An example of requirements for Advanced Subsonic Civil Transport (ASCT) flight control system using structured techniques

The requirements are presented for an Advanced Subsonic Civil Transport (ASCT) flight control system generated using structured techniques. The requirements definition starts from initially performing a mission analysis to identify the high level control system requirements and functions necessary to satisfy the mission flight. The result of the study is an example set of control system requirements partially represented using a derivative of Yourdon's structured techniques. Also provided is a research focus for studying structured design methodologies and in particular design-for-validation philosophies

The relationship between tumour glucose metabolism and host systemic inflammatory responses in patients with cancer: a systematic review

One of the most important and long recognised characteristics of tumour cells is their dysregulated cellular energetics with anaerobic driven glucose uptake. In patients with cancer the prognostic value of the systemic inflammatory response has been well established and the recent combination of PET and CT scanning combines the assessment of tumour physiological activity with detailed anatomical localisation. The aim of this study was to carry out a systematic review of the assessment of the relationship between both the tumour and host inflammatory responses using PETCT. An extensive literature review using targeted subject headings was carried out in the US National Library of Medicine, the Excerpta Medica database and Cochrane Database of Systematic Reviews until the 31st March 2018. On completion of the online search, the title and abstracts of each identified study was examined for relevance. Studies with duplicate datasets, not available in English and that did not have full text availability were excluded. Full texts of relevant articles were obtained and were then examined to identify any further relevant articles. Twelve studies containing 2,588 patients were included in the final analysis. All of the included studies used the FDG tracer in PETCT imaging and had biochemical assessment of the systemic inflammatory response. The majority of studies showed a direct relationship between the tumour and bone marrow glucose uptake and host systemic inflammatory responses as measured by C-Reactive Protein (CRP) ( = 2), albumin ( = 2), White Cell Count (WCC) ( = 3), neutrophils ( = 2) and platelets ( = 2). The majority of the studies ( = 8) also showed a direct relationship between tumour and bone marrow glucose uptake and poor outcomes. This review suggests a direct relationship between the tumour and bone marrow glucose uptake and host systemic inflammation. This may suggest new approaches for more optimal therapeutic targeting and monitoring strategies in patients with cancer

Advances in Public Health Accreditation Readiness and Quality Improvement: Evaluation Findings From the National Public Health Improvement Initiative

Continuous quality improvement is a central tenet of the Public Health Accreditation Board’s (PHAB) national voluntary public health accreditation program. Similarly, the Centers for Disease Control and Prevention launched the National Public Health Improvement Initiative (NPHII) in 2010 with the goal of advancing accreditation readiness, performance management, and quality improvement (QI)

PACAP-38 induces neuronal differentiation of human SH-SY5Y neuroblastoma cells via cAMP-mediated activation of ERK and p38 MAP kinases1

The intracellular signaling pathways mediating the neurotrophic actions of pituitary adenylate cyclase-activating polypeptide (PACAP) were investigated in human neuroblastoma SH-SY5Y cells. Previously, we showed that SH-SY5Y cells express the PAC1 and VIP/PACAP receptor type 2 (VPAC2) receptors, and that the robust cAMP production in response to PACAP and vasoactive intestinal peptide (VIP) was mediated by PAC1 receptors (Lutz et al. 2006). Here, we investigated the ability of PACAP-38 to differentiate SH-SY5Y cells by measuring morphological changes and the expression of neuronal markers. PACAP-38 caused a concentration-dependent increase in the number of neurite-bearing cells and an up-regulation in the expression of the neuronal proteins Bcl-2, growth-associated protein-43 (GAP-43) and choline acetyltransferase: VIP was less effective than PACAP-38 and the VPAC2 receptor-specific agonist, Ro 25-1553, had no effect. The effects of PACAP-38 and VIP were blocked by the PAC1 receptor antagonist, PACAP6-38. As observed with PACAP-38, the adenylyl cyclase activator, forskolin, also induced an increase in the number of neurite-bearing cells and an up-regulation in the expression of Bcl-2 and GAP-43. PACAP-induced differentiation was prevented by the adenylyl cyclase inhibitor, 2′,5′-dideoxyadenosine (DDA), but not the protein kinase A (PKA) inhibitor, H89, or by siRNA-mediated knock-down of the PKA catalytic subunit. PACAP-38 and forskolin stimulated the activation of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAP; p38 MAP kinase) and c-Jun N-terminal kinase (JNK). PACAP-induced neuritogenesis was blocked by the MEK1 inhibitor PD98059 and partially by the p38 MAP kinase inhibitor SB203580. Activation of exchange protein directly activated by cAMP (Epac) partially mimicked the effects of PACAP-38, and led to the phosphorylation of ERK but not p38 MAP kinase. These results provide evidence that the neurotrophic effects of PACAP-38 on human SH-SY5Y neuroblastoma cells are mediated by the PAC1 receptor through a cAMP-dependent but PKA-independent mechanism, and furthermore suggest that this involves Epac-dependent activation of ERK as well as activation of the p38 MAP kinase signaling pathway

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression.

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe

Fit for an emperor: Akbar’s luxury manuscript of the Baharistan of Jami and its conservation

This paper discusses the conservation treatment and technical study of an exquisitely decorated copy of the Baharistan of Jami, produced c. 1595 for the Mughal emperor Akbar. 19th century repairs and rebinding had contributed to a deteriorating condition, rendering it inaccessible. In order to anticipate how conservation interventions might affect the manuscript’s visual appearance and evidence of material history it was necessary to undertake a technical study, followed by a comparison with two other Akbari manuscripts. These studies informed the methods chosen to conserve the manuscript and return it to an accessible condition. Gels were used to remove unsuitable guards whilst preserving the susceptible surface of the original paper. A gelatine-based remoistenable tissue was chosen to mechanically stabilize deteriorated copper-green pigment, and JunFunori used to consolidate flaking pigments. Finally, a slotted folder was created to house each folio, resulting in a flexible system suitable for both consultation and display