Fasting plasma glucose, diagnosis of gestational diabetes and the risk of large for gestational age: a regression discontinuity analysis of routine data.

OBJECTIVE: To estimate the causal effects of fasting plasma glucose (FPG) and diagnosis of gestational diabetes (GDM) on birthweight and the risks of large for gestational age (LGA). DESIGN: Regression discontinuity analysis of routine data. SETTING: Two district general hospitals in West Yorkshire, UK. POPULATION: A cohort of 7062 women with singleton pregnancies who were screened for GDM and gave birth to a baby at ≥24 weeks of gestation in 2017-2019, inclusive. METHODS: The causal effects of FPG and GDM diagnosis were estimated using the two-stage least-squares approach, around the diagnostic threshold of FPG ≥ 5.6 mmol/l recommended by the UK's National Institute for Health and Care Excellent (NICE), controlling for ethnicity, maternal age, parity, height and weight. MAIN OUTCOME MEASURES: Birthweight (standardised for sex and gestational age) and large for gestational age (standardised as birthweight above the 90th centile). RESULTS: For each 1 mmol/l increase in FPG the observed birthweight increased by Z-score = 0.48 standard deviations (95% CI 0.39 to 0.57) and the odds of LGA increased by OR = 2.61 (95% CI 1.86 to 3.66). Conversely, GDM diagnosis reduced the observed birthweight by Z = -0.61 (95% CI -0.94 to -0.29) and lowered the odds of LGA by OR = 0.33 (95% CI 0.15 to 0.74). Similar, but less certain, patterns were observed for caesarean section, shoulder dystocia and perinatal death. CONCLUSIONS: The relationship between FPG and LGA is potent but is dramatically reduced by GDM diagnosis (and all the consequences thereof). Women with mild hyperglycaemia (with an FPG of 5.1-5.5 mmol/l) who fall below the current NICE threshold for GDM diagnosis have the highest risks of adverse outcomes, suggesting a need to reconsider their current care. TWEETABLE ABSTRACT: Regression discontinuity analysis shows that untreated mild hyperglycaemia increases the odds of large for gestational age, but that a diagnosis of gestational #diabetes lowers the odds by three times.

Multidisciplinary team meeting and EUSOMA quality indicators in breast cancer care: A French regional multicenter study.

INTRODUCTION: We evaluate breast cancer (BC) pathway at a regional level including public, private and university institutions. We assessed the quality of multidisciplinary team meetings (MTM) and compliance with a panel of European high-quality indicators (EUSOMA QIs). METHODS: We conducted a retrospective multicenter (n = 20) study in the largest health care region in France. Between January and April 2015, we included all patients discussed at an MTM after a diagnosis of BC (n = 619). We analyzed quality of MTM by assessing the quorum, the reliability of data transcription and the exhaustivity of pre-therapeutic MTM. We then analyzed the compliance with a selected panel of 16 EUSOMA QIs. RESULTS: During MTM discussion, data were more than 95% consistent with medical records for 9/11 items. Pre-operative tumor histology (90.6%) and post-operative resection margins (84.3%) were the least concordant between medical records and MTM. Minimum standards as defined by EUSOMA were reached for 11/16 QIs, but not reached for pathology reports in non-invasive BC (78.2%), proportion of exclusive sentinel lymph node biopsies in patients with clinically negative axilla (85.2%), performing adjuvant chemotherapy (76.6%), and proportion of patients discussed in pre-therapeutic and post-operative MTM (63.5%). CONCLUSIONS: In this multicentric study evaluating the quality of BC care with a representative sample of institutions, compliance with EUSOMA indicators was satisfactory for all type of institutions. However, too few patients were discussed in pre-therapeutic MTM (especially in non-university hospitals 43.7% [39.4-48.1]) versus 88.7% for others [82.2-95.1]) and data transcription was likely responsible for up to 15% of discordance.

Are there variations in adherence to colorectal cancer clinical guidelines depending on treatment place and recommendation novelty? The French EvaCCoR observational study.

