An Introduction to the Complete Blood Count for Clinical Chemists: Red Blood Cells.

BACKGROUND: The most frequently ordered laboratory test worldwide is the complete blood count (CBC). CONTENT: In this primer, the red blood cell test components of the CBC are introduced, followed by a discussion of the laboratory evaluation of anemia and polycythemia. SUMMARY: As clinical chemists are increasingly tasked to direct laboratories outside of the traditional clinical chemistry sections such as hematology, expertise must be developed. This review article is a dedication to that effort.

Atmospheric isoprene measurements reveal larger-than-expected Southern Ocean emissions.

Isoprene is a key trace component of the atmosphere emitted by vegetation and other organisms. It is highly reactive and can impact atmospheric composition and climate by affecting the greenhouse gases ozone and methane and secondary organic aerosol formation. Marine fluxes are poorly constrained due to the paucity of long-term measurements; this in turn limits our understanding of isoprene cycling in the ocean. Here we present the analysis of isoprene concentrations in the atmosphere measured across the Southern Ocean over 4 months in the summertime. Some of the highest concentrations ( >500 ppt) originated from the marginal ice zone in the Ross and Amundsen seas, indicating the marginal ice zone is a significant source of isoprene at high latitudes. Using the United Kingdom Earth System Model we show that current estimates of sea-to-air isoprene fluxes underestimate observed isoprene by a factor >20. A daytime source of isoprene is required to reconcile models with observations. The model presented here suggests such an increase in isoprene emissions would lead to >8% decrease in the hydroxyl radical in regions of the Southern Ocean, with implications for our understanding of atmospheric oxidation and composition in remote environments, often used as proxies for the pre-industrial atmosphere.

An Introduction to the Complete Blood Count for Clinical Chemists: Platelets.

BACKGROUND: The most ordered laboratory test worldwide is the complete blood count (CBC). CONTENT: In this primer, an introduction to platelet testing in the context of the CBC is provided with a discussion of the laboratory evaluation of platelet abnormalities including thrombocytopenia and thrombocytosis. SUMMARY: As clinical chemists continue to be tasked to direct laboratories outside of the traditional clinical chemistry sections such as hematology, expertise must be developed. This primer is dedicated to that effort.

ComBating inter-site differences in field strength: harmonizing preclinical traumatic brain injury MRI data.

Integrating datasets from multiple sites and scanners can increase statistical power for neuroimaging studies but can also introduce significant inter-site confounds. We evaluated the effectiveness of ComBat, an empirical Bayes approach, to combine longitudinal preclinical MRI data acquired at 4.7 or 9.4 T at two different sites in Australia. Male Sprague Dawley rats underwent MRI on Days 2, 9, 28, and 150 following moderate/severe traumatic brain injury (TBI) or sham injury as part of Project 1 of the NIH/NINDS-funded Centre Without Walls EpiBioS4Rx project. Diffusion-weighted and multiple-gradient-echo images were acquired, and outcomes included QSM, FA, and ADC. Acute injury measures including apnea and self-righting reflex were consistent between sites. Mixed-effect analysis of ipsilateral and contralateral corpus callosum (CC) summary values revealed a significant effect of site on FA and ADC values, which was removed following ComBat harmonization. Bland-Altman plots for each metric showed reduced variability across sites following ComBat harmonization, including for QSM, despite appearing to be largely unaffected by inter-site differences and no effect of site observed. Following harmonization, the combined inter-site data revealed significant differences in the imaging metrics consistent with previously reported outcomes. TBI resulted in significantly reduced FA and increased susceptibility in the ipsilateral CC, and significantly reduced FA in the contralateral CC compared with sham-injured rats. Additionally, TBI rats also exhibited a reversal in ipsilateral CC ADC values over time with significantly reduced ADC at Day 9, followed by increased ADC 150 days after injury. Our findings demonstrate the need for harmonizing multi-site preclinical MRI data and show that this can be successfully achieved using ComBat while preserving phenotypical changes due to TBI.

