Deborah Borda, now head of the New York Philharmonic, talks leadership in the coronavirus crisis. Her strategy: Invest in a future that people want.

The general manager of the Troubadour, which famously launched Elton John's career, says 'to survive, we're going to need all the help we can get.'

“I can’t go back,” says Philippe Lançon, who wrote a memoir about his recovery from the massacre.

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

Optic atrophy 1 (OPA1) is a dynamin protein that mediates mitochondrial fusion at the inner membrane. OPA1 is also necessary for maintaining the cristae and thus essential for supporting cellular energetics. OPA1 exists as membrane-anchored long form (L-OPA1) and short form (S-OPA1) that lacks the transmembrane region and is generated by cleavage of L-OPA1. Mitochondrial dysfunction and cellular stresses activate the inner membrane–associated zinc metallopeptidase OMA1 that cleaves L-OPA1, causing S-OPA1 accumulation. The prevailing notion has been that L-OPA1 is the functional form, whereas S-OPA1 is an inactive cleavage product in mammals, and that stress-induced OPA1 cleavage causes mitochondrial fragmentation and sensitizes cells to death. However, S-OPA1 contains all functional domains of dynamin proteins, suggesting that it has a physiological role. Indeed, we recently demonstrated that S-OPA1 can maintain cristae and energetics through its GTPase activity, despite lacking fusion activity. Here, applying oxidant insult that induces OPA1 cleavage, we show that cells unable to generate S-OPA1 are more sensitive to this stress under obligatory respiratory conditions, leading to necrotic death. These findings indicate that L-OPA1 and S-OPA1 differ in maintaining mitochondrial function. Mechanistically, we found that cells that exclusively express L-OPA1 generate more superoxide and are more sensitive to Ca2+-induced mitochondrial permeability transition, suggesting that S-OPA1, and not L-OPA1, protects against cellular stress. Importantly, silencing of OMA1 expression increased oxidant-induced cell death, indicating that stress-induced OPA1 cleavage supports cell survival. Our findings suggest that S-OPA1 generation by OPA1 cleavage is a survival mechanism in stressed cells.

Triple negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer leading to the worst prognosis. Because current therapeutic approaches lack efficacy, there is a clinically unmet need for effective treatment alternatives. Herein, we demonstrate a promising strategy utilizing a tumor-targeting alkylphosphocholine (NM600) radiolabeled with ¹⁷⁷Lu for targeted radionuclide therapy (TRT) of TNBC. In two murine syngeneic models of TNBC, we confirmed excellent tumor targeting and rapid normal tissue clearance of the PET imaging analog ⁸⁶Y-NM600. Based on longitudinal PET/CT data acquired with ⁸⁶Y-NM600, we estimated the dosimetry of therapeutic ¹⁷⁷Lu-NM600, which showed larger absorbed doses in the tumor compared to normal tissues. Administration of ¹⁷⁷Lu-NM600 resulted in significant tumor growth inhibition and prolonged overall survival in mice bearing syngeneic 4T07 and 4T1 tumors. Complete response was attained in 60% of 4T07 bearing mice, but animals carrying aggressive 4T1 tumor grafts succumbed to metastatic progression. The injected activities used for treatment (9.25 and 18.5 MBq) were well tolerated, and only mild transient cytopenia was noted. Overall, our results suggest that ¹⁷⁷Lu-NM600 TRT has potential for treatment of TNBC and merits further exploration in a clinical setting.

Introduction: To use positron emission tomography coupled with computed tomography (¹⁸FDG-PET/CT) to identify a high-risk subgroup requiring therapeutic intensification among patients with locally advanced cervical cancer (LACC) and para-aortic lymph node (PALN) involvement. Methods: In this retrospective multicentric study, patients with LACC and PALN involvement concurrently treated with chemoradiotherapy and extended-field radiotherapy (EFR) between 2006 and 2016 were included. A senior nuclear medicine specialist in PET for gynaecologic oncology reviewed all ¹⁸FDG-PET/CT scans. Metabolic parameters including maximum standardised uptake value (SUV_max), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were determined for the primary tumour, pelvic lymph nodes and PALN. Associations between these parameters and overall survival (OS) were assessed with Cox's proportional hazards model. Results: Sixty-eight patients were enrolled in the study. Three-year OS was 55.5% (95% CI (40.8-68.0)). When adjusted for age, stage and histology, pelvic lymph node TLG, PALN TLG and PALN SUV_max were significantly associated with OS (p<0.005). Conclusion: FDG-PET/CT was able to identify predictors of survival in the homogeneous subgroup of patients with LACC and PALN involvement, thus allowing therapeutic intensification to be proposed.