BACKGROUND: Studies have shown clinical practices variation between centers in colorectal cancer (CRC) management. After the implementation of national cancer plans, we tested for differences in center and patients' socioeconomic position (SEP)-related variation in CRC guidelines. METHODS: All patients aged 18 years and over, cared for a first CRC in 2010 in Southwest of France. We used mixed effect model to test for center-related heterogeneity (CRH) in recommendation, from the oldest to the more recent: (1) at least 12 lymph nodes analysed for stage II, (2) the prescription of adjuvant chemotherapy stage III and (3) the assessment of CRC molecular phenotype regarding KRAS status for stage IV. Patients' SEP was approached by an ecological social deprivation index. RESULTS: We found: higher adherence for the oldest than for the most recent recommendations; no CRH in recommendation No. 2 but lower adherence in academic centers; a CRH for recommendations No. 1 and 3; no SEP-related differences in clinical practices. CONCLUSION: Results showed that older recommendations have higher adherence but did not support increasing influence of centers characteristics and CRH as recommendations are more recent.

Using predicted 30 day mortality to plan postoperative colorectal surgery care: a cohort study.

BACKGROUND: Preoperative identification of high-risk surgical patients might help to reduce postoperative morbidity and mortality. Using a patient's predicted 30 day mortality to plan postoperative high-dependency unit (HDU) care after elective colorectal surgery might be associated with reduced postoperative morbidity. METHODS: The 30 day postoperative mortality was predicted for 504 elective colorectal surgical patients in a preoperative clinic. The prediction was used to determine postoperative surgical ward or HDU care. Those with a predicted 30 day mortality of 1-3% mortality, and thus deemed at intermediate risk, had either planned HDU care (n=68) or planned ward care (n=139). The main outcome measures were emergency laparotomy and unplanned critical care admission. RESULTS: There were more emergency laparotomies and unplanned critical care admissions in patients with a predicted 30 day mortality of 1-3% who went to an HDU after surgery compared with patients who went to a ward: 0 vs 14 (10%), P=0.0056 and 0 vs 22 (16%), P=0.0002, respectively. CONCLUSIONS: Planned postoperative critical care was associated with a lower rate of complications after elective colorectal surgery.

Preparation of Biocatalytic Microparticles by Interfacial Self-Assembly of Enzyme-Nanoparticle Conjugates Around a Cross-Linkable Core.

Rational design of hierarchical interfacial assembly of reusable biocatalytic microparticles is described in this chapter. Specifically, purified enzymes and functionalized nanoparticles are electrostatically assembled at the interface of cross-linked microparticles which are formed through ring opening metathesis polymerization. The diameters of microparticle assemblies average 10µm, and they show enhanced kinetic efficiency as well as improved stability against heat, pH, and solvent denaturation when compared to stabilities of the corresponding native enzymes.

Symmetry relations in viscoplastic drag laws.

The following note shows that the symmetry of various resistance formulae, often based on Lorentz reciprocity for linearly viscous fluids, applies to a wide class of nonlinear viscoplastic fluids. This follows from Edelen's nonlinear generalization of the Onsager relation for the special case of strongly dissipative rheology, where constitutive equations are derivable from his dissipation potential. For flow domains with strong dissipation in the interior and on a portion of the boundary, this implies strong dissipation on the remaining portion of the boundary, with strongly dissipative traction-velocity response given by a dissipation potential. This leads to a nonlinear generalization of Stokes resistance formulae for a wide class of viscoplastic fluid problems. We consider the application to nonlinear Darcy flow and to the effective slip for viscoplastic flow over textured surfaces.

Ultrastructure of Presumed "Candidatus Rickettsia Andeanae" in Amblyomma maculatum (Acari: Ixodidae).

Amblyomma maculatum Koch, 1844 (also known as the Gulf Coast tick) is found in parts of the Americas, including the central and southern United States. Its primary importance is as the vector of Rickettsia parkeri, a spotted fever group rickettsia that causes an illness similar to, but milder than, Rocky Mountain spotted fever. A second spotted fever group rickettsia, "Candidatus Rickettsia andeanae," was detected in Gulf Coast ticks approximately 10 yr ago. However, the significance of this organism, including pathogenicity, has not yet been well-characterized. Here, we use transmission electron microscopy to describe bacteria within the tissues of A. maculatum ticks that were positive by polymerase chain reaction assay for "Ca. R. andeanae." In ultrathin sections of unfed A. maculatum adult females, we found evidence of bacteria with morphological features consistent with spotted fever group rickettsiae, including small size (≈0.3 by 0.9 µm), a halo zone (electron-lucent layer around the bacterium), and a trilaminar cell wall. In female ticks, bacteria were present in granular salivary glands and ducts, foregut, Malpighian tubules, nerve trunks, and reproductive tissue. These findings demonstrate evidence of "Ca. R. andeanae" in situ and contribute to our understanding of this novel rickettsia in A. maculatum.