Effectiveness of Interventions Promoting Dietary Intake, Physical Activity, and Healthy Weight Status of Children in Family Child Care: A Systematic Review.

INTRODUCTION: This systematic review examines the effectiveness of interventions in family child care (FCC) on (1) children's dietary intake, physical activity levels and weight, and (2) FCC health-promoting environments, policies, and practices. Quasi-experimental studies measuring these outcomes were included. METHODS: All available articles up to July 2023 were searched using MEDLINE, ERIC, CINAHL, Embase, Scopus, and A+ Education, and 15 interventions were included. Methodological quality was assessed with the Effective Public Health Practice Project Assessment tool. RESULTS: Thirteen studies were weak, and 2 strong in quality. Four interventions included children's dietary intake as an outcome measure, 2 included physical activity, and 3 weight status. Twelve interventions assessed nutrition and 7 physical activity environmental outcomes. DISCUSSION: Interventions in FCC improved children's dietary intake, but their impact on physical activity and weight status was inconclusive. Furthermore, positive impacts were observed in environmental outcomes related to nutrition, whereas research on physical activity environmental outcomes was limited. IMPLICATIONS FOR RESEARCH AND PRACTICE: Future research could replicate interventions to validate effectiveness and understand positive outcome mechanisms. Future interventions might use FCC stakeholders' input, incorporate innovative physical activity components, enhance FCC providers' position as role models, involve parents, and target those groups that are at a high risk of being obese.

What methods are used to examine representation of mental ill-health on social media? A systematic review.

There has been an increasing number of papers which explore the representation of mental health on social media using various social media platforms and methodologies. It is timely to review methodologies employed in this growing body of research in order to understand their strengths and weaknesses. This systematic literature review provides a comprehensive overview and evaluation of the methods used to investigate the representation of mental ill-health on social media, shedding light on the current state of this field. Seven databases were searched with keywords related to social media, mental health, and aspects of representation (e.g., trivialisation or stigma). Of the 36 studies which met inclusion criteria, the most frequently selected social media platforms for data collection were Twitter (n = 22, 61.1%), Sina Weibo (n = 5, 13.9%) and YouTube (n = 4, 11.1%). The vast majority of studies analysed social media data using manual content analysis (n = 24, 66.7%), with limited studies employing more contemporary data analysis techniques, such as machine learning (n = 5, 13.9%). Few studies analysed visual data (n = 7, 19.4%). To enable a more complete understanding of mental ill-health representation on social media, further research is needed focussing on popular and influential image and video-based platforms, moving beyond text-based data like Twitter. Future research in this field should also employ a combination of both manual and computer-assisted approaches for analysis.

The use of andexanet alfa vs. 4-factor prothrombin complex concentrates in the setting of life-threatening intracranial hemorrhage.

OBJECTIVE: Andexanet alfa is a targeted reversal agent for life threatening hemorrhage associated with direct acting oral anticoagulants (DOACs), but there is uncertainty regarding the benefit when compared to 4-factor prothrombin complex concentrate (4F-PCC) for this indication. We investigated the clinical outcomes and cost associated with reversal of DOACs in the setting of life-threatening intracranial hemorrhage (ICH). METHODS: A retrospective evaluation was conducted to evaluate patients with ICH in the setting of anticoagulation with DOAC from 9/1/2013 to 4/30/2020. Patients were included in the study if they received reversal with either andexanet alfa or 4F-PCC. RESULTS: Eighty-nine patients were included in the study. There was no statistically significant difference in 30-day mortality between patients who received andexanet alfa or 4F-PCC (52% vs. 35%, P  = 0.14). Radiographic stability of bleed was identified in 57% of patients receiving andexanet alfa vs. 58% of patients receiving 4F-PCC ( P  = 0.93). Median length of stay was not different between the andexanet alfa and 4F-PCC populations (7 days [IQR 6 - 12] vs. 6 days [IQR 3-12], P  = 0.66). Median cost of reversal agent was higher in patients receiving andexanet alfa compared to 4F-PCC ($15 000 [IQR 15 000-$27 000] vs. $11 650 [IQR $8567-$14 149]). CONCLUSION: Among patients with life-threatening intracranial hemorrhage in the setting of DOAC therapy, no clinical differences were observed with respect to selection of reversal agent. Prothrombin complex concentrates remain a viable alternative to reversal of DOAC therapy though multicenter, randomized, prospective studies are needed to further evaluate the role of 4F-PCC in the reversal of DOAC therapy.