Overexpression of somatostatin receptors in patients with neuroendocrine neoplasms (NEN) is utilized for both diagnosis and treatment. Receptor density may reflect tumor differentiation and thus be associated with prognosis. Non-invasive visualization and quantification of somatostatin receptor density is possible by somatostatin receptor imaging (SRI) using positron emission tomography (PET). Recently, we introduced ⁶⁴Cu-DOTATATE for SRI and we hypothesized that uptake of this tracer could be associated with overall (OS) and progression-free survival (PFS). Methods: We evaluated patients with NEN that had a ⁶⁴Cu-DOTATATE PET/CT SRI performed in two prospective studies. Tracer uptake was determined as the maximal standardized uptake value (SUV_max) for each patient. Kaplan-Meier analysis with log-rank was used to determine the predictive value of ⁶⁴Cu-DOTATATE SUV_max for OS and PFS. Specificity, sensitivity and accuracy was calculated for prediction of outcome at 24 months after ⁶⁴Cu-DOTATATE PET/CT. Results: A total of 128 patients with NEN were included and followed for a median of 73 (1-112) months. During follow-up, 112 experienced disease progression and 69 patients died. The optimal cutoff for ⁶⁴Cu-DOTATATE SUV_max was 43.3 for prediction of PFS with a hazard ratio of 0.56 (95% CI: 0.38-0.84) for patients with SUV_max > 43.3. However, no significant cutoff was found for prediction of OS. In multiple Cox regression adjusted for age, sex, primary tumor site and tumor grade, the SUV_max cutoff hazard ratio was 0.50 (0.32-0.77) for PFS. The accuracy was moderate for predicting PFS (57%) at 24 months after ⁶⁴Cu-DOTATATE PET/CT. Conclusion: In this first study to report the association of ⁶⁴Cu-DOTATATE PET/CT and outcome in patients with NEN, tumor somatostatin receptor density visualized with ⁶⁴Cu-DOTATATE PET/CT was prognostic for PFS but not OS. However, the accuracy of prediction of PFS at 24 months after ⁶⁴Cu-DOTATATE PET/CT SRI was moderate limiting the value on an individual patient basis.

Prostate specific membrane antigen (PSMA) targeting Positron Emission Tomography (PET) imaging is becoming the reference standard for prostate cancer (PC) staging, especially in advanced disease. Yet, the implications of PSMA-PET derived whole-body tumor volume for overall survival are poorly elucidated to date. This might be due to the fact that (semi-) automated quantification of whole-body tumor volume as PSMA-PET biomarker is an unmet clinical challenge. Therefore, a novel semi-automated software is proposed and evaluated by the present study, which enables the semi-automated quantification of PSMA-PET biomarkers such as whole-body tumor volume. Methods: The proposed quantification is implemented as a research prototype (MI Whole Body Analysis Suite, v1.0, Siemens Medical Solutions USA, Inc., Knoxville, TN). PSMA accumulating foci were automatically segmented by a percental threshold (50% of local SUV_max). Neural networks were trained to segment organs in PET-CT acquisitions (training CTs: 8,632, validation CTs: 53). Thereby, PSMA foci within organs of physiologic PSMA uptake were semi-automatically excluded from the analysis. Pretherapeutic PSMA-PET-CTs of 40 consecutive patients treated with ¹⁷⁷Lu-PSMA-617 therapy were evaluated in this analysis. The volumetric whole-body tumor volume (PSMATV50), SUV_max, SUVmean and other whole-body imaging biomarkers were calculated for each patient. Semi-automatically derived results were compared with manual readings in a sub-cohort (by one nuclear medicine physician using syngo.MM Oncology software, Siemens Healthineers, Knoxville, TN). Additionally, an inter-observer evaluation of the semi-automated approach was performed in a sub-cohort (by two nuclear medicine physicians). Results: Manually and semi automatically derived PSMA metrics were highly correlated (PSMATV50: R2=1.000; p<0.001; SUV_max: R2=0.988; p<0.001). The inter-observer agreement of the semi-automated workflow was also high (PSMATV50: R2=1.000; p<0.001; ICC=1.000; SUV_max: R2=0.988; p<0.001; ICC=0.997). PSMATV50 [ml] was a significant predictor of overall survival (HR: 1.004; 95%CI: 1.001-1.006, P = 0.002) and remained so in a multivariate regression including other biomarkers (HR: 1.004; 95%CI: 1.001-1.006 P = 0.004). Conclusion: PSMATV50 is a promising PSMA-PET biomarker that is reproducible and easily quantified by the proposed semi-automated software. Moreover, PSMATV50 is a significant predictor of overall survival in patients with advanced prostate cancer that receive ¹⁷⁷Lu-PSMA-617 therapy.

