Using ceftazidime-avibactam for persistent carbapenem-resistant Serratia marcescens infection highlights antimicrobial stewardship challenges with new beta-lactam-inhibitor combination antibiotics

The newer beta-lactam-inhibitor combination (BLIC) antibiotics are available in South Africa (SA) for the treatment of carbapenem-resistant Enterobacterales infections. We describe the successful use of ceftazidime-avibactam (CA) for the treatment of a child with persistent carbapenem-resistant Serratia marcescens bacteraemia, and the challenges faced using this lifesaving antibiotic, including access to susceptibility testing, procurement process, cost and complexity of deciding when, how and for how long to use it. Furthermore, the burden of carbapenem resistance is increasing in SA, and inappropriate use of CA and other newer BLIC antibiotics, such as ceftolozane-tazobactam, will inevitably endanger their longevity. A careful balance must be struck between removing unnecessary obstacles and delays in initiating these antibiotics for life-threatening infections, and additional antimicrobial stewardship-guided interventions aimed at preserving their therapeutic use

Developmental change in the association between adolescent depressive symptoms and the home environment: results from a longitudinal, genetically informative investigation

Background: Depression is already highly prevalent by late adolescence, indicating that research into its developmental emergence should consider earlier risk factors and environmental contexts. The home environment is a key context for children and adolescents throughout development. However, the nature of relationships that exist between aspects of the home environment and the development of depressive symptoms cannot be assumed. Genetically informative studies have been used to provide insights about the aetiology of such relationships, often finding them to be partly confounded by the influence of children's genes. Here, we investigate developmental change in the aetiology of the association between aspects of the home environment and depressive symptoms at the onset of adolescence. Methods: We used longitudinal child‐ and parent‐report data from >5,000 twin pairs enrolled in the UK‐representative Twins Early Development Study. Multivariate, genetically sensitive structural equation models were used to decompose latent variance and covariance in depressive symptoms (measured at 12 and 16 years) and aspects of the home environment (at 9 and 14 years) into genetic and environmental influences. Results: Going from childhood to adolescence, genetic influences accounted for an increasing proportion of the association [30% (16–42) of r = .44 in childhood; 40% (25–61) of r = .43 in adolescence], at the expense of shared environmental influences, which decreased from 70% (58–83) to 48% (29–62). Unique environmental influences accounted for a significant proportion of the association in adolescence only [12% (06–18)]. Developmental changes could largely be attributed to subtle shifts in the relative importance of stable aetiological factors, rather than the emergence of influences unique to adolescence. Conclusions: These findings emphasise the importance of developmental and aetiological context in interpreting associations between aspects of the home environment and child emotional outcomes

Etiological influences on perceptions of parenting: A longitudinal, multi-informant twin study

Children and their parents often differ in their perception of the relationship they share. As this relationship changes developmentally, the nature of these differences may also change. Longitudinal genetic designs can be used to investigate the developmental etiologies of shared and distinct perceptions. In this study, we used longitudinal psychometric models to analyze child and parent reports of negative parenting for 6417 twin pairs from the Twins Early Development Study at ages 9, 12 and 14 years. Within-time cross-reporter correlations, indicating the degree to which children and parents perceived negative parenting behaviors similarly at each age, were moderate (r = .44 − .46). Longitudinal genetic analyses revealed these shared perceptions to be relatively stable during the transition into adolescence, with this stability driven by a combination of children’s genetic factors and family-wide environmental factors. In contrast, child- and parent-specific perceptions of parenting were predominantly age-specific, a developmental pattern underpinned by child genetic factors and a combination of family-wide and unique environmental influences. These results and their implications are discussed in the context of interplay between reciprocal interactions, subjective insight and developmental behavioral change in the parent–child relationship

From Marx to Gramsci to us: Laboratory to prison, and back

Marx and Gramsci remain two of the most constant presences and inspirations for those on the left. Yet there is a persistent sense that we have still to get them right. Perhaps this indicates that sources like this are now fully classics, to be returned, and returned to. In the case of Marx and Gramsci, a series of major works published in the Brill Historical Materialism series breaks new ground as well as returning to older controversies, both resolved and unresolved. Apart from remaining arguments concerning the status of materials unpublished in their own lifetimes, the major tension that emerges here is that between the task of immanent, contextual philology and the challenge of reading ‘Marx for today’ or ‘Gramsci for today’. The tension between text and context, and the question of what travels, conceptually persists

Genetics of co-developing conduct and emotional problems during childhood and adolescence

