Implementing Public Health Regulations in Developing Countries: Lessons from the OECD Countries

The enforcement of public health standards is a common problem in many developing countries. Public health agencies lack sufficient resources and, too often, enforcement mechanisms rely on slow and erratic judicial systems. These limitations can make traditional public health regulations difficult to implement. In this article, we examine innovative approaches to the implementation of public health regulations that have emerged in recent years within OECD countries. These approaches aim to improve compliance with health standards, while reducing dependence on both the legal system and the administrative resources of public health agencies. This article begins by discussing some traditional forms of public health regulations; these regulations include administrative searches and inspections as well as licensing measures. Within these traditional forms of public health regulation, there are several ways of improving compliance without substantially increasing administrative costs. These measures include public disclosure and several types of sanctions, which may escalate in severity as an actor continues to flout the public health regulation. In addition to such traditional measures, we discuss more creative approaches to reducing dependence on the judiciary and reducing administrative costs. Dependence on the judiciary can be reduced through increased reliance on alternative dispute resolution methods, such as mediation and arbitrations, as well as through the use of a public health Ombudsman. Administrative costs could also potentially be reduced through the creative use of public-private cooperation measures, such as negotiated rulemaking and self-regulating codes of conduct. Developing countries may find some useful lessons in the innovative approaches described; however, these approaches will likely need to be adapted to fit each country’s particular institutional setting

Meta-analysis of the gut microbiota in predicting response to cancer immunotherapy in metastatic melanoma

BACKGROUND. Identifying factors conferring responses to therapy in cancer is critical to select the best treatment for patients. For immune checkpoint inhibition (ICI) therapy, mounting evidence suggests that the gut microbiome can determine patient treatment outcomes. However, the extent to which gut microbial features are applicable across different patient cohorts has not been extensively explored. METHODS. We performed a meta-analysis of 4 published shotgun metagenomic studies (Ntot = 130 patients) investigating differential microbiome composition and imputed metabolic function between responders and nonresponders to ICI. RESULTS. Our analysis identified both known microbial features enriched in responders, such as Faecalibacterium as the prevailing taxa, as well as additional features, including overrepresentation of Barnesiella intestinihominis and the components of vitamin B metabolism. A classifier designed to predict responders based on these features identified responders in an independent cohort of 27 patients with the area under the receiver operating characteristic curve of 0.625 (95% CI: 0.348–0.899) and was predictive of prognosis (HR = 0.35, P = 0.081). CONCLUSION. These results suggest the existence of a fecal microbiome signature inherent across responders that may be exploited for diagnostic or therapeutic purposes

The End of the Canonical IoT Botnet: A Measurement Study of Mirai's Descendants

Since the burgeoning days of IoT, Mirai has been established as the canonical IoT botnet. Not long after the public release of its code, researchers found many Mirai variants compete with one another for many of the same vulnerable hosts. Over time, the myriad Mirai variants evolved to incorporate unique vulnerabilities, defenses, and regional concentrations. In this paper, we ask: have Mirai variants evolved to the point that they are fundamentally distinct? We answer this question by measuring two of the most popular Mirai descendants: Hajime and Mozi. To actively scan both botnets simultaneously, we developed a robust measurement infrastructure, BMS, and ran it for more than eight months. The resulting datasets show that these two popular botnets have diverged in their evolutions from their common ancestor in multiple ways: they have virtually no overlapping IP addresses, they exhibit different behavior to network events such as diurnal rate limiting in China, and more. Collectively, our results show that there is no longer one canonical IoT botnet. We discuss the implications of this finding for researchers and practitioners

The protective effect of the spleen in sickle cell patients. A comparative study between patients with asplenia/hyposplenism and hypersplenism