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

Swi-independent 3a and 3b (Sin3a and Sin3b) are paralogous transcriptional coregulators that direct cellular differentiation, survival, and function. Here, we report that mouse Sin3a and Sin3b are co-produced in most pancreatic cells during embryogenesis but become much more enriched in endocrine cells in adults, implying continued essential roles in mature endocrine-cell function. Mice with loss of Sin3a in endocrine progenitors were normal during early postnatal stages but gradually developed diabetes before weaning. These physiological defects were preceded by the compromised survival, insulin-vesicle packaging, insulin secretion, and nutrient-induced Ca²⁺ influx of Sin3a-deficient β-cells. RNA-seq coupled with candidate chromatin-immunoprecipitation assays revealed several genes that could be directly regulated by Sin3a in β-cells, which modulate Ca²⁺/ion transport, cell survival, vesicle/membrane trafficking, glucose metabolism, and stress responses. Lastly, mice with loss of both Sin3a and Sin3b in multipotent embryonic pancreatic progenitors had significantly reduced islet-cell mass at birth, caused by decreased endocrine-progenitor production and increased β-cell death. These findings highlight the stage-specific requirements for the presumed "general" coregulators Sin3a and Sin3b in islet β-cells, with Sin3a being dispensable for differentiation but required for postnatal function and survival.

Islet transplantation is an emerging therapy for type 1 diabetes (T1D) and hypoglycaemic unawareness. However, a key challenge for islet transplantation is cellular rejection and the requirement for long-term immunosuppression. In this study we established a diabetic-humanized NOD-scidIL2R^null(NSG) mouse model of T cell mediated human islet-allograft rejection and developed a therapeutic regimen of low-dose recombinant human interleukin2(IL-2) combined with low-dose rapamycin to prolong graft survival. NSG-mice that had received renal-subcapsular human islet-allografts and were transfused with 1x10⁷ of human-spleen-mononuclear-cells (hSPMCs), reconstituted human CD45⁺ cells that were predominantly CD3⁺ T cells and rejected their grafts with a median survival time of 27 days. IL-2 alone (0.3x10⁶ IU/m² or 1x10⁶ IU/m²), or rapamycin alone (0.5-1mg/kg) for 3 weeks did not prolong survival. However, the combination of rapamycin with IL-2 for 3 weeks significantly prolonged human islet-allograft survival. Graft survival was associated with expansion of CD4⁺CD25⁺FOXP3⁺ Tregs and enhanced TGF-β production by CD4⁺ T cells. CD8⁺ T cells showed reduced IFN- production and reduced expression of perforin-1. The combination of IL-2 and rapamycin has the potential to inhibit human islet-allograft rejection by expanding CD4⁺FOXP3⁺ Tregs in vivo and supressing effector cell function, and could be the basis of effective tolerance-based regimens.