Common genetic influences offer a partial explanation for comorbidity between different psychiatric disorders1,2,3. However, the genetics underlying co-development—the cross-domain co-occurrence of patterns of change over time—of psychiatric symptoms during childhood and adolescence has not been well explored. Here, we show genetic influence on joint symptom trajectories of parent-reported conduct and emotional problems (overall N = 15,082) across development (4–16 years) using both twin- and genome-wide polygenic score analyses (genotyped N = 2,610). Specifically, we found seven joint symptom trajectories, including two characterized by jointly stable and jointly increasing symptoms of conduct and emotional problems, respectively (7.3% of the sample, collectively). Twin modelling analyses revealed substantial genetic influence on trajectories (heritability estimates range of 0.41–0.78). Furthermore, individuals’ risk of being classified in the most symptomatic trajectory classes was significantly predicted by polygenic scores for years-of-education-associated alleles and depressive symptoms-associated alleles. Complementary analyses of child self-reported symptoms across late childhood and early adolescence yielded broadly similar results. Taken together, our results indicate that genetic factors are involved in the co-development of conduct and emotional problems across childhood and adolescence, and that individuals with co-developing symptoms across multiple domains may represent a clinical subgroup characterized by increased levels of genetic risk

Magnetization reversal processes in epitaxial Fe/GaAs(001) films

Copyright © 1994 American Institute of PhysicsIn this article we present the results of a detailed study of the switching behavior observed in epitaxial single Fe films of thickness between 30 and 450 Å, and a wedge shaped Fe film with a thickness range of 10–60 Å grown on GaAs (001). These films have cubic and uniaxial anisotropies which change with film thickness. For the fixed thickness films the values of the anisotropy constants were accurately determined by Brillouin light scattering (BLS) measurements together with polar magneto‐optic Kerr effect (MOKE) measurements that gave the value of the magnetization. The switching behavior of these samples was observed with in‐plane MOKE magnetometry as a function of the angle between the applied field and the in‐plane crystallographic axes. Measurements of the component of magnetization perpendicular to the applied field allow a precise determination of the relative orientation of the hard and easy in‐plane anisotropy axes. This can be used to accurately determine the ratio of uniaxial to cubic anisotropy constants, when this ratio is less than one. The ratios obtained from MOKE agree well with those obtained from BLS. Minimum energy calculations predict that the reversal process should proceed by a continuous rotation of the magnetization vector with either one or two irreversible jumps, depending on the applied field orientation and the nature of the anisotropy of the film. The calculations provide a good qualitative description of the observed reversal process, although the magnetic microstructure influences the exact values of the switching fields

Modeling saltwater intrusion scenarios for a coastal aquifer at the German North Sea

A 3d regional density-driven flow model of a heterogeneous aquifer system at the German North Sea Coast is set up within the joint project NAWAK (“Development of sustainable adaption strategies for the water supply and distribution infrastructure on condition of climatic and demographic change”). The development of the freshwater-saltwater interface is simulated for three climate and demographic scenarios. Groundwater flow simulations are performed with the finite volume code d3f++ (distributed density driven flow) that has been developed with a view to the modelling of large, complex, strongly density-influenced aquifer systems over long time periods

Short-term outcomes of down-referral in provision of paediatric antiretroviral therapy at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa: A retrospective cohort study

Background. The large scale-up of paediatric HIV care necessitated down-referral of many children receiving antiretroviral therapy (ART) from Red Cross War Memorial Children’s Hospital (RCWMCH), Cape Town, South Africa. Few published data exist on the outcomes of these children.Objectives. To assess outcomes of children receiving ART in the first 12 months after down-referral to primary healthcare (PHC) clinics and identify determinants of successful down-referral.Methods. A retrospective cohort study of children <15 years of age who initiated ART at RCWMCH and were subsequently down-referred to one of two PHC clinics between January 2006 and December 2012 was completed. Baseline characteristics of patients and caregivers as well as CD4+ counts, viral loads (VLs) and weights were collected 6 and 12 months after down-referral. Outcomes included retention in care and viral suppression.Results. Of 116 children down-referred to the two study PHC clinics, 81.9% arrived at the designated PHC clinic and a further 8.6% continued care at other clinics, the remaining 9.5% being lost to follow-up. Of those successfully down-referred, 11.4% took >8 weeks to present, possibly experiencing treatment interruption. At 12 months after down-referral, only 81.0% remained in care. No factors were associated with retention in care in multivariable analysis. For children who remained in care at the designated PHC clinics, the clinical and immunological gains achieved prior to down-referral were sustained through 12 months of follow-up, and 54.7% of this cohort had documented viral suppression at 12 months. However, if only children with VL results are considered, 75.9% (41/54) were virally suppressed 12 months after down-referral.Conclusions. Down-referral of children on ART is complex, with risk of loss to follow-up and treatment interruption.