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Neonatal hematology is a fast-growing field, and the majority of sick neonates will develop hematological problems. This is an essential guide to the pathogenesis, diagnosis and management of hematologic problems in the neonate. Guidance is practical, including blood test interpretation, advice on transfusions and reference ranges for hematological values. Chapters have been thoroughly revised according to the latest advances in the field for this updated third edition. Topics discussed include erythrocyte disorders, platelet disorders, leukocyte disorders, immunologic disorders and hemostatic disorders. Coverage of oncological issues has been expanded to two separate chapters on leukemia and solid tumors, making information more easily accessible. Approaches to identifying the cause of anemia in a neonate are explained, with detailed algorithms provided to aid clinicians in practice. Covering an important hematologic niche with an ever increasing amount of specialized knowledge, this book is a valuable resource for hematologists, neonatologists and pediatricians.
Preeclampsia (PE) and gestational hypertension (GH) are pregnancy-specific diseases that occur in around 10% of pregnancies worldwide. Increasing evidence suggests that women whose pregnancies were complicated by PE or GH, and their offspring, are at increased risk of cardiovascular disease (CVD) later in life. We hypothesised that PE and GH would associate with CVD risk factors 8–10 years after the first pregnancy in the mother and child and that differences in cardiovascular risk profile would be seen between 8- and 10-year-old male and female children. This is a follow-up study of the Adelaide SCOPE pregnancy cohort where 1164 nulliparous women and their babies were recruited between 2005 and 2008. Haemodynamic function was assessed using non-invasive USCOMBP+ and USCOM1A devices. Microvascular function was assessed by post-occlusive reactive hyperaemia. Of the 273 mother–child pairs followed up, 38 women had PE and 20 had GH during pregnancy. Augmentation index (Aix) and suprasystolic pulse pressure (ssPP) were increased, whereas measures of microvascular function were decreased in children who were born to PE compared to uncomplicated pregnancies. Female children had decreased Aix and ssPP compared to male children after in utero exposure to PE. Women who developed GH during their first pregnancy had increased systolic, diastolic and mean arterial pressures compared to women who had uncomplicated pregnancy. Our data suggest that GH is associated with increased cardiovascular risk in women 8–10 years after first pregnancy and PE is associated with increased offspring risk at 8–10 years of age, highlighting differences between these two hypertensive disorders of pregnancy.
This study describes a procedural blank assessment of the ultraviolet photochemical oxidation (UV oxidation) method that is used to measure carbon isotopes of dissolved organic carbon (DOC) at the National Ocean Sciences Accelerator Mass Spectrometry Facility (NOSAMS). A retrospective compilation of Fm and δ13C results for secondary standards (OX-II, glycine) between 2009 and 2018 indicated that a revised blank correction was required to bring results in line with accepted values. The application of a best-fit mass-balance correction yielded a procedural blank of 22.0 ± 6.0 µg C with Fm of 0.30 ± 0.20 and δ13C of –32.0 ± 3.0‰ for this period, which was notably higher and more variable than previously reported. Changes to the procedure, specifically elimination of higher organic carbon reagents and improved sample and reactor handling, reduced the blank to 11.0 ± 2.75 µg C, with Fm of 0.14 ± 0.10 and δ13C of –31.0 ± 5.5‰. A thorough determination of the entire sample processing blank is required to ensure accurate isotopic compositions of seawater DOC using the UV oxidation method. Additional efforts are needed to further reduce the procedural blank so that smaller DOC samples can be analyzed, and to increase sample throughput.
Recent experimental and computational studies indicate that near-wall turbulent flows can be characterized by universal small-scale autonomous dynamics that is modulated by large-scale structures. We formulate numerical simulations of near-wall turbulence in a small domain localized to the boundary, whose size scales in viscous units. To mimic the environment in which the near-wall turbulence evolves, the formulation accounts for the flux of mean momentum through the upper boundary of the domain. Comparisons of the model's two-dimensional energy spectra and low-order single-point statistics with the corresponding quantities computed from direct numerical simulations indicate that it successfully captures the dynamics of the small-scale near-wall turbulence.
Many studies document cognitive decline following specific types of acute illness hospitalizations (AIH) such as surgery, critical care, or those complicated by delirium. However, cognitive decline may be a complication following all types of AIH. This systematic review will summarize longitudinal observational studies documenting cognitive changes following AIH in the majority admitted population and conduct meta-analysis (MA) to assess the quantitative effect of AIH on post-hospitalization cognitive decline (PHCD).
We followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria were defined to identify studies of older age adults exposed to AIH with cognitive measures. 6566 titles were screened. 46 reports were reviewed qualitatively, of which seven contributed data to the MA. Risk of bias was assessed using the Newcastle–Ottawa Scale.
