Robust PCA and MIC statistics of baryons in early minihaloes

We present a novel approach, based on robust principal components analysis (RPCA) and maximal information coefficient (MIC), to study the redshift dependence of halo baryonic properties. Our data are composed of a set of different physical quantities for primordial minihaloes: dark matter mass (M-dm), gas mass (M-gas), stellar mass (M-star), molecular fraction (x(mol)), metallicity (Z), star formation rate (SFR) and temperature. We find that M-dm and M-gas are dominant factors for variance, particularly at high redshift. Nonetheless, with the emergence of the first stars and subsequent feedback mechanisms, x(mol), SFR and Z start to have a more dominant role. Standard PCA gives three principal components (PCs) capable to explain more than 97 per cent of the data variance at any redshift (two PCs usually accounting for no less than 92 per cent), whilst the first PC from the RPCA analysis explains no less than 84 per cent of the total variance in the entire redshift range (with two PCs explaining greater than or similar to 95 per cent anytime). Our analysis also suggests that all the gaseous properties have a stronger correlation with M-gas than with M-dm, while M-gas has a deeper correlation with x(mol) than with Z or SFR. This indicates the crucial role of gas molecular content to initiate star formation and consequent metal pollution from Population III and Population II/I regimes in primordial galaxies. Finally, a comparison between MIC and Spearman correlation coefficient shows that the former is a more reliable indicator when halo properties are weakly correlated

The Overlooked Potential of Generalized Linear Models in Astronomy - I: Binomial Regression

Revealing hidden patterns in astronomical data is often the path to fundamental scientific breakthroughs; meanwhile the complexity of scientific inquiry increases as more subtle relationships are sought. Contemporary data analysis problems often elude the capabilities of classical statistical techniques, suggesting the use of cutting edge statistical methods. In this light, astronomers have overlooked a whole family of statistical techniques for exploratory data analysis and robust regression, the so-called Generalized Linear Models (GLMs). In this paper -- the first in a series aimed at illustrating the power of these methods in astronomical applications -- we elucidate the potential of a particular class of GLMs for handling binary/binomial data, the so-called logit and probit regression techniques, from both a maximum likelihood and a Bayesian perspective. As a case in point, we present the use of these GLMs to explore the conditions of star formation activity and metal enrichment in primordial minihaloes from cosmological hydro-simulations including detailed chemistry, gas physics, and stellar feedback. We predict that for a dark mini-halo with metallicity $\approx 1.3 \times 10^{-4} Z_{\bigodot}$, an increase of $1.2 \times 10^{-2}$ in the gas molecular fraction, increases the probability of star formation occurrence by a factor of 75%. Finally, we highlight the use of receiver operating characteristic curves as a diagnostic for binary classifiers, and ultimately we use these to demonstrate the competitive predictive performance of GLMs against the popular technique of artificial neural networks.Comment: 20 pages, 10 figures, 3 tables, accepted for publication in Astronomy and Computin

Homologous Recombination Deficiency in Ovarian Cancer: from the Biological Rationale to Current Diagnostic Approaches

The inability to efficiently repair DNA double-strand breaks using the homologous recombination repair pathway is defined as homologous recombination deficiency (HRD). This molecular phenotype represents a positive predictive biomarker for the clinical use of poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors and platinum-based chemotherapy in ovarian cancers. However, HRD is a complex genomic signature, and different methods of analysis have been developed to introduce HRD testing in the clinical setting. This review describes the technical aspects and challenges related to HRD testing in ovarian cancer and outlines the potential pitfalls and challenges that can be encountered in HRD diagnostics

123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography and 123I-metaiodobenzylguanidine myocardial scintigraphy in differentiating dementia with lewy bodies from other dementias: A comparative study