Optic atrophy 1 (OPA1) is a dynamin protein that mediates mitochondrial fusion at the inner membrane. OPA1 is also necessary for maintaining the cristae and thus essential for supporting cellular energetics. OPA1 exists as membrane-anchored long form (L-OPA1) and short form (S-OPA1) that lacks the transmembrane region and is generated by cleavage of L-OPA1. Mitochondrial dysfunction and cellular stresses activate the inner membrane–associated zinc metallopeptidase OMA1 that cleaves L-OPA1, causing S-OPA1 accumulation. The prevailing notion has been that L-OPA1 is the functional form, whereas S-OPA1 is an inactive cleavage product in mammals, and that stress-induced OPA1 cleavage causes mitochondrial fragmentation and sensitizes cells to death. However, S-OPA1 contains all functional domains of dynamin proteins, suggesting that it has a physiological role. Indeed, we recently demonstrated that S-OPA1 can maintain cristae and energetics through its GTPase activity, despite lacking fusion activity. Here, applying oxidant insult that induces OPA1 cleavage, we show that cells unable to generate S-OPA1 are more sensitive to this stress under obligatory respiratory conditions, leading to necrotic death. These findings indicate that L-OPA1 and S-OPA1 differ in maintaining mitochondrial function. Mechanistically, we found that cells that exclusively express L-OPA1 generate more superoxide and are more sensitive to Ca2+-induced mitochondrial permeability transition, suggesting that S-OPA1, and not L-OPA1, protects against cellular stress. Importantly, silencing of OMA1 expression increased oxidant-induced cell death, indicating that stress-induced OPA1 cleavage supports cell survival. Our findings suggest that S-OPA1 generation by OPA1 cleavage is a survival mechanism in stressed cells.

OBJECTIVE

In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients.

Diabetes in pregnancy -- Treatment -- Popular works.

1953.

1953.

Francisco Cribari-Neto, Rodney V. Fonseca.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 2, 329--355.

Abstract:
The log-linear Birnbaum–Saunders model has been widely used in empirical applications. We introduce an extension of this model based on a recently proposed version of the Birnbaum–Saunders distribution which is more flexible than the standard Birnbaum–Saunders law since its density may assume both unimodal and bimodal shapes. We show how to perform point estimation, interval estimation and hypothesis testing inferences on the parameters that index the regression model we propose. We also present a number of diagnostic tools, such as residual analysis, local influence, generalized leverage, generalized Cook’s distance and model misspecification tests. We investigate the usefulness of model selection criteria and the accuracy of prediction intervals for the proposed model. Results of Monte Carlo simulations are presented. Finally, we also present and discuss an empirical application.

Imad Bou-Hamad, Denis Larocque, Hatem Ben-Ameur

Source: Statist. Surv., Volume 5, 44--71.

Abstract:
This paper presents a non–technical account of the developments in tree–based methods for the analysis of survival data with censoring. This review describes the initial developments, which mainly extended the existing basic tree methodologies to censored data as well as to more recent work. We also cover more complex models, more specialized methods, and more specific problems such as multivariate data, the use of time–varying covariates, discrete–scale survival data, and ensemble methods applied to survival trees. A data example is used to illustrate some methods that are implemented in R.

This paper is devoted to the R package JSM which performs joint statistical modeling of survival and longitudinal data. In biomedical studies it has been increasingly common to collect both baseline and longitudinal covariates along with a possibly censored survival time. Instead of analyzing the survival and longitudinal outcomes separately, joint modeling approaches have attracted substantive attention in the recent literature and have been shown to correct biases from separate modeling approaches and enhance information. Most existing approaches adopt a linear mixed effects model for the longitudinal component and the Cox proportional hazards model for the survival component. We extend the Cox model to a more general class of transformation models for the survival process, where the baseline hazard function is completely unspecified leading to semiparametric survival models. We also offer a non-parametric multiplicative random effects model for the longitudinal process in JSM in addition to the linear mixed effects model. In this paper, we present the joint modeling framework that is implemented in JSM, as well as the standard error estimation methods, and illustrate the package with two real data examples: a liver cirrhosis data and a Mayo Clinic primary biliary cirrhosis data.

Wenjie Wang, Robert Aseltine, Kun Chen, Jun Yan.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 51--73.

Abstract:
The concept of integrating data from disparate sources to accelerate scientific discovery has generated tremendous excitement in many fields. The potential benefits from data integration, however, may be compromised by the uncertainty due to incomplete/imperfect record linkage. Motivated by a suicide risk study, we propose an approach for analyzing survival data with uncertain event times arising from data integration. Specifically, in our problem deaths identified from the hospital discharge records together with reported suicidal deaths determined by the Office of Medical Examiner may still not include all the death events of patients, and the missing deaths can be recovered from a complete database of death records. Since the hospital discharge data can only be linked to the death record data by matching basic patient characteristics, a patient with a censored death time from the first dataset could be linked to multiple potential event records in the second dataset. We develop an integrative Cox proportional hazards regression in which the uncertainty in the matched event times is modeled probabilistically. The estimation procedure combines the ideas of profile likelihood and the expectation conditional maximization algorithm (ECM). Simulation studies demonstrate that under realistic settings of imperfect data linkage the proposed method outperforms several competing approaches including multiple imputation. A marginal screening analysis using the proposed integrative Cox model is performed to identify risk factors associated with death following suicide-related hospitalization in Connecticut. The identified diagnostics codes are consistent with existing literature and provide several new insights on suicide risk, prediction and prevention.