The qualitative review suggested increased cognitive decline following AIH, but several reports were particularly vulnerable to bias. Domain-specific outcomes following AIH included declines in memory and processing speed. Increasing age and the severity of illness were the most consistent risk factors for PHCD. PHCD was supported by MA of seven eligible studies with 41,453 participants (Cohen’s d = −0.25, 95% CI [−0.02, −0.49] I2 35%).
There is preliminary evidence that AIH exposure accelerates or triggers cognitive decline in the elderly patient. PHCD reported in specific contexts could be subsets of a larger phenomenon and caused by overlapping mechanisms. Future research must clarify the trajectory, clinical significance, and etiology of PHCD: a priority in the face of an aging population with increasing rates of both cognitive impairment and hospitalization.
To characterize associations between exposures within and outside the medical workplace with healthcare personnel (HCP) SARS-CoV-2 infection, including the effect of various forms of respiratory protection.
We collected data from international participants via an online survey.
In total, 1,130 HCP (244 cases with laboratory-confirmed COVID-19, and 886 controls healthy throughout the pandemic) from 67 countries not meeting prespecified exclusion (ie, healthy but not working, missing workplace exposure data, COVID symptoms without lab confirmation) were included in this study.
Respondents were queried regarding workplace exposures, respiratory protection, and extra-occupational activities. Odds ratios for HCP infection were calculated using multivariable logistic regression and sensitivity analyses controlling for confounders and known biases.
HCP infection was associated with non–aerosol-generating contact with COVID-19 patients (adjusted OR, 1.4; 95% CI, 1.04–1.9; P = .03) and extra-occupational exposures including gatherings of ≥10 people, patronizing restaurants or bars, and public transportation (adjusted OR range, 3.1–16.2). Respirator use during aerosol-generating procedures (AGPs) was associated with lower odds of HCP infection (adjusted OR, 0.4; 95% CI, 0.2–0.8, P = .005), as was exposure to intensive care and dedicated COVID units, negative pressure rooms, and personal protective equipment (PPE) observers (adjusted OR range, 0.4–0.7).
COVID-19 transmission to HCP was associated with medical exposures currently considered lower-risk and multiple extra-occupational exposures, and exposures associated with proper use of appropriate PPE were protective. Closer scrutiny of infection control measures surrounding healthcare activities and medical settings considered lower risk, and continued awareness of the risks of public congregation, may reduce the incidence of HCP infection.
Bipolar disorder (BD) is a familial psychiatric disorder associated with frontotemporal and subcortical brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about structural brain trajectories in those at risk.
Neuroimaging was conducted at baseline and at 2-year follow-up interval in 90 high-risk individuals with a first-degree BD relative (HR), and 56 participants with no family history of mental illness who could have non-BD diagnoses. All 146 subjects were aged 12–30 years at baseline. We examined longitudinal change in gray and white matter volume, cortical thickness, and surface area in the frontotemporal cortex and subcortical regions.
Compared to controls, HR participants showed accelerated cortical thinning and volume reduction in right lateralised frontal regions, including the inferior frontal gyrus, lateral orbitofrontal cortex, frontal pole and rostral middle frontal gyrus. Independent of time, the HR group had greater cortical thickness in the left caudal anterior cingulate cortex, larger volume in the right medial orbitofrontal cortex and greater area of right accumbens, compared to controls. This pattern was evident even in those without the new onset of psychopathology during the inter-scan interval.
This study suggests that differences previously observed in BD are developing prior to the onset of the disorder. The pattern of pathological acceleration of cortical thinning is likely consistent with a disturbance of molecular mechanisms responsible for normal cortical thinning. We also demonstrate that neuroanatomical differences in HR individuals may be progressive in some regions and stable in others.
Air pollution is linked to mortality and morbidity. Since humans spend nearly all their time indoors, improving indoor air quality (IAQ) is a compelling approach to mitigate air pollutant exposure. To assess interventions, relying on clinical outcomes may require prolonged follow-up, which hinders feasibility. Thus, identifying biomarkers that respond to changes in IAQ may be useful to assess the effectiveness of interventions.
We conducted a narrative review by searching several databases to identify studies published over the last decade that measured the response of blood, urine, and/or salivary biomarkers to variations (natural and intervention-induced) of changes in indoor air pollutant exposure.
Numerous studies reported on associations between IAQ exposures and biomarkers with heterogeneity across study designs and methods. This review summarizes the responses of 113 biomarkers described in 30 articles. The biomarkers which most frequently responded to variations in indoor air pollutant exposures were high sensitivity C-reactive protein (hsCRP), von Willebrand Factor (vWF), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 1-hydroxypyrene (1-OHP).
This review will guide the selection of biomarkers for translational studies evaluating the impact of indoor air pollutants on human health.