Investigating socio-ecological factors influencing implementation of tuberculosis infection prevention and control in rural Papua New Guinea.

BACKGROUND: Tuberculosis (TB) is a highly transmissible infectious disease killing millions of people yearly, particularly in low-income countries. TB is most likely to be transmitted in healthcare settings with poor infection control practices. Implementing TB infection prevention and control (TB-IPC) is pivotal to preventing TB transmission in healthcare settings. This study investigated diverse stakeholders' perspectives relating to barriers and strategies for TB-IPC in rural hospitals in Papua New Guinea. METHODS: Multiple qualitative case studies were conducted with 32 key stakeholders with experience in TB services. Data collection drew on three primary sources to triangulate data: semi-structured interviews, document reviews and field notes. The data were analyzed using hybrid deductive-inductive thematic analysis. RESULTS: Our results reveal that key stakeholders perceive multiple interdependent factors that affect TB-IPC practice. The key emerging themes include strategic planning for and prioritizing TB-IPC guidelines; governance, leadership and accountability at the provincial level; community attitudes towards TB control; institutional capacity to deliver TB care, healthcare workers' safety, and long-term partnership and integration of TB-IPC programmes into the broad IPC programme. CONCLUSIONS: The evidence suggests that a multi-perspective approach is crucial for TB-IPC guidelines in healthcare institutions. Interventions focusing on addressing health systems strengthening may improve the implementation of TB-IPC guidelines.

Epilepsy phenotype and its reproducibility after lateral fluid percussion-induced traumatic brain injury in rats: Multicenter EpiBioS4Rx study project 1.

OBJECTIVE: This study was undertaken to assess reproducibility of the epilepsy outcome and phenotype in a lateral fluid percussion model of posttraumatic epilepsy (PTE) across three study sites. METHODS: A total of 525 adult male Sprague Dawley rats were randomized to lateral fluid percussion-induced brain injury (FPI) or sham operation. Of these, 264 were assigned to magnetic resonance imaging (MRI cohort, 43 sham, 221 traumatic brain injury [TBI]) and 261 to electrophysiological follow-up (EEG cohort, 41 sham, 220 TBI). A major effort was made to harmonize the rats, materials, equipment, procedures, and monitoring systems. On the 7th post-TBI month, rats were video-EEG monitored for epilepsy diagnosis. RESULTS: A total of 245 rats were video-EEG phenotyped for epilepsy on the 7th postinjury month (121 in MRI cohort, 124 in EEG cohort). In the whole cohort (n = 245), the prevalence of PTE in rats with TBI was 22%, being 27% in the MRI and 18% in the EEG cohort (p > .05). Prevalence of PTE did not differ between the three study sites (p > .05). The average seizure frequency was .317 ± .725 seizures/day at University of Eastern Finland (UEF; Finland), .085 ± .067 at Monash University (Monash; Australia), and .299 ± .266 at University of California, Los Angeles (UCLA; USA; p < .01 as compared to Monash). The average seizure duration did not differ between UEF (104 ± 48 s), Monash (90 ± 33 s), and UCLA (105 ± 473 s; p > .05). Of the 219 seizures, 53% occurred as part of a seizure cluster (≥3 seizures/24 h; p >.05 between the study sites). Of the 209 seizures, 56% occurred during lights-on period and 44% during lights-off period (p > .05 between the study sites). SIGNIFICANCE: The PTE phenotype induced by lateral FPI is reproducible in a multicenter design. Our study supports the feasibility of performing preclinical multicenter trials in PTE to increase statistical power and experimental rigor to produce clinically translatable data to combat epileptogenesis after TBI.