Objective: To compare the diagnostic value of striatal 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) single photon emission computed tomography (SPECT) and 123I-metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types. Methods: This prospective longitudinal study included 30 patients with a clinical diagnosis of DLB and 29 patients with non-DLB dementia (Alzheimer disease, n = 16; behavioral variant frontotemporal dementia, n = 13). All patients underwent 123I-FP-CIT SPECT and 123I-MIBG myocardial scintigraphy within a few weeks of clinical diagnosis. All diagnoses at each center were agreed upon by the local clinician and an independent expert, both unaware of imaging data, and re-evaluated after 12 months. Each image was visually classified as either normal or abnormal by 3 independent nuclear physicians blinded to patients' clinical data. Results: Overall, sensitivity and specificity to DLB were respectively 93% and 100% for 123I-MIBG myocardial scintigraphy, and 90% and 76% for 123I-FP-CIT SPECT. Lower specificity of striatal compared to myocardial imaging was due to decreased 123I-FP-CIT uptake in 7 non-DLB subjects (3 with concomitant parkinsonism) who had normal 123I-MIBG myocardial uptake. Notably, in our non-DLB group, myocardial imaging gave no false-positive readings even in those subjects (n = 7) with concurrent medical illnesses (diabetes and/or heart disease) supposed to potentially interfere with 123I-MIBG uptake. Interpretation: 123I-FP-CIT SPECT and 123I-MIBG myocardial scintigraphy have similar sensitivity for detecting DLB, but the latter appears to be more specific for excluding non-DLB dementias, especially when parkinsonism is the only “core feature” exhibited by the patient. Our data also indicate that the potential confounding effects of diabetes and heart disease on 123I-MIBG myocardial scintigraphy results might have been overestimated. Ann Neurol 2016;80:368–378

A systematic review on the performance of fracture risk assessment tools: FRAX, DeFRA, FRA-HS

Purpose: Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients. Methods: PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59–88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men. Conclusion: The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools

The integrated structure of care: evidence for the efficacy of models of clinical governance in the prevention of fragility fractures after recent sentinel fracture after the age of 50 years

Summary : Randomized clinical trials and observational studies on the implementation of clinical governance models, in patients who had experienced a fragility fracture, were examined. Literature was systematically reviewed and summarized by a panel of experts who formulated recommendations for the Italian guideline. Purpose: After experiencing a fracture, several strategies may be adopted to reduce the risk of recurrent fragility fractures and associated morbidity and mortality. Clinical governance models, such as the fracture liaison service (FLS), have been introduced for the identification, treatment, and monitoring of patients with secondary fragility fractures. A systematic review was conducted to evaluate the association between multidisciplinary care systems and several outcomes in patients with a fragility fracture in the context of the development of the Italian Guidelines. Methods: PubMed, Embase, and the Cochrane Library were investigated up to December 2020 to update the search of the Scottish Intercollegiate Guidelines Network. Randomized clinical trials (RCTs) and observational studies that analyzed clinical governance models in patients who had experienced a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random-effects models. Primary outcomes were bone mineral density values, antiosteoporotic therapy initiation, adherence to antiosteoporotic medications, subsequent fracture, and mortality risk, while secondary outcomes were quality of life and physical performance. Results: Fifteen RCTs and 62 observational studies, ranging from very low to low quality for bone mineral density values, antiosteoporotic initiation, adherence to antiosteoporotic medications, subsequent fracture, mortality, met our inclusion criteria. The implementation of clinical governance models compared to their pre-implementation or standard care/non-attenders significantly improved BMD testing rate, and increased the number of patients who initiated antiosteoporotic therapy and enhanced their adherence to the medications. Moreover, the treatment by clinical governance model respect to standard care/non-attenders significantly reduced the risk of subsequent fracture and mortality. The integrated structure of care enhanced the quality of life and physical function among patients with fragility fractures. Conclusions: Based on our findings, clinicians should promote the management of patients experiencing a fragility fracture through structured and integrated models of care. The task force has formulated appropriate recommendations on the implementation of multidisciplinary care systems in patients with, or at risk of, fragility fractures

Executive summary: Italian guidelines for diagnosis, risk stratification, and care continuity of fragility fractures 2021

