded primary tumour diagnosis in three patients (33%). On orbital imaging, metastases were most commonly reported as well circumscribed, ovoid or round, heterogeneous, contrast-enhancing masses. Features of intralesional haemorrhage and bony invasion are uncommonly reported. CONCLUSIONS: Neuroendocrine tumour metastasis to the orbit is uncommon. Metastases have a propensity for the extraocular muscles, commonly presenting as heterogeneous, well circumscribed, contrast-enhancing lesions on neuroimaging. New ocular symptoms, a history of neuroendocrine tumours, and these radiological findings, should lead to high clinical suspicion of metastatic disease. Atypical findings warrant biopsy to exclude other causes of orbital lesions.

A unique case of light chain (AL) amyloidosis masquerading as hypophosphatemic osteomalacia.

Light chain (AL) amyloidosis is the result of a clonal plasma cell disorder which causes organ damage by deposition of misfolded light chains. Kidney is a common site of amyloid deposition. Proteinuria, usually in nephrotic range and unexplained renal insufficiency are the main manifestations of renal injury. We report a unique case of renal involvement by AL amyloidosis masquerading as metabolic bone disease. 38 year old male patient presented with progressively increasing diffuse bony pains, low backache and proximal weakness of both lower limbs since two years. On investigation, he was detected to have hypophosphatemic osteomalacia due to renal phosphate loss which was fibroblast growth factor 23 (FGF23)- independent. He also had nephrotic range low molecular weight proteinuria. Renal biopsy to ascertain the aetiology revealed deposition of amyloid fibrils in the glomerular mesangium on electron microscopy. Its characterization by immunofluorescence (IF) was consistent with immunoglobulin light chain (AL) amyloidosis. In the absence of a demonstrable plasma cell clone on bone marrow biopsy, we made a diagnosis of monoclonal gammopathy of renal significance (MGRS). He was treated with chemotherapy following which there was symptomatic improvement and reduction in phosphaturia. This case describes a unique presentation of renal injury due to AL amyloidosis masquerading as hypophosphatemic osteomalacia. The aim of this report is to highlight that hypophosphatemia in adults is usually acquired and treatment of underlying etiology results in cure, unlike in children where genetic counseling and phosphate replacement is the mainstay of treatment.

Validation of Complete Hindi Version of Douleur Neuropathique 4 Questionnaire for Assessment of Neuropathic Pain.

OBJECTIVES: The Douleur Neuropathique 4 (DN4) questionnaire is a widely used tool for the diagnosis of neuropathic pain (NP). The aim was to validate the Complete Hindi version of DN4 (CH-DN4) questionnaire. MATERIALS AND METHODS: A systematic translation process was used to translate the original English DN4 into Hindi. The Hindi version was validated among patients appearing in the pain clinic of a tertiary hospital in the capital of Delhi by two different raters. We assessed the internal consistency, test-retest reliability, and inter-rater agreement, validity, sensitivity, specificity, positive and negative predictive values, and area under the curve (AUC). RESULTS: A total of 285 participants, out of which 153 had NP and 132 had non NP (NNP) were included in the study. The results showed our CH-DN4 to have good diagnostic accuracy, a score of ≥ 3.5 was found to be the best cut-off for the diagnosis of NP, with a sensitivity of 0.78, specificity of 0.76, a positive predictive value of 78.5%, and a negative predictive value of 74.5%. Cronbach's α was 0.82 (95% confidence interval: 0.80-0.84), and interclass correlation coefficients was 0.95. The AUC was >0.8 indicating excellent discrimination between NP and NNP. CONCLUSION: The CH-DN4 questionnaire has been found to be a reliable and valid screening tool with an excellent power to discriminate between NP and NNP.

Management of congenital ichthyoses: European guidelines of care, part two.

These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016, and a consensus on the discussions. These guidelines summarize evidence and expert-based recommendations and intend to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part two, covering the management of complications and the particularities of some forms of congenital ichthyosis.

Management of congenital ichthyoses: European guidelines of care, part one.