Successful harmonization in EpiBioS4Rx biomarker study on post-traumatic epilepsy paves the way towards powered preclinical multicenter studies.

OBJECTIVE: Project 1 of the Preclinical Multicenter Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) consortium aims to identify preclinical biomarkers for antiepileptogenic therapies following traumatic brain injury (TBI). The international participating centers in Finland, Australia, and the United States have made a concerted effort to ensure protocol harmonization. Here, we evaluate the success of harmonization process by assessing the timing, coverage, and performance between the study sites. METHOD: We collected data on animal housing conditions, lateral fluid-percussion injury model production, postoperative care, mortality, post-TBI physiological monitoring, timing of blood sampling and quality, MR imaging timing and protocols, and duration of video-electroencephalography (EEG) follow-up using common data elements. Learning effect in harmonization was assessed by comparing procedural accuracy between the early and late stages of the project. RESULTS: The animal housing conditions were comparable between the study sites but the postoperative care procedures varied. Impact pressure, duration of apnea, righting reflex, and acute mortality differed between the study sites (p < 0.001). The severity of TBI on D2 post TBI assessed using the composite neuroscore test was similar between the sites, but recovery of acute somato-motor deficits varied (p < 0.001). A total of 99% of rats included in the final cohort in UEF, 100% in Monash, and 79% in UCLA had blood samples taken at all time points. The timing of sampling differed on day (D)2 (p < 0.05) but not D9 (p > 0.05). Plasma quality was poor in 4% of the samples in UEF, 1% in Monash and 14% in UCLA. More than 97% of the final cohort were MR imaged at all timepoints in all study sites. The timing of imaging did not differ on D2 and D9 (p > 0.05), but varied at D30, 5 months, and ex vivo timepoints (p < 0.001). The percentage of rats that completed the monthly high-density video-EEG follow-up and the duration of video-EEG recording on the 7th post-injury month used for seizure detection for diagnosis of post-traumatic epilepsy differed between the sites (p < 0.001), yet the prevalence of PTE (UEF 21%, Monash 22%, UCLA 23%) was comparable between the sites (p > 0.05). A decrease in acute mortality and increase in plasma quality across time reflected a learning effect in the TBI production and blood sampling protocols. SIGNIFICANCE: Our study is the first demonstration of the feasibility of protocol harmonization for performing powered preclinical multi-center trials for biomarker and therapy discovery of post-traumatic epilepsy.

Altering the Trajectory of Perfusion-Diffusion Deficits Using A BDNF Mimetic Acutely After TBI is Associated with Improved Functional Connectivity.

Traumatic brain injury (TBI) results in metabolic deficits and functionally compromised tissue. The BDNF mimetic R13 has a significant positive effect on both tissue metabolism and behavioral outcome after TBI, indicating a promising therapeutic. To understand the mechanism of action for this intervention, we determined whether there was any association between the underlying metabolic insult and any improvement in resting state functional connectivity (FC) with MRI, or whether R13 acts through mechanisms unrelated to metabolic recovery. We found perfusion deficits could be reasonably approximated by reductions in mean diffusivity (MD) acutely after injury, because a majority of regions with low perfusion matched to regions of low MD, indicative of cell swelling. Injury alone resulted in reduced cross-brain FC and contralateral hyperconnectivity at 1d compared to sham and these were spatially coincident with regions of low MD. R13 intervention at 1-7d altered the tissue trajectory of MD pathology away from pseudo-normalization so that a greater volume of tissue remained with low MD at 7d. These same regions were associated with significant changes in cross-brain and contralateral FC in R13 treated rats compared to injured vehicle-treated rats. These data indicate a likely metabolic effect of R13 acutely after injury.

A systematic review of the adolescent-directed marketing strategies of transnational fast food companies in low- and middle-income countries.