Sickle cell disease (SCD) is caused by a point mutation in the beta-globin gene. SCD is characterized by chronic hemolytic anemia, vaso-occlusive events leading to tissue ischemia, and progressive organ failure. Chronic inflammatory state is part of the pathophysiology of SCD. Patients with SCD have extremely variable phenotypes, from mild disease to severe complications including early age death. The spleen is commonly injured in SCD. Early splenic dysfunction and progressive spleen atrophy are common. Splenomegaly and hypersplenism can also occur with the loss of the crucial splenic function. Acute, life-threatening spleen-related complications in SCD are well studied. The association of laboratory parameters with the spleen status including hyposplenism, asplenia, and splenomegaly/hypersplenism, and their implication in vaso-occlusive crisis and long-term complications in SCD remain to be determined. We evaluated the association between the spleen status with clinical and laboratory parameters in 31 SCD patients: Group a) Patients with asplenia/hyposplenism (N = 22) (including auto-splenectomy and splenectomized patients) vs. Group b) patients with splenomegaly and or hypersplenism (N = 9). Laboratory studies included: Complete Blood Count, reticulocyte count, iron metabolism parameters, C Reactive Protein (CRP), Hb variant distribution, and D-dimer. Metabolic and morphological red blood cell (RBC) studies included: density gradient (by Percoll), glucose consumption, lactate release, and K$^{+}$ leakage, fetal RBC (F-Cells) and F-Reticulocytes, annexinV+, CD71$^{+}$, oxidative stress measured by GSH presence in RBC and finally Howell Jolly Bodies count were all analyzed by Flow Cytometry. Scanning electron microscopy analysis of RBC was also performed. Patients with asplenia/hyposplenism showed significantly higher WBC, platelet, Hematocrit, hemoglobin S, CRP, D-dimer, Gamma Glutamyl Transferase (GGT), cholesterol, transferrin, annexin V+ RBCs, CD71$^{+}$ RBCs, together with a markedly lower F Reticulocyte levels in comparison with splenomegaly/hypersplenism patients. In summary, important differences were also found between the groups in the studied RBCs parameters. Further studies are required to elucidate the effect of the spleen including hyper and hypo-splenia on laboratory parameters and in clinical manifestations, vascular pathology, and long-term complications of SCD. The benefits and risks of splenectomy compared to chronic transfusion need to be evaluated in clinical trials and the standard approach managing hypersplenism in SCD patients should be re-evaluated

Back to the "Gold Standard": How Precise is Hematocrit Detection Today?

Introduction: The commonly used method for hematocrit detection, by visual examination of microcapillary tube, known as "micro-HCT", is subjective but remains one of the key sources for fast hematocrit evaluation. Analytical automation techniques have increased the standardization of RBC index detection; however, indirect hematocrit measurements by blood analyzer, the automated HCT, do not correlate well with "micro-HCT" results in patients with hematological pathologies. We aimed to overcome those disadvantages in "micro-HCT" analysis using "ImageJ" processing software. Methods: 223 blood samples from the "general population" and 19 from sickle cell disease patients were examined in parallel for hematocrit values using the automated HCT, standard "micro-HCT," and "ImageJ" micro-HCT methods. Results: For the "general population" samples, the "ImageJ" values were significantly higher than the corresponding values evaluated by standard "micro-HCT" and automated HCT, except for the 0 to 2 month old newborns, in which the automated HCT results were similar to the "ImageJ" evaluated HCT. Similar to the "general population" cohort, we found significantly higher values measured by "ImageJ" compared to either "micro-HCT" or the automated HCT in SCD patients. Correspondent differences for the MCV and MCHC were also found. Discussion: This study introduces the "micro-HCT" assessment technique using the image-analysis module of "ImageJ" software. This procedure allows overcoming most of the data errors associated with the standard "micro-HCT" evaluation and can replace the use of complicated and expensive automated equipment. The presented results may also be used to develop new standards for calculating hematocrit and associated parameters for routine clinical practice. Keywords: Image analysis; Microcapillary hematocrit; RBC indices

Analysis of normal levels of free glycosaminoglycans in urine and plasma in adults

Plasma and urine glycosaminoglycans (GAGs) are long, linear sulfated polysaccharides that have been proposed as potential noninvasive biomarkers for several diseases. However, owing to the analytical complexity associated with the measurement of GAG concentration and disaccharide composition (the so-called GAGome), a reference study of the normal healthy GAGome is currently missing. Here, we prospectively enrolled 308 healthy adults and analyzed their free GAGomes in urine and plasma using a standardized ultra-high-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry method together with comprehensive demographic and blood chemistry biomarker data. Of 25 blood chemistry biomarkers, we mainly observed weak correlations between the free GAGome and creatinine in urine and hemoglobin or erythrocyte counts in plasma. We found a higher free GAGome concentration - but not a more diverse composition - in males. Partitioned by gender, we also established reference intervals for all detectable free GAGome features in urine and plasma. Finally, we carried out a transference analysis in healthy individuals from two distinct geographical sites, including data from the Lifelines Cohort Study, which validated the reference intervals in urine. Our study is the first large-scale determination of normal free GAGomes reference intervals in plasma and urine and represents a critical resource for future physiology and biomarker research