These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert-based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling.

A randomised controlled trial of phenylephrine and noradrenaline boluses for treatment of postspinal hypotension during elective caesarean section.

Phenylephrine is currently the vasopressor of choice during elective caesarean section, but it can cause reflex bradycardia. Noradrenaline, a potent α-agonist and weak ß-agonist, may be associated with a lower incidence of bradycardia. However, comparative information is limited. This double-blind randomised controlled trial compared the effects of 100 µg phenylephrine and 5 µg noradrenaline administered as boluses for the treatment of postspinal hypotension during elective caesarean section in women with an uncomplicated singleton pregnancy. Hypotension was defined as a decrease of ≥ 20% from baseline systolic arterial pressure, or an absolute value < 100 mmHg. Ninety women were included in the study. The primary outcome was the incidence of maternal bradycardia < 60 beats.min-1 . There was no difference in the incidence of bradycardia (37.8% with phenylephrine vs. 22.2% with noradrenaline; p = 0.167), number of hypotensive episodes, number of boluses required to treat the first hypotensive episode or reactive hypertension. The total number of boluses used was higher in the phenylephrine group (p = 0.01). Maternal heart rate at 1 min after vasopressor administration was non-significantly lower using phenylephrine vs. noradrenaline (p = 0.034, considering p < 0.01 as statistically significant). The umbilical artery pH was higher using phenylephrine than with noradrenaline (p = 0.034). In conclusion, both vasopressors reversed postspinal hypotension without a statistically significant difference in maternal bradycardia. However, in view of the lower umbilical artery pH when using noradrenaline, further research is warranted to study its placental transfer and fetal metabolic effects.

Nanoscale-shape-mediated coupling between temperature and densification in intense pulsed light sintering.

In intense pulsed light sintering (IPL), pulsed large-area visible light from a xenon lamp is absorbed by nanoparticle films or patterns and converted to heat, resulting in rapid sintering of the nanoparticles. This work experimentally characterizes IPL of silver nanoparticle films. A newly observed turning point in the evolution of film temperature during IPL is correlated to the observation, in literature and in this work, that film densification levels off beyond a critical pulse fluence and number of pulses. A computational model is developed that couples electromagnetic finite element analysis, heat transfer models and densification models to predict the evolution of film temperature and density during IPL. This model is able to capture the experimentally observed turning point in temperature during IPL, whereas current models of IPL are unable to do so. It is shown that the temperature turning point occurs due to a coupling between optical absorption and densification in the nanoparticle film, mediated by a change in nanoscale shape of the deposited nanoparticles due to interparticle neck growth. Further, it is found that the optical fluence per pulse has a greater effect on the achievable film density in IPL, as compared to the number of pulses.

Higher protein intake is associated with increased risk for incident end-stage renal disease among blacks with diabetes in the Southern Community Cohort Study.

BACKGROUND AND AIMS: Diabetes, a risk factor for end-stage renal disease (ESRD), is associated with impaired protein metabolism. We investigated whether protein intake is associated with ESRD and whether the risk is higher among blacks with diabetes. METHODS AND RESULTS: We conducted a nested case-control study of ESRD within the Southern Community Cohort Study, a prospective study of low-income blacks and whites in the southeastern US (2002-2009). Through 2012, 1057 incident ESRD cases were identified by linkage with the United States Renal Data System and matched to 3198 controls by age, sex, and race. Dietary intakes were assessed from a validated food frequency questionnaire at baseline. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models that included matching variables, BMI, education, income, hypertension, total energy intake, and percent energy from saturated and polyunsaturated fatty acids. Mean (±SD) daily energy intake from protein was higher among ESRD cases than controls (15.7 ± 3.3 vs. 15.1 ± 3.1%, P < 0.0001). For a 1% increase in percent energy intake from protein, the adjusted ORs (95% CIs) for ESRD were 1.06 (1.02-1.10) for blacks with diabetes, 1.02 (0.98-1.06) for blacks without diabetes, 0.99 (0.90-1.09) for whites with diabetes and 0.94 (0.84-1.06) for whites without diabetes. Protein intake in g/kg/day was also associated with ESRD (4th vs. 1st quartile OR = 1.76; 95% CI: 1.17-2.65). CONCLUSION: Our results raise the possibility that among blacks with diabetes, increased dietary protein is associated with increased incidence of ESRD. Studies on how protein intake and metabolism affect ESRD are needed.