Whether unintentional or by design, built, social, and perceived environments influence the human experience. Behavior is not solely the product of a rational motivated actor, operating independently from his or her environment; rather, it is also a function of edifices, neighborhoods, and public spaces, as well as the inhabitants, community norms, and the social capital they generate. Likewise, addictive behaviors have as much to do with the environmental contexts surrounding individuals as with their unique biological factors, specific brain mechanisms, and psychogenic causes. Any attempt to address addiction at either individual or population levels would benefit from careful consideration of the social and contextual influences on cognitions, opportunities, motivations, and behaviors. Interventions informed by this understanding are more likely to be efficacious than those solely targeted toward individual biology, motivations, or attitudes. In this chapter, we discuss the relationship between physical and social environments (PSE), health, and the behavior of humans. We then focus on the influential role of the PSE on the consumption of alcohol, tobacco, and other substances; food, eating behaviors, and addictions contributing to the current obesity epidemic; and a selection of other behavioral addictions. The chapter closes by discussing methodological considerations and implications for professional practice.
The emphasis on team science in clinical and translational research increases the importance of collaborative biostatisticians (CBs) in healthcare. Adequate training and development of CBs ensure appropriate conduct of robust and meaningful research and, therefore, should be considered as a high-priority focus for biostatistics groups. Comprehensive training enhances clinical and translational research by facilitating more productive and efficient collaborations. While many graduate programs in Biostatistics and Epidemiology include training in research collaboration, it is often limited in scope and duration. Therefore, additional training is often required once a CB is hired into a full-time position. This article presents a comprehensive CB training strategy that can be adapted to any collaborative biostatistics group. This strategy follows a roadmap of the biostatistics collaboration process, which is also presented. A TIE approach (Teach the necessary skills, monitor the Implementation of these skills, and Evaluate the proficiency of these skills) was developed to support the adoption of key principles. The training strategy also incorporates a “train the trainer” approach to enable CBs who have successfully completed training to train new staff or faculty.
A non-GMO trait called Inzen™ was recently commercialized in grain sorghum to combat weedy grasses, allowing the use of nicosulfuron POST in the crop. Inzen™ grain sorghum carries a double mutation in the acetolactate synthase (ALS) gene Val560Ile and Trp574Leu, which potentially results in cross-resistance to a wide assortment of ALS-inhibiting herbicides. To evaluate the scope of cross-resistance to Weed Science Society of America Group 2 herbicides in addition to nicosulfuron, tests were conducted in 2016 and 2017 at the Lon Mann Cotton Research Station near Marianna, AR, the Arkansas Agricultural Research and Extension Center in Fayetteville, AR, and in 2016 at the Pine Tree Research Station near Colt, AR. The tests included ALS-inhibiting herbicides from all five families: sulfonylureas, imidazolinones, pyrimidinylthiobenzoics, triazolinones, and triazolopyrimidines. Treatments were made PRE or POST to grain sorghum at a 1× rate for crops in which each herbicide is labeled. Grain sorghum planted in the PRE trial were Inzen™ and a conventional cultivar. Visible estimates of injury and sorghum heights were recorded at 2 and 4 wk after herbicide application, and yield data were collected at crop maturity. In the PRE trial, no visible injury, sorghum height reduction, or yield loss were observed in plots containing the Inzen™ cultivar. Applications made POST to the Inzen™ grain sorghum caused visible injury, sorghum height reduction, and yield loss of 20%, 13%, and 35%, respectively, only in plots where bispyribac-Na was applied. There was no impact on the crop from other POST-applied ALS-inhibiting herbicides. These results demonstrate that the Inzen™ trait confers cross-resistance to most ALS-inhibiting herbicides and could offer promising new alternatives for weed control and protection from carryover of residual ALS-inhibiting herbicides in grain sorghum.
Cohorting patients who are colonized or infected with multidrug-resistant organisms (MDROs) protects uncolonized patients from acquiring MDROs in healthcare settings. The potential for cross transmission within the cohort and the possibility of colonized patients acquiring secondary isolates with additional antibiotic resistance traits is often neglected. We searched for evidence of cross transmission of KPC+ Klebsiella pneumoniae (KPC-Kp) colonization among cohorted patients in a long-term acute-care hospital (LTACH), and we evaluated the impact of secondary acquisitions on resistance potential.
Genomic epidemiological investigation.
A high-prevalence LTACH during a bundled intervention that included cohorting KPC-Kp–positive patients.
Whole-genome sequencing (WGS) and location data were analyzed to identify potential cases of cross transmission between cohorted patients.