Background: Fragility fractures are a major public health concern owing to their worrying and growing burden and their onerous burden upon health systems. There is now a substantial body of evidence that individuals who have already suffered a fragility fracture are at a greater risk for further fractures, thus suggesting the potential for secondary prevention in this field. Purpose: This guideline aims to provide evidence-based recommendations for recognizing, stratifying the risk, treating, and managing patients with fragility fracture. This is a summary version of the full Italian guideline. Methods: The Italian Fragility Fracture Team appointed by the Italian National Health Institute was employed from January 2020 to February 2021 to (i) identify previously published systematic reviews and guidelines on the field, (ii) formulate relevant clinical questions, (iii) systematically review literature and summarize evidence, (iv) draft the Evidence to Decision Framework, and (v) formulate recommendations. Results: Overall, 351 original papers were included in our systematic review to answer six clinical questions. Recommendations were categorized into issues concerning (i) frailty recognition as the cause of bone fracture, (ii) (re)fracture risk assessment, for prioritizing interventions, and (iii) treatment and management of patients experiencing fragility fractures. Six recommendations were overall developed, of which one, four, and one were of high, moderate, and low quality, respectively. Conclusions: The current guidelines provide guidance to support individualized management of patients experiencing non-traumatic bone fracture to benefit from secondary prevention of (re)fracture. Although our recommendations are based on the best available evidence, questionable quality evidence is still available for some relevant clinical questions, so future research has the potential to reduce uncertainty about the effects of intervention and the reasons for doing so at a reasonable cost

Refracture following vertebral fragility fracture when bone fragility is not recognized: summarizing findings from comparator arms of randomized clinical trials

Purpose: Since vertebral fragility fractures (VFFs) might increase the risk of subsequent fractures, we evaluated the incidence rate and the refracture risk of subsequent vertebral and non-vertebral fragility fractures (nVFFs) in untreated patients with a previous VFF. Methods: We systematically searched PubMed, Embase, and Cochrane Library up to February 2022 for randomized clinical trials (RCTs) that analyzed the occurrence of subsequent fractures in untreated patients with prior VFFs. Two authors independently extracted data and appraised the risk of bias in the selected studies. Primary outcomes were subsequent VFFs, while secondary outcomes were further nVFFs. The outcome of refracture within ≥ 2 years after the index fracture was measured as (i) rate, expressed per 100 person-years (PYs), and (ii) risk, expressed in percentage. Results: Forty RCTs met our inclusion criteria, ranging from medium to high quality. Among untreated patients with prior VFFs, the rate of subsequent VFFs and nVFFs was 12 [95% confidence interval (CI) 9-16] and 6 (95% CI 5-8%) per 100 PYs, respectively. The higher the number of previous VFFs, the higher the incidence. Moreover, the risk of VFFs and nVFFs increased within 2 (16.6% and 8%) and 4 years (35.1% and 17.4%) based on the index VFF. Conclusion: The highest risk of subsequent VFFs or nVFFs was already detected within 2 years following the initial VFF. Thus, prompt interventions should be designed to improve the detection and treatment of VFFs, aiming to reduce the risk of future FFs and properly implement secondary preventive measures

Medication holidays in osteoporosis: evidence-based recommendations from the Italian guidelines on ‘Diagnosis, risk stratification, and continuity of care of fragility fractures’ based on a systematic literature review

Background: Noncommunicable, chronic diseases need pharmacological interventions for long periods or even throughout life. The temporary or permanent cessation of medication for a specific period, known as a ‘medication holiday,’ should be planned by healthcare professionals. Objectives: We evaluated the association between continuity (adherence or persistence) of treatment and several outcomes in patients with fragility fractures in the context of the development of the Italian Guidelines. Design: Systematic review. Data Sources and Methods: We systematically searched PubMed, Embase, and the Cochrane Library up to November 2020 for randomized clinical trials (RCTs) and observational studies that analyzed medication holidays in patients with fragility fracture. Three authors independently extracted data and appraised the risk of bias of the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random effects models. Primary outcomes were refracture and quality of life; secondary outcomes were mortality and treatment-related adverse events. Results: Six RCTs and nine observational studies met our inclusion criteria, ranging from very low to moderate quality. The adherence to antiosteoporotic drugs was associated with a lower risk of nonvertebral fracture [relative risk (RR) 0.42, 95% confidence interval (CI) 0.20–0.87; three studies] than nonadherence, whereas no difference was detected in the health-related quality of life. A reduction in refracture risk was observed when continuous treatment was compared to discontinuous therapy (RR 0.49, 95% CI 0.25–0.98; three studies). A lower mortality rate was detected for the adherence and persistence measures, while no significant differences were noted in gastrointestinal side effects in individuals undergoing continuous versus discontinuous treatment. Conclusion: Our findings suggest that clinicians should promote adherence and persistence to antiosteoporotic treatment in patients with fragility fractures unless serious adverse effects occur