Ocular disability--WHO grade 2 in persons affected with leprosy.

Leprosy remains to be a leading cause of peripheral neuropathy and disability. In recent years under Leprosy control programme more stress is being laid on disability assessment. This study was aimed to find prevalence of grade of Ocular disability among persons affected with leprosy (PAL) according to WHO disability grading scale and to find Ocular contributors to grade 2 disability in PAL. A cross sectional study was carried out in tertiary care hospital in Lucknow, Uttar Pradesh. About 302 PAL were interviewed and their eyes clinically examined during 2 years. Data was analysed in percentages, x2 test, Anova. Ocular disability was found in 39.40% persons affected with leprosy (PAL). Of 604 eyes, 13.07% had grade 1 disability and 19.86% had grade 2 disabilities. Bilateral disability was more common than unilateral disability. Ocular disability was more common in PAL with more than one year of leprosy and even higher in those staying in leprasoria (p = 0.012). The most common cause of ocular grade 2 disabilities was corneal involvement (14.23% PAL). Cataract was found to be the most common cause of visual disability (although it is not caused by leprosy). Screening for ocular disability should be incorporated as a routine protocol in PAL to reduce the severity of Ocular disability. Early diagnosis and prompt preventive measure is essential to reduce the burden of visual impairment and blindness in PALthus bringing down the load of grade 2 disability due to leprosy in the society which in itself is an indicator of leprosy control.

The minimum effective dose (ED90) of prophylactic oxytocin infusion during cesarean delivery in patients with and without obesity: an up-down sequential allocation dose-response study.

BACKGROUND: Obesity is associated with greater oxytocin requirement during labor induction or augmentation. There are scant data exploring the intra-operative requirement during cesarean delivery in patients with obesity, and none comparing it with those without obesity. We evaluated the minimum effective dose (ED90) of an oxytocin infusion to achieve adequate uterine tone during cesarean delivery in patients with and without obesity. METHODS: Patients (body mass index ≥30 kg/m2 represented patients with obesity) undergoing cesarean delivery using subarachnoid block were included. This prospective dual-arm dose-finding study used a 9:1 biased sequential allocation design. Oxytocin infusion was initiated at 13 IU/h at cord clamping in the first patient of each group. Uterine tone was graded as satisfactory or unsatisfactory by the obstetrician four minutes after initiation of the infusion. The dose of oxytocin infusion for subsequent patients was determined according to the response of the previous patient in the group. Oxytocin-associated side effects were evaluated. Dose-response data for the groups was evaluated using log-logistic function and ED90 estimates derived from fitted equations using the delta method. RESULTS: The ED90 of oxytocin was significantly higher for patients with obesity (n = 40) compared with those without obesity (n = 40) [25.7 IU/h, 95% CI 18.6 to 32.9) vs. 16.6 IU/h, 95% CI 14.9 to 18.3)]; relative ratio 1.55 [95% CI 1.09 to 2.01] (P = 0.019). CONCLUSIONS: Patients with obesity require a higher intra-operative oxytocin infusion dose rate to achieve a satisfactorily contracted uterus after fetal delivery when compared with patients without obesity.

Onboarding of siponimod in secondary progressive multiple sclerosis patients in Australia: Novel, real-world evidence from the MSGo digital support programme.

