54 research outputs found
THE LAST PLANNER® SYSTEM PATH CLEARING APPROACH IN ACTION: A CASE STUDY
The “Last Planner® System” (LPS) is commonly viewed as the foundation of Lean Project Delivery. It is increasingly used in certain parts of the globe. However, LPS implementation often fades off due to issues reported at organisational, project and external levels. The LPS Path Clearing Approach (PCA) offers an antidote to these issues. The goal of this paper is to outline how the LPS-PCA helped restart a stalled implementation of the LPS through a “shallow and wide” organisational approach rather than a more traditional “narrow and deep” project approach. The LPS-PCA in action is documented within an on-going UK case study organisation. Action and covert research methods were used to introduce LPS principles, thinking and language without attributing them to LPS in response to resistance to the actual LPS. The 15 step actions within the LPS-PCA are expanded from a past, current and future state perspective. The study found that the LPS-PCA’s 15 step actions were useful as a benchmark to continuously remove constraints that blocked the implementation of the LPS. In summary, the use of the LPSPCA is recommended before, during and after organisations engage with LPS Consultants if organisations are serious about sustaining the implementation of the LPS
Community health workers identify children requiring health center admission in Northern Uganda: prehospital risk prediction using vital signs and advanced point-of-care tests
BackgroundOver five million children die annually from preventable and treatable illnesses. Most of these deaths occur in sub-Saharan Africa, predominantly in socioeconomically deprived regions. With nearly half of pediatric mortality occurring at the community level, serious illnesses must be detected early in the prehospital setting. The purpose of this 18-month, prospective, observational pilot study was to introduce the first use of the proinflammatory biomarker, CRP, in the prehospital setting to community health workers and to develop a prehospital predictive model to identify sick children requiring health center admission.MethodsWe recruited 636 children presenting to one of four community health worker teams who completed a prehospital evaluation and referred each child to the closest health center. The primary outcome for this study was admission at the health center for more than 24 h. We used logistic regression to quantify the area under the receiver operating characteristic curve (AUC).ResultsWe found poor discrimination of danger signs and CRP, with AUCs of 0.55 (95% CI 0.52-0.57) and 0.52 (95% CI 0.47-0.57), respectively. A model comprising vital signs demonstrated superior discrimination, with an AUC of 0.66 (95% CI 0.62-0.71), which improved with the addition of danger signs (AUC 0.69; 95% CI 0.64-0.73), and when restricted to children who tested negative for malaria (n = 327; AUC 0.71; 95% CI 0.65-0.77).ConclusionsWe demonstrate that performing advanced point-of-care tests is feasible in resource-limited community settings and present one of the first prehospital prediction models developed with community health workers
DAB2IP Loss in Luminal A Breast Cancer Leads to NF-kB Associated Aggressive Oncogenic Phenotypes
Despite proven therapy options for estrogen receptor (ER)-positive breast tumors, a substantial number of ER+ cancer patients exhibit relapse with associated metastasis. Loss of expression of RasGAPs leads to poor outcomes in several cancers, including breast cancer. Mining the TCGA breast cancer RNA-sequencing dataset revealed that low expression of the RasGAP DAB2IP was associated with a significant decrease in relapse-free survival in Luminal A breast cancer patients. Immunostaining demonstrated that DAB2IP loss occurred in grade 2 tumors and higher. Consistent with this, genes upregulated in DAB2IP-low Luminal A tumors were shared with more aggressive tumor subtypes and were associated with proliferation, metastasis, and altered ER signaling. Low DAB2IP expression in ER+ breast cancer cells was associated with increased proliferation, enhanced stemness phenotypes, and activation of IKK, the upstream regulator of the transcription factor NF-kB. Integrating cell-based ChIP-sequencing with motif analysis and TCGA RNA-seq data, we identified a set of candidate NF-kB target genes upregulated with loss of DAB2IP linked with several oncogenic phenotypes, including altered RNA processing. This study provides insight into mechanisms associated with aggressiveness and recurrence within a subset of the typically less aggressive Luminal A breast cancer intrinsic subtype
Obstetric and newborn outcomes of mothers with and without HIV infection in Anaka general hospital in Northern Uganda.