Byron C. Jaeger, D. Leann Long, Dustin M. Long, Mario Sims, Jeff M. Szychowski, Yuan-I Min, Leslie A. Mcclure, George Howard, Noah Simon.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1847--1883.

Abstract:
We introduce and evaluate the oblique random survival forest (ORSF). The ORSF is an ensemble method for right-censored survival data that uses linear combinations of input variables to recursively partition a set of training data. Regularized Cox proportional hazard models are used to identify linear combinations of input variables in each recursive partitioning step. Benchmark results using simulated and real data indicate that the ORSF’s predicted risk function has high prognostic value in comparison to random survival forests, conditional inference forests, regression and boosting. In an application to data from the Jackson Heart Study, we demonstrate variable and partial dependence using the ORSF and highlight characteristics of its ten-year predicted risk function for atherosclerotic cardiovascular disease events (ASCVD; stroke, coronary heart disease). We present visualizations comparing variable and partial effect estimation according to the ORSF, the conditional inference forest, and the Pooled Cohort Risk equations. The obliqueRSF R package, which provides functions to fit the ORSF and create variable and partial dependence plots, is available on the comprehensive R archive network (CRAN).

Hydrocephalus is a pathologic condition associated with various brain diseases, including Alzheimer's disease (AD). Dysfunctional ependymal cells (EpCs) are believed to contribute to the development of hydrocephalus. It is thus of interest to investigate EpCs' development and function. Here, we report that vacuolar protein sorting-associated protein 35 (VPS35) is critical for EpC differentiation, ciliogenesis, and survival, and thus preventing neonatal hydrocephalus. VPS35 is abundantly expressed in EpCs. Mice with conditional knock-out (cKO) of Vps35 in embryonic (Vps35^GFAP-Cre and Vps35^Emx1-Cre) or postnatal (Vps35^Foxj1-CreER) EpC progenitors exhibit enlarged lateral ventricles (LVs) and hydrocephalus-like pathology. Further studies reveal marked reductions in EpCs and their cilia in both Vps35^GFAP-Cre and Vps35^Foxj1-CreER mutant mice. The reduced EpCs appear to be due to impairments in EpC differentiation and survival. Additionally, both Vps35^GFAP-Cre and Vps35^Foxj1-CreER neonatal pups exhibit increased cell proliferation and death largely in a region close to LV-EpCs. Many microglia close to the mutant LV-EpC region become activated. Depletion of the microglia by PLX3397, an antagonist of colony-stimulating factor 1 receptor (CSF1R), restores LV-EpCs and diminishes the pathology of neonatal hydrocephalus in Vps35^Foxj1-CreER mice. Taken together, these observations suggest unrecognized functions of Vps35 in EpC differentiation, ciliogenesis, and survival in neonatal LV, and reveal pathologic roles of locally activated microglia in EpC homeostasis and hydrocephalus development.

SIGNIFICANCE STATEMENT This study reports critical functions of vacuolar protein sorting-associated protein 35 (VPS35) not only in promoting ependymal cell (EpC) differentiation, ciliogenesis, and survival, but also in preventing local microglial activation. The dysfunctional EpCs and activated microglia are likely to induce hydrocephalus.

In a new twist on oral history, University of Alberta paleontologists have discovered that an Argentinian reptile from 95 million years ago developed a type of tooth enamel that is common in humans and other mammals but rare among reptiles.

The use of steroids as a treatment for patients with Duchenne muscular dystrophy results in a slower progression in weakness. Bisphosphonates often are used in conjunction with steroid therapy to enhance bone health.

The combination of steroids and bisphosphonates seems to be associated with significantly improved survival rates compared with treatment with steroids alone. (Read the full article)

Survival of children born with Down syndrome has been improving, but few studies have used population-based data to examine the influence of fetal and maternal characteristics on survival.

This study examined predictors of survival for children born with Down syndrome using population-based data from the UK Northern Congenital Abnormality Survey and shows that year of birth, gestational age, birth weight, and presence of additional anomalies influence survival status. (Read the full article)

Although survival of children born with Down syndrome has improved, unexplained racial and ethnic disparities in survival persist in the United States.

