Internal accounting practices at Whitbread & Company c.1890-1925

This paper examines internal accounting practices at Whitbread & Company from c. 1890 to 1925. At this time, there was an increasing interest in cost accounting, but there is little detailed extant research on general internal accounting practices of firms. The brewing sector, we suggest, is a potentially fruitful realm to further our knowledge of this time. Drawing on the Whitbread brewery archival records, we chart the internal accounting practices of the company. Our findings reveal a stable set of accounting practices, focused mainly on bookkeeping, although the firm’s auditor produced some reports which may have been useful for management decision-making. We argue these practices were highly institutionalised, and seemingly resistant to external forces present in the company’s environment

Agreement among Health Care Professionals in Diagnosing Case Vignette-Based Surgical Site Infections

OBJECTIVE: To assess agreement in diagnosing surgical site infection (SSI) among healthcare professionals involved in SSI surveillance. METHODS: Case-vignette study done in 2009 in 140 healthcare professionals from seven specialties (20 in each specialty, Anesthesiologists, Surgeons, Public health specialists, Infection control physicians, Infection control nurses, Infectious diseases specialists, Microbiologists) in 29 University and 36 non-University hospitals in France. We developed 40 case-vignettes based on cardiac and gastrointestinal surgery patients with suspected SSI. Each participant scored six randomly assigned case-vignettes before and after reading the SSI definition on an online secure relational database. The intraclass correlation coefficient (ICC) was used to assess agreement regarding SSI diagnosis on a seven-point Likert scale and the kappa coefficient to assess agreement for superficial or deep SSI on a three-point scale. RESULTS: Based on a consensus, SSI was present in 21 of 40 vignettes (52.5%). Intraspecialty agreement for SSI diagnosis ranged across specialties from 0.15 (95% confidence interval, 0.00-0.59) (anesthesiologists and infection control nurses) to 0.73 (0.32-0.90) (infectious diseases specialists). Reading the SSI definition improved agreement in the specialties with poor initial agreement. Intraspecialty agreement for superficial or deep SSI ranged from 0.10 (-0.19-0.38) to 0.54 (0.25-0.83) (surgeons) and increased after reading the SSI definition only among the infection control nurses from 0.10 (-0.19-0.38) to 0.41 (-0.09-0.72). Interspecialty agreement for SSI diagnosis was 0.36 (0.22-0.54) and increased to 0.47 (0.31-0.64) after reading the SSI definition. CONCLUSION: Among healthcare professionals evaluating case-vignettes for possible surgical site infection, there was large disagreement in diagnosis that varied both between and within specialties

Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification

INTRODUCTION: Amyloid beta (Aβ) oligomers are one of the most toxic structural forms of the Aβ protein and are hypothesized to cause synaptotoxicity and memory failure as they build up in Alzheimer's disease (AD) patients' brain tissue. We previously demonstrated that antagonists of the sigma-2 receptor complex effectively block Aβ oligomer toxicity. CT1812 is an orally bioavailable, brain penetrant small molecule antagonist of the sigma-2 receptor complex that appears safe and well tolerated in healthy elderly volunteers. We tested CT1812's effect on Aβ oligomer pathobiology in preclinical AD models and evaluated CT1812's impact on cerebrospinal fluid (CSF) protein biomarkers in mild to moderate AD patients in a clinical trial (ClinicalTrials.gov NCT02907567). METHODS: Experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer binding to synapses in vitro, to human AD patient post mortem brain tissue ex vivo, and in living APPSwe /PS1dE9 transgenic mice in vivo. Additional experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer-induced deficits in membrane trafficking rate, synapse number, and protein expression in mature hippocampal/cortical neurons in vitro. The impact of CT1812 on cognitive function was measured in transgenic Thy1 huAPPSwe/Lnd+ and wild-type littermates. A multicenter, double-blind, placebo-controlled parallel group trial was performed to evaluate the safety, tolerability, and impact on protein biomarker expression of CT1812 or placebo given once daily for 28 days to AD patients (Mini-Mental State Examination 18-26). CSF protein expression was measured by liquid chromatography with tandem mass spectrometry or enzyme-linked immunosorbent assay in samples drawn prior to dosing (Day 0) and at end of dosing (Day 28) and compared within each patient and between pooled treated versus placebo-treated dosing groups. RESULTS: CT1812 significantly and dose-dependently displaced Aβ oligomers bound to synaptic receptors in three independent preclinical models of AD, facilitated oligomer clearance into the CSF, increased synaptic number and protein expression in neurons, and improved cognitive performance in transgenic mice. CT1812 significantly increased CSF concentrations of Aβ oligomers in AD patient CSF, reduced concentrations of synaptic proteins and phosphorylated tau fragments, and reversed expression of many AD-related proteins dysregulated in CSF. DISCUSSION: These preclinical studies demonstrate the novel disease-modifying mechanism of action of CT1812 against AD and Aβ oligomers. The clinical results are consistent with preclinical data and provide evidence of target engagement and impact on fundamental disease-related signaling pathways in AD patients, supporting further development of CT1812