BackgroundWomen of reproductive age constitute a significant proportion of the global HIV burden, with millions becoming pregnant while on lifelong antiretroviral therapy (ART). Although ART has dramatically improved maternal and child health outcomes, concerns persist regarding its safety in pregnancy. This study compares obstetric and neonatal outcomes between women with and without HIV infection at Anaka General Hospital, a rural hospital in northern Uganda.MethodsA hospital-based retrospective cross-sectional study at Anaka General Hospital in northern Uganda was conducted from July 2020 to June 2023. A total of 914 delivery records were included, sampled using systematic random sampling from the hospital maternity register. Data were extracted from maternity and neonatal records using a structured tool. Associations between HIV status and obstetric or neonatal outcomes were assessed using Chi-square or Fisher's exact tests for categorical variables and independent sample t-tests for continuous variables. Multivariable logistic regression was used to adjust for potential confounders and a p ResultsOf the 914 participants included in the study 38 (4.2%) were HIV-positive. The odds of congenital anomalies were significantly higher among infants born to HIV-positive women compared with HIV-negative women (adjusted odds ratio = 9.76, 95% confidence interval: 1.72-55.48, p ConclusionHIV infection was significantly associated with an increased risk of congenital anomalies, while other obstetric and neonatal outcomes were similar between HIV-positive and HIV-negative women. We recommend enhanced prenatal monitoring and early fetal screening among HIV-positive pregnant women on dolutegravir-based ART. Additionally, prospective studies are needed to better understand the contribution of dolutegravir and maternal factors to congenital anomalies in HIV-exposed pregnancies
Metabolic differences between cold stored and machine perfused porcine kidneys::A 1H NMR based study
<sup>13</sup>C glucose labelling studies using 2D NMR are a useful tool for determining ex vivo whole organ metabolism during hypothermic machine perfusion of kidneys
BACKGROUND: The aim of this study is to determine the feasibility of using nuclear magnetic resonance (NMR) tracer studies ((13)C-enriched glucose) to detect ex vivo de novo metabolism in the perfusion fluid and cortical tissue of porcine kidneys during hypothermic machine perfusion (HMP). METHODS: Porcine kidneys (n = 6) were subjected to 24 h of HMP using the Organ Recovery Systems LifePort Kidney perfusion device. Glucose, uniformly enriched with the stable isotope (13)C ([U-(13)C] glucose), was incorporated into KPS-1-like perfusion fluid at a concentration of 10 mM. Analysis of perfusate was performed using both 1D (1)H and 2D (1)H,(13)C heteronuclear single quantum coherence (HSQC) NMR spectroscopy. The metabolic activity was then studied by quantifying the proportion of key metabolites containing (13)C in both perfusate and tissue samples. RESULTS: There was significant enrichment of (13)C in a number of central metabolites present in both the perfusate and tissue extracts and was most pronounced for lactate and alanine. The total amount of enriched lactate (per sample) in perfusion fluid increased during HMP (31.1 ± 12.2 nmol at 6 h vs 93.4 ± 25.6 nmol at 24 h p < 0.01). The total amount of enriched alanine increased in a similar fashion (1.73 ± 0.89 nmol at 6 h vs 6.80 ± 2.56 nmol at 24 h p < 0.05). In addition, small amounts of enriched acetate and glutamic acid were evident in some samples. CONCLUSIONS: This study conclusively demonstrates that de novo metabolism occurs during HMP and highlights active metabolic pathways in this hypothermic, hypoxic environment. Whilst the majority of the (13)C-enriched glucose is metabolised into glycolytic endpoint metabolites such as lactate, the presence of non-glycolytic pathway derivatives suggests that metabolism during HMP is more complex than previously thought. Isotopic labelled ex vivo organ perfusion studies using 2D NMR are feasible and informative
Recommended from our members
Promotoras Frente a la Obesidad Infantil: An Innovative Participatory Research Program Development Model
In-Press Manuscript
Sage Ope
Recommended from our members
Community Health Workers Identify Seriously Ill Children in Northern Uganda: Prehospital Risk Prediction using Vital Signs and Advanced Point-of-Care Tests
Raw data for this project used to develop risk prediction mode
Voices of the Volunteer Health Workforce: Understanding Motivation and Barriers Among Community Health Workers in Pader District, Uganda
- …