Background: Siponimod is approved for use in people with secondary progressive multiple sclerosis (pwSPMS). An integrated digital platform, MSGo, was developed for pwSPMS and clinicians to help navigate the multiple steps of the pre-siponimod work-up. Objective: To explore real-world onboarding experiences of siponimod amongst pwSPMS in Australia. Methods: Retrospective, non-interventional, longitudinal, secondary analysis of data extracted from MSGo (20 April 2022). The primary endpoint was the average time for siponimod onboarding; secondary endpoints were adherence and sub-group analyses of variables influencing onboarding. Results: Mixed-cure modelling estimated that 58% of participants (N = 368, females 71%, median age of 59 years) registered in MSGo would ever initiate siponimod. The median time to initiation was 56 days (95% CI [47-59] days). Half of the participants cited 'waiting for vaccination' as the reason for initiation delay. Cox regression analyses found participants with a nominated care partner had faster onboarding (HR 2.1, 95% CI [1.5-3.0]) and were more likely to continue self-reporting daily siponimod dosing than were those without a care partner (HR 2.2, 95% CI [1.3-3.7]). Conclusions: Despite the limitations of self-reported data and the challenges of the COVID-19 pandemic, this study provides insights into siponimod onboarding in Australia and demonstrates the positive impact of care partner support.

The effect of the home environment on physical activity and dietary intake in preschool children.

BACKGROUND: The effects of the home environment on child health behaviors related to obesity are unclear. PURPOSE: To examine the role of the home physical activity (PA) and food environment on corresponding outcomes in young children, and assess maternal education/work status as a moderator. METHODS: Overweight or obese mothers reported on the home PA and food environment (accessibility, role modeling and parental policies). Outcomes included child moderate-vigorous PA (MVPA) and sedentary time derived from accelerometer data and two dietary factors ('junk' and healthy food intake scores) based on factor analysis of mother-reported food intake. Linear regression models assessed the net effect (controlling for child demographics, study arm, supplemental time point, maternal education/work status, child body mass index and accelerometer wear time (for PA outcomes)) of the home environment on the outcomes and moderation by maternal education/work status. Data were collected in North Carolina from 2007 to 2011. RESULTS: Parental policies supporting PA increased MVPA time, and limiting access to unhealthy foods increased the healthy food intake score. Role modeling of healthy eating behaviors increased the healthy food intake score among children of mothers with no college education. Among children of mothers with no college education and not working, limiting access to unhealthy foods and role modeling reduced 'junk' food intake scores whereas parental policies supporting family meals increased 'junk' food intake scores. CONCLUSIONS: To promote MVPA, parental policies supporting child PA are warranted. Limited access to unhealthy foods and role modeling of healthy eating may improve the quality of the child's food intake.

Lack of activity of 15-epi-lipoxin A4 on FPR2/ALX and CysLT1 receptors in interleukin-8-driven human neutrophil function.

Neutrophil recruitment and survival are important control points in the development and resolution of inflammatory processes. 15-epi-lipoxin (LX)A interaction with formyl peptide receptor 2 (FPR2)/ALX receptor is suggested to enhance anti-inflammatory neutrophil functions and mediate resolution of airway inflammation. However, it has been reported that 15-epi-LXA4 analogues can also bind to cysteinyl leukotriene receptor 1 (CysLT1) and that the CysLT1 antagonist MK-571 binds to FPR2/ALX, so cross-reactivity between FPR2/ALX and CysLT1 ligands cannot be discarded. It is not well established whether the resolution properties reported for 15-epi-LXA4 are mediated through FPR2/ALX, or if other receptors such as CysLT1 may also be involved. Evaluation of specific FPR2/ALX ligands and CysLT1 antagonists in functional biochemical and cellular assays were performed to establish a role for both receptors in 15-epi-LXA4-mediated signalling and function. In our study, a FPR2/ALX synthetic peptide (WKYMVm) and a small molecule FPR2/ALX agonist (compound 43) induced FPR2/ALX-mediated signalling, enhancing guanosine triphosphate-gamma (GTPγ) binding and decreasing cyclic adenosine monophosphate (cAMP) levels, whereas 15-epi-LXA4 was inactive. Furthermore, 15-epi-LXA4 showed neither binding affinity nor signalling towards CysLT1. In neutrophils, 15-epi-LXA4 showed a moderate reduction of interleukin (IL)-8-mediated neutrophil chemotaxis but no effect on neutrophil survival was observed. In addition, CysLT1 antagonists were inactive in FPR2/ALX signalling or neutrophil assays. In conclusion, 15-epi-LXA4 is not a functional agonist or an antagonist of FPR2/ALX or CysLT1, shows no effect on IL-8-induced neutrophil survival and produces only moderate inhibition in IL-8-mediated neutrophil migration. Our data do not support an anti-inflammatory role of 15-epi-LXA4- FPR2/ALX interaction in IL-8-induced neutrophil inflammation.

Multi-environment QTL analyses for drought-related traits in a recombinant inbred population of chickpea (Cicer arietinum L.).

A recombinant inbred line (RIL) population, comprising 181 lines derived from ILC588 × ILC3279, was evaluated in 10 environments across three locations with different moisture gradients. A drought resistance score (DRS) and three phenology traits-plant height (PLHT), days to flowering (DFLR), and days to maturity (MAT)-were recorded along with seven yield-related traits-grain yield (GY), biological yield (BY), harvest index (HI), the number of pods/3 plants (Pod), percentage of empty pods (%Epod), 100 seed weight (100 sw), and seed number/3 plants (SN). Two RILs (152, 162) showed the best GYs and DRSs under stressed and non-stressed environments. The quantitative trait loci (QTLs) analyses detected 93 significant QTLs (LOD ≥ 2.0) across the genome × environment interactions. The highest phenotypic variation (>24 %) was explained by the QTLDFLR in Terbol-11. Four common possible pleiotropic QTLs on LG3 and LG4 were identified as associated with DFLR, DRS, GY, MAT, HI, SN, and Pod. No significant epistatic interactions were found between these QTLs and the other markers. However, the QTL for DRS was detected as a conserved QTL in three late planting environments. The markers H6C-07 (on LG3) and H5G01 (on LG4) were associated with QTLs for many traits in all environments studied except two. The allele 'A' of marker H6C07 (from the tolerant parent ILC588) explained 80 % of the yield increase under late planting and 29.8 % of that under dry environments. Concentrating on LG3 and LG4 in molecular breeding programs for drought could speed up improvement for these traits.

Acquired lacrimal sac fistula mimicking basal cell carcinoma.

BACKGROUND: Lacrimal sac fistulae can arise after an episode of dacryocystitis, usually forming below the medial canthus. Preceding symptoms of a watery eye with mucous discharge and a history or signs of inflammation are typical. OBJECTIVES: To highlight the features of lacrimal sac fistulae and encourage readers to consider this in the differential diagnosis of apparently ulcerative medial canthal skin lesions. METHODS: We describe three patients with inferior-medial canthal ulcerative skin lesions, all referred to ophthalmic plastic surgeons either by dermatologists or plastic surgeons, presumed clinically to have basal cell carcinoma (BCC). RESULTS: All three were in fact due to acquired lacrimal sac fistulae, and syringing of the nasolacrimal system confirmed the presence of a fistula. CONCLUSIONS: These cases illustrate the importance of questioning patients about their previous ocular symptoms when dealing with less familiar periocular lesions.

Environment-friendly route for stable aqueous dispersion of reduced graphene oxide for heat transfer application.

A simultaneous functionalization and reduction route to prepare stable dispersion of reduced graphene oxide from graphene oxide has been described. Diethanol amine has been introduced for the first time as an environment friendly reducing agent in a simple reflux reaction. Diethanol amine acts as a reducing agent and helps to enhance the stability of dispersion, making hydrogen bonding by virtue of two functional groups. The prepared dispersion of 0.025 mg/mL concentration is stable for months together and has a zeta potential value -45 V at room temperature. UV-Vis study shows peak at 264 nm that is signatory for reduced graphene oxide. TEM images confirm spread thin sheets of graphene of few hundred nanometer lateral dimension. Thermal diffusivity studies suggest nearly 60% enhancement for the dispersion in comparison to base fluid, water. This suggests graphene dispersion is promising for heat transfer applications.