Introduction: Fast food consumption is associated with excessive intake of energy-dense foods; a major determinant of childhood obesity. The lack of data on the marketing strategies used to promote fast food to adolescents in low and middle-income countries (LMICs) acts as a barrier to global efforts to reduce the marketing of unhealthy foods to young people around the world. Objectives: This systematic review aimed to identify the adolescent-directed marketing strategies of transnational fast food corporations in LMICs. Methods: A systematic search of eight scientific databases (PubMed, CINAHL, Medline, Embase, ProQuest, PsycInfo, Scopus and Google Scholar) was conducted. Following PRISMA guidelines, primary research articles written in English were included if they were published between 1 January 2010 and 30 December 2022, and reported any adolescent-directed marketing activity undertaken by a transnational fast food company operating in a LMIC. Articles were excluded if they were not peer reviewed. The quality of the included articles was assessed using a condensed version of the Consolidated Criteria for Reporting Qualitative Research tool. Results: Twelve articles met the eligibility criteria and were included in this review. A narrative synthesis of these articles revealed that the most documented strategies used to promote fast food to adolescents in LMICs were the use of incentives or premium offers, product appeals, promotional characters and brand familiarity. These strategies were mostly observed on social media, suggesting that there are serious concerns about adolescent exposure to fast food via social media in developing settings, especially as contextual differences in the nature of such marketing were identified. Discussion: The promotion of fast food to adolescents in LMICs is contextual in nature, with the nature of marketing strategies employed by transnational fast food corporations varying greatly across cultural and socio-economic contexts. These findings are crucial for the development of guidelines and regulations restricting the marketing of fast food to adolescents in lower income settings, contributing to global efforts to reduce adolescent exposure to unhealthy food promotion.

Iron Biology - An Overview for Laboratorians.

Iron serves a critical role in many metabolic processes, including oxygen delivery (e.g., hemoglobin) and oxygen utilization for the generation of ATP (e.g., cytochromes). Disorders of iron metabolism are best recognized and evaluated in the context of iron's absorption, transportation, monitoring, cellular uptake, and recycling. This review highlights these processes so that disorders of iron deficiency and iron excess can be better understood. Key players in iron metabolism will be highlighted, such as hepcidin, ferroportin, erythroferrone, transferrin, ferritin, HFE, and the transferrin receptors.

Image data harmonization tools for the analysis of post-traumatic epilepsy development in preclinical multisite MRI studies.

Preclinical MRI studies have been utilized for the discovery of biomarkers that predict post-traumatic epilepsy (PTE). However, these single site studies often lack statistical power due to limited and homogeneous datasets. Therefore, multisite studies, such as the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx), are developed to create large, heterogeneous datasets that can lead to more statistically significant results. EpiBioS4Rx collects preclinical data internationally across sites, including the United States, Finland, and Australia. However, in doing so, there are robust normalization and harmonization processes that are required to obtain statistically significant and generalizable results. This work describes the tools and procedures used to harmonize multisite, multimodal preclinical imaging data acquired by EpiBioS4Rx. There were four main harmonization processes that were utilized, including file format harmonization, naming convention harmonization, image coordinate system harmonization, and diffusion tensor imaging (DTI) metrics harmonization. By using Python tools and bash scripts, the file formats, file names, and image coordinate systems are harmonized across all the sites. To harmonize DTI metrics, values are estimated for each voxel in an image to generate a histogram representing the whole image. Then, the Quantitative Imaging Toolkit (QIT) modules are utilized to scale the mode to a value of one and depict the subsequent harmonized histogram. The standardization of file formats, naming conventions, coordinate systems, and DTI metrics are qualitatively assessed. The histograms of the DTI metrics were generated for all the individual rodents per site. For inter-site analysis, an average of the individual scans was calculated to create a histogram that represents each site. In order to ensure the analysis can be run at the level of individual animals, the sham and TBI cohort were analyzed separately, which depicted the same harmonization factor. The results demonstrate that these processes qualitatively standardize the file formats, naming conventions, coordinate systems, and DTI metrics of the data. This assists in the ability to share data across the study, as well as disseminate tools that can help other researchers to strengthen the statistical power of their studies and analyze data more cohesively.