Secondary KPC-Kp isolates from 19 of 28 admission-positive patients were more closely related to another patient’s isolate than to their own admission isolate. Of these 19 cases, 14 showed strong genomic evidence for cross transmission (<10 single nucleotide variants or SNVs), and most of these patients occupied shared cohort floors (12 patients) or rooms (4 patients) at the same time. Of the 14 patients with strong genomic evidence of acquisition, 12 acquired antibiotic resistance genes not found in their primary isolates.
Acquisition of secondary KPC-Kp isolates carrying distinct antibiotic resistance genes was detected in nearly half of cohorted patients. These results highlight the importance of healthcare provider adherence to infection prevention protocols within cohort locations, and they indicate the need for future studies to assess whether multiple-strain acquisition increases risk of adverse patient outcomes.
This chapter provides a wide-ranging review of the clinical pharmacology of drugs for the treatment of schizophrenia and psychosis other than clozapine. These are dopamine receptor antagonists and dopamine partial agonists (as per the new Neuroscience-based Nomenclature (NbN) classification). This chapter covers their pharmacodynamics, pharmacokinetics, adverse effects, the latest evidence regarding their ‘antipsychotic’ mechanism of action, their use in the acute and maintenance treatment of schizophrenia, other therapeutic indications and some controversies that surround their use.
Dopamine receptor antagonists and dopamine partial agonists are commonly referred to as antipsychotics. As a clinical shorthand the term ‘antipsychotic’ is likely to remain in use.
According to the stress inoculation hypothesis, successfully navigating life stressors may improve one's ability to cope with subsequent stressors, thereby increasing psychiatric resilience.
Among individuals with no baseline history of post-traumatic stress disorder (PTSD) and/or major depressive disorder (MDD), to determine whether a history of a stressful life event protected participants against the development of PTSD and/or MDD after a natural disaster.
Analyses utilised data from a multiwave, prospective cohort study of adult Chilean primary care attendees (years 2003–2011; n = 1160). At baseline, participants completed the Composite International Diagnostic Interview (CIDI), a comprehensive psychiatric diagnostic instrument, and the List of Threatening Experiences, a 12-item questionnaire that measures major stressful life events. During the study (2010), the sixth most powerful earthquake on record struck Chile. One year later (2011), the CIDI was re-administered to assess post-disaster PTSD and/or MDD.
Marginal structural logistic regressions indicated that for every one-unit increase in the number of pre-disaster stressors, the odds of developing post-disaster PTSD or MDD increased (OR = 1.21, 95% CI 1.08–1.37, and OR = 1.16, 95% CI 1.06–1.27 respectively). When categorising pre-disaster stressors, individuals with four or more stressors (compared with no stressors) had higher odds of developing post-disaster PTSD (OR = 2.77, 95% CI 1.52–5.04), and a dose–response relationship between pre-disaster stressors and post-disaster MDD was found.
In contrast to the stress inoculation hypothesis, results indicated that experiencing multiple stressors increased the vulnerability to developing PTSD and/or MDD after a natural disaster. Increased knowledge regarding the individual variations of these disorders is essential to inform targeted mental health interventions after a natural disaster, especially in under-studied populations.
Unit cohesion may protect service member mental health by mitigating effects of combat exposure; however, questions remain about the origins of potential stress-buffering effects. We examined buffering effects associated with two forms of unit cohesion (peer-oriented horizontal cohesion and subordinate-leader vertical cohesion) defined as either individual-level or aggregated unit-level variables.
Longitudinal survey data from US Army soldiers who deployed to Afghanistan in 2012 were analyzed using mixed-effects regression. Models evaluated individual- and unit-level interaction effects of combat exposure and cohesion during deployment on symptoms of post-traumatic stress disorder (PTSD), depression, and suicidal ideation reported at 3 months post-deployment (model n's = 6684 to 6826). Given the small effective sample size (k = 89), the significance of unit-level interactions was evaluated at a 90% confidence level.
At the individual-level, buffering effects of horizontal cohesion were found for PTSD symptoms [B = −0.11, 95% CI (−0.18 to −0.04), p < 0.01] and depressive symptoms [B = −0.06, 95% CI (−0.10 to −0.01), p < 0.05]; while a buffering effect of vertical cohesion was observed for PTSD symptoms only [B = −0.03, 95% CI (−0.06 to −0.0001), p < 0.05]. At the unit-level, buffering effects of horizontal (but not vertical) cohesion were observed for PTSD symptoms [B = −0.91, 90% CI (−1.70 to −0.11), p = 0.06], depressive symptoms [B = −0.83, 90% CI (−1.24 to −0.41), p < 0.01], and suicidal ideation [B = −0.32, 90% CI (−0.62 to −0.01), p = 0.08].
Policies and interventions that enhance horizontal cohesion may protect combat-exposed units against post-deployment mental health problems. Efforts to support individual soldiers who report low levels of horizontal or vertical cohesion may also yield mental health benefits.