The relationship between the symptoms of female gonococcal infections and serum progesterone level and the genotypes of Neisseria gonorrhoeae multi-antigen sequence type (NG-MAST) in Wuhan, China

The objective of this investigation was to study the relationship between the symptoms of female gonococcal infections and serum progesterone level and the genotypes of Neisseria gonorrhoeae multi-antigen sequence type (NG-MAST) in Wuhan, China. Eighty-one strains of N. gonorrhoeae were harvested from the vaginal discharge of 975 adult females in Wuhan and were genotyped by using NG-MAST. Serum progesterone (P) and estradiol (E2) levels were measured by radio immunoassay (RIA) in 39 gonorrhea-infected patients with slight symptoms (asymptomatic group) and 42 patients with conspicuous symptoms (symptomatic group). The average levels of serum progesterone in the asymptomatic group were significantly higher than in the symptomatic group (p < 0.05), while no significant difference was found in serum estradiol between the two groups. Of 81 wild-type isolates, 50 NG-MAST sequence types were associated with female infections in Wuhan, and N. gonorrhoeae ST2951, ST735, and ST436 were principally found in asymptomatic patients. ST809 and ST369, however, were mainly detected in asymptomatic female subjects. Gonococcal genetic island (GGI)-positive and GGI-negative strains were found in both the asymptomatic group and the symptomatic group. In females with gonococcal infection, high serum progesterone level is associated with the absence of symptoms, but no association was revealed between genotypes and the presence of symptoms. The GGI bears no relation to the absence of symptoms in the patients

Evaluation of glyceraldehyde-3-phosphate, prolylpeptidyl isomerase A, and a set of stably expressed genes as reference mRNAs in urate crystal inflammation

ABSTRACT

Substantial Alterations of the Cutaneous Bacterial Biota in Psoriatic Lesions

For psoriasis, an idiopathic inflammatory disorder of the skin, the microbial biota has not been defined using cultivation-independent methods. We used broad-range 16S rDNA PCR for archaea and bacteria to examine the microbiota of normal and psoriatic skin. From 6 patients, 19 cutaneous samples (13 from diseased skin and 6 from normal skin) were obtained. Extracted DNA was subjected to the broad range PCR, and 1,925 cloned products were compared with 2,038 products previously reported from healthy persons. Using 98% sequence identity as a species boundary, 1,841 (95.6%) clones were similar to known bacterial 16S rDNA, representing 6 phyla, 86 genera, or 189 species-level operational taxonomic unit (SLOTU); 84 (4.4%) clones with <98% identity probably represented novel species. The most abundant and diverse phylum populating the psoriatic lesions was Firmicutes (46.2%), significantly (P<0.001) overrepresented, compared to the samples from uninvolved skin of the patients (39.0%) and healthy persons (24.4%). In contrast, Actinobacteria, the most prevalent and diverse phylum in normal skin samples from both healthy persons (47.6%) and the patients (47.8%), was significantly (P<0.01) underrepresented in the psoriatic lesion samples (37.3%). Representation of Propionibacterium species were lower in the psoriatic lesions (2.9±5.5%) than from normal persons (21.1±18.2%; P<0.001), whereas normal skin from the psoriatic patients showed intermediate levels (12.3±21.6%). We conclude that psoriasis is associated with substantial alteration in the composition and representation of the cutaneous bacterial biota

Field Longevity of a Fluorescent Protein Marker in an Engineered Strain of the Pink Bollworm, Pectinophora gossypiella (Saunders)

The cotton pest, pink bollworm (Pectinophora gossypiella (Saunders)), is a significant pest in most cotton-growing areas around the world. In southwestern USA and northern Mexico, pink bollworm is the target of the sterile insect technique (SIT), which relies on the mass-release of sterile pink bollworm adults to over-flood the wild population and thereby reduce it over time. Sterile moths reared for release are currently marked with a dye provided in their larval diet. There are concerns, however, that this marker fails from time to time, leading to sterile moths being misidentified in monitoring traps as wild moths. This can lead to expensive reactionary releases of sterile moths. We have developed a genetically marked strain that is engineered to express a fluorescent protein, DsRed2, which is easily screened under a specialised microscope. In order to test this marker under field conditions, we placed wild-type and genetically marked moths on traps and placed them in field cages. The moths were then screened, in a double-blind fashion, for DsRed2 fluorescence at regular intervals to determine marker reliability over time. The marker was shown to be robust in very high temperatures and generally proved reliable for a week or longer. More importantly, genotyping of moths on traps by PCR screening of the moths was 100% correct. Our findings indicate that this strain - and fluorescent protein markers in general - could make a valuable contribution to SIT