Adherence to consensus-based diagnosis and treatment guidelines in adult soft-tissue sarcoma patients: a French prospective population-based study.

BACKGROUND: Soft-tissue sarcomas (STSs) are rare tumors with varied histological presentations. Management and treatment are thus complex, but crucial for patient outcomes. We assess adherence to adult STS management guidelines across two French regions (10% of the French population). We also report standardized incidence. PATIENTS AND METHODS: STS patients diagnosed from 1 November 2006 to 31 December 2007 were identified from pathology reports, medical hospital records, and cancer registries. Guideline adherence was assessed by 23 criteria (validated by Delphi consensus method), and age and sex-standardized incidence rates estimated. Associations between patient, treatment, and institutional factors and adherence with three major composite criteria relating to diagnostic imaging and biopsy as well as multidisciplinary team (MDT) case-review are reported. RESULTS: Two hundred and seventy-four patients were included (57.7% male, mean age 60.8 years). Practices were relatively compliant overall, with over 70% adherence for 10 criteria. Three criteria with perfect Delphi consensus had low adherence: receiving histological diagnosis before surgery, adequacy of histological diagnosis (adherence around 50% for both), and MDT discussion before surgery (adherence <30%). Treatment outside of specialized centers was associated with lower adherence for all three composite criteria, and specific tumor sites and/or features were associated with lower adherence for diagnostic imaging, methods, and MDT meetings. STS standardized incidence rates were 4.09 (European population) and 3.33 (World) /100 000 inhabitants. CONCLUSIONS: Initial STS diagnosis and treatment across all stages (imaging, biopsy, and MDT meetings) need improving, particularly outside specialized centers. Educational interventions to increase surgeon's sarcoma awareness and knowledge and to raise patients' awareness of the importance of seeking expert care are necessary.

Isolation of "Candidatus Rickettsia andeanae" (Rickettsiales: Rickettsiaceae) in embryonic cells of naturally infected Amblyomma maculatum (Ixodida: Ixodidae).

The Gulf Coast tick, Amblyomma maculatum Koch, has become increasingly important in public health for its role as a vector of the recently recognized human pathogen, Rickettsia parkeri. More recently, these ticks were also found to harbor a novel spotted fever group rickettsia, "Candidatus Rickettsia andeanae." First identified in Peru, and subsequently reported in ticks collected in the United States, Chile, and Argentina, "Ca. R. andeanae" remains largely uncharacterized, in part because of the lack of a stable isolate. Although the isolation of "Ca. R. andeanae" was recently described in DH82, Vero, and Drosophila S2 cells, its stability in these cell lines was not shown. To evaluate "Ca. R. andeanae" transmission and pathogenicity in vertebrates, as well as further describe biological characteristics of this candidate species to fulfill criteria for its establishment as a new species, availability of a stable isolate is essential. Here we describe the propagation of "Ca. R. andeanae" by using a primary culture derived from naturally infected A. maculatum embryos. Subsequent passage of the "Ca. R. andeanae" isolate to ISE6 (Ixodes scapularis embryonic) and Vero (African green monkey kidney epithelial) cell lines demonstrated limited propagation of the rickettsiae. Treatment of the infected primary cells with tetracycline resulted in cultures negative for "Ca. R. andeanae" by polymerase chain reaction and microscopy. Establishment of an isolate of "Ca. R. andeanae" will promote further investigation into the significance of this tick-associated rickettsia, including its role in spotted fever and interactions with the sympatric species, R. parkeri in A.

Covalent immobilization of lysozyme on ethylene vinyl alcohol films for nonmigrating antimicrobial packaging applications.

The objective of this study was to develop a new antimicrobial film, in which lysozyme was covalently attached onto two different ethylene vinyl alcohol copolymers (EVOH 29 and EVOH 44). The EVOH surface was modified with UV irradiation treatment to generate carboxylic acid groups, and lysozyme was covalently attached to the functionalized polymer surface. Surface characterization of control and modified films was performed using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and dye assay. The value of protein loading after attachment on the surface was 8.49 µg protein/cm(2) and 5.74 µg protein/cm(2) for EVOH 29 and EVOH 44, respectively, after 10 min UV irradiation and bioconjugation. The efficacy of the EVOH-lysozyme films was assessed using Micrococcus lysodeikticus. The antimