Port Moresby

Non-fiction by Gilbert J. Otto

Clinical Characteristics and Outcomes of Patients With Cutibacterium acnes Endocarditis

Importance: It is suggested that patients with Cutibacterium acnes endocarditis often present without fever or abnormal inflammatory markers. However, no study has yet confirmed this statement. Objective: To assess the clinical characteristics and outcomes of patients with C acnes endocarditis. Design, Setting, and Participants: A case series of 105 patients presenting to 7 hospitals in the Netherlands and France (4 university hospitals and 3 teaching hospitals) with definite endocarditis according to the modified Duke criteria between January 1, 2010, and December 31, 2020, was performed. Clinical characteristics and outcomes were retrieved from medical records. Cases were identified by blood or valve and prosthesis cultures positive for C acnes, retrieved from the medical microbiology databases. Infected pacemaker or internal cardioverter defibrillator lead cases were excluded. Statistical analysis was performed in November 2022. Main Outcomes and Measures: Main outcomes included symptoms at presentation, presence of prosthetic valve endocarditis, laboratory test results at presentation, time to positive results of blood cultures, 30-day and 1-year mortality rates, type of treatment (conservative or surgical), and endocarditis relapse rates. Results: A total of 105 patients (mean [SD] age, 61.1 [13.9] years; 96 men [91.4%]; 93 patients [88.6%] with prosthetic valve endocarditis) were identified and included. Seventy patients (66.7%) did not experience fever prior to hospital admission, nor was it present at hospitalization. The median C-reactive protein level was 3.6 mg/dL (IQR, 1.2-7.5 mg/dL), and the median leukocyte count was 10.0 × 103/µL (IQR, 8.2-12.2 × 103/µL). The median time to positive blood culture results was 7 days (IQR, 6-9 days). Surgery or reoperation was indicated for 88 patients and performed for 80 patients. Not performing the indicated surgical procedure was associated with high mortality rates. Seventeen patients were treated conservatively, in accordance with the European Society of Cardiology guideline; these patients showed relatively high rates of endocarditis recurrence (5 of 17 [29.4%]). Conclusions and Relevance: This case series suggests that C acnes endocarditis was seen predominantly among male patients with prosthetic heart valves. Diagnosing C acnes endocarditis is difficult due to its atypical presentation, with frequent absence of fever and inflammatory markers. The prolonged time to positivity of blood culture results further delays the diagnostic process. Not performing a surgical procedure when indicated seems to be associated with higher mortality rates. For prosthetic valve endocarditis with small vegetations, there should be a low threshold for surgery because this group seems prone to endocarditis recurrence.</p

Chemical Elemental Distribution and Soil DNA Fingerprints Provide the Critical Evidence in Murder Case Investigation

Background: The scientific contribution to the solution of crime cases, or throughout the consequent forensic trials, is a crucial aspect of the justice system. The possibility to extract meaningful information from trace amounts of samples, and to match and validate evidences with robust and unambiguous statistical tests, are the key points of such process. The present report is the authorized disclosure of an investigation, carried out by Attorney General appointment, on a murder case in northern Italy, which yielded the critical supporting evidence for the judicial trial. Methodology/Principal Findings: The proportional distribution of 54 chemical elements and the bacterial community DNA fingerprints were used as signature markers to prove the similarity of two soil samples. The first soil was collected on the crime scene, along a corn field, while the second was found in trace amounts on the carpet of a car impounded from the main suspect in a distant location. The matching similarity of the two soils was proven by crossing the results of two independent techniques: a) elemental analysis via inductively coupled plasma mass spectrometry (ICP-MS) and optical emission spectrometry (ICP-OES) approaches, and b) amplified ribosomal DNA restriction analysis by gel electrophoresis (ARDRA). Conclusions: Besides introducing the novel application of these methods to forensic disciplines, the highly accurate level of resolution observed, opens new possibilities also in the fields of soil typing and tracking, historical analyses, geochemical surveys and global land mapping

Judging parental competence: A cross‐country analysis of judicial decision makers' written assessment of mothers' parenting capacities in newborn removal cases

This paper examines the discretionary reasoning of the judiciary in three jurisdictions, England, Germany and Norway, in cases deciding whether a newborn child is safe with her parents or intervention is necessary. Our analysis focuses on one specific dimension of decision makers' exercise of discretion, namely, if and how the strengths and weaknesses of the mother are considered. The data material consists of all decisions concerning care orders of newborns from one large city in Germany from 2015 to 2017 (n = 27) and 2016 in Norway (n = 76) and all publicly available newborn removal decisions in England for 2015–2017 (n = 14). The findings reveal a high number of risk factors in the cases and less focus on risk‐reducing factors. The situation of the newborn is considered to be harmful, as most cases result in a care order. Judicial discretion differs by how much information, and what types of factors, are included in the justification for the decision. A learning point for decision makers and policymakers would be to actively undertake a balancing act between risk‐increasing and risk‐reducing factors.publishedVersio

Loss of Sexual Reproduction and Dwarfing in a Small Metazoan

Asexuality has major theoretical advantages over sexual reproduction, yet newly formed asexual lineages rarely endure. The success, or failure, of such lineages is affected by their mechanism of origin, because it determines their initial genetic makeup and variability. Most previously described mechanisms imply that asexual lineages are randomly frozen subsamples of a sexual population.We found that transitions to obligate parthenogenesis (OP) in the rotifer Brachionus calyciflorus, a small freshwater invertebrate which normally reproduces by cyclical parthenogenesis, were controlled by a simple Mendelian inheritance. Pedigree analysis suggested that obligate parthenogens were homozygous for a recessive allele, which caused inability to respond to the chemical signals that normally induce sexual reproduction in this species. Alternative mechanisms, such as ploidy changes, could be ruled out on the basis of flow cytometric measurements and genetic marker analysis. Interestingly, obligate parthenogens were also dwarfs (approximately 50% smaller than cyclical parthenogens), indicating pleiotropy or linkage with genes that strongly affect body size. We found no adverse effects of OP on survival or fecundity.This mechanism of inheritance implies that genes causing OP may evolve within sexual populations and remain undetected in the heterozygous state long before they get frequent enough to actually cause a transition to asexual reproduction. In this process, genetic variation at other loci might become linked to OP genes, leading to non-random associations between asexuality and other phenotypic traits

John Evans Study Committee Recommendations

With the completion of this report the University of Denver is presented with an opportunity to reflect on our institutional origins, history, and legacy. We have an opportunity to provide a model of transparency, accountability, and transformation for institutions that have directly profited or indirectly benefited from the displacement of the indigenous communities whose lands and histories they occupy. This moment invites us to bend the arc of history away from the clamor of old apologetics that have caused deep wounds for those whose voices have been silenced and toward justice, healing, and peace. This likewise holds for those whose privilege and power has been upheld by historical noise, silence, and intentional omission. This is truly a new horizon and DU should be a change leader illuminating a new path forward: a path of unity, collaboration, and healing for all communities

Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis

Visceral leishmaniasis causes considerable mortality and morbidity in many parts of the world. There is an urgent need for the development of new, effective treatments for this disease. Here we describe the development of an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound from this series (7, DDD853651/GSK3186899) is efficacious in a mouse model of visceral leishmaniasis, has suitable physicochemical, pharmacokinetic and toxicological properties for further development, and has been declared a preclinical candidate. Detailed mode-of-action studies indicate that compounds from this series act principally by inhibiting the parasite cdc-2-related kinase 12 (CRK12), thus defining a druggable target for visceral leishmaniasis