This study used population-based data from 10 birth defects monitoring programs in the United States to examine survival trends among children born with Down syndrome and to evaluate the changing influence of survival predictors over the life course. (Read the full article)

Survival estimates for preterm infants are vital for counseling parents, informing care, and planning services. Widely use estimates of in-unit survival derived from a large UK population for infants born at <33 weeks’ gestational age have been available since 1999.

These survival charts have been updated and will be of use to clinicians, parents, and managers. An alternative method for graphical representation of survival probabilities is offered: contour survival plots. (Read the full article)

Pulse oximetry testing in newborns can detect asymptomatic cases of critical congenital heart defects and has been added to the US Recommended Uniform Screening Panel. However, the impact that earlier diagnosis may have on survival in this population is unclear.

One-year survival for infants with critical congenital heart defects has been improving over time, yet mortality remains high. Survival has been greatest for those diagnosed after 1 day of age and may increase more with screening using pulse oximetry. (Read the full article)

Survival of children with spinal muscular atrophy type 1 is determined by treatment choice: tracheostomy with mechanical ventilation, noninvasive mechanical ventilation, or a palliative approach. Few data are available on life expectancies with different approaches.

The present study provides data comparing therapeutic strategies that affect life expectancy. Clinicians involved in the care of patients with spinal muscular atrophy type 1 should be aware of survival trends while awaiting more definitive therapeutic strategies. (Read the full article)

Germ cell tumors in children are heterogeneous and rare neoplasms that occur in various locations, such as gonads, the central nervous system, and the pelvis. The incidence rate has been increasing in some countries.

Population-based analyses of germ cell tumors in children are rare. This population-based study describes the incidence rates, trends, and survival of germ cell tumors in German children from 1987 to 2011. (Read the full article)

Embryonal tumors occur almost exclusively in children. The group is heterogeneous and includes relatively common pediatric tumors as well as rare tumors. The incidence rate for hepatoblastoma has been increasing in some countries.

This population-based study is the first comprehensive study on embryonal tumors in German children. Incidence rates, trends, and survival for 1991 through 2012 are presented. A statistically significant increasing trend for hepatoblastoma was detected for the first time in Europe. (Read the full article)

Hypoplastic left heart syndrome (HLHS) is a critical congenital heart defect with high mortality. With advances in surgical intervention in recent years, survival of infants with HLHS has improved, but information on long-term survival using population-based data is limited.

In this population-based study, survival to adolescence of children with HLHS has significantly improved in recent years. Among infant survivors, >90% survived up to 18 years. Gestational age, birth weight, and neighborhood poverty may affect survival. (Read the full article)

Allon Raiz is CEO of business incubator Raizcorp. In this series of articles, he offers entrepreneurs advice on surviving a crisis.

Now, more than ever, we need to be listening for market signals and ensuring that our businesses are primed to both take advantage of opportunities and to mitigate risks, says Allon Raiz.

Ease of Doing Business for MSMEs: All the government services like clearances, issuing licenses, approvals etc. should be online and time-bound. The onus of delay should be on the officer concerned and be made liable for payment of damages for causing delays.

The crisis has jeopardised India's 5 lakh crore tourism industry and employment of an estimated 3.8 crore jobs, FAITH said in a statement.

All states have been requested to give a complete waiver on all fixed electricity and other utility charges as well as excise duties without any penalties to the tourism and hospitality industry, FAITH said in a statement.

ISRO is already working on a Humanoid prototype (with a female form)for the Gaganyaan missions, which is expected to be sent out on a mission next year to test it out before actually sending humans in space.

Some creative hashtags on social media have come to the rescue of netizens, offering distraction as well as solace in these trying times.

A flailing leader has given Brazil’s generals an opening to insert themselves onto the front lines of politics.

It’s not just about the sperm: the semen of male fish carries unidentified substances that influence how quickly the offspring develop and even how well they can swim

Over half the world’s wild tigers now live 5 kilometres from a road, and infrastructure projects planned in Asia could fragment their habitat further

Title: One Sigmoidoscopy Boosts Colon Cancer Survival Odds
Category: Health News
Created: 4/27/2010 8:10:00 PM
Last Editorial Review: 4/28/2010 12:00:00 AM