An Analysis of Crisis Communication Delivered by the Chief Health Officer During the COVID-19 Pandemic in Queensland, Australia.

During the first year of the COVID-19 pandemic, the state of Queensland, Australia, had relative success in containing viral transmission, presenting a unique case for potential insights into effective crisis management. Limited research exists into the communication style and effectiveness of Chief Health Officers (CHOs) throughout pandemic scenarios. Using an adapted Crisis Emergency and Risk Communication (CERC) framework based on 12 themes which indirectly assess domains of trust, credibility, transparency, and accountability. A content analysis of 107 press conferences dating from January 30th to December 24th, 2020 was conducted to analyze crisis communication style delivered by the Queensland CHO and guest speakers. Our analysis found that most communication aligned with the CERC framework, suggesting that adherence to CERC themes in crisis communication may have played an important role in the state's success. However, areas which were lacking included themes relating to efforts to address, search and gather knowledge. Analysis also revealed that some CERC themes overlapped or were missing, thus triggering the development of a modified framework to provide a more succinct coding model. Our findings demonstrate the importance communication plays in successful crisis management and the modified framework can be applied to analyze communication at national and sub-national levels.

Dysfibrinogenemia: discrepant results following infusion of purified fibrinogen.

Inherited dysfibrinogenemias are molecular disorders of fibrinogen that affect fibrin polymerization. The majority of cases are asymptomatic, but a significant proportion suffer from increased bleeding or thrombosis. We present two unrelated cases of dysfibrinogenemia, both of whom showed a characteristic discrepancy between fibrinogen activity and the immunologic fibrinogen. In one patient, the dysfibrinogenemia was confirmed by molecular analysis; in the other case, the diagnosis was presumptive based upon laboratory studies. Both patients underwent elective surgery. Both received a highly purified fibrinogen concentrate preoperatively and demonstrated a suboptimal laboratory response to the infusion. Three methods for determining fibrinogen concentration (Clauss fibrinogen, prothrombin-derived fibrinogen, and the viscoelastic functional fibrinogen) were utilized in the case of one patient, and these techniques showed discrepant results with the classic Clauss method giving the lowest concentration. Neither patient experienced excessive bleeding during surgery. Although these discrepancies have been previously described in untreated patients, their manifestation after infusion of purified fibrinogen is less well appreciated.

Validity of two weight prediction models for community-living patients participating in a weight loss program.

Models predicting individual body weights over time clarify patient expectations in weight loss programs. The accuracy of two commonly used weight prediction models in community living people is unclear. All eligible people entering a weight management program between 1992 and 2015 were included. Patients' diet was 1200 kcal/day for week 0 followed by 900 kcal/day for weeks 1-7 and were excluded from the analysis if they were nonadherent. We generated expected weights using the National Institutes of Health Body Weight Planner (NIH-BWP) and the Pennington Biomedical Research Center Weight Loss Predictor (PBRC-WLP). 3703 adherent people were included (mean age 46 years, 72.6% women, mean [SD] weight 262.3 pounds [54.2], mean [SD] BMI 42.4 [7.6]). Mean (SD) relative body weight differences (100*[observed-expected]/expected) for NIH-BWP and PBRC-WLP models was - 1.5% (3.8) and - 2.9% (3.2), respectively. At week 7, mean squared error with NIH-BWP (98.8, 83%CI 89.7-108.8) was significantly lower than that with PBRC-WLP (117.7, 83%CI 112.4-123.4). Notable variation in relative weight difference were seen (for NIH-BWP, 5th-95th percentile was - 6.2%, + 3.7%; Δ 9.9%). During the first 7 weeks of a weight loss program, both weight prediction models returned expected weights that were very close to observed values with the NIH-BWP being more accurate. However, notable variability between expected and observed weights in individual patients were seen. Clinicians can monitor patients in weight loss programs by comparing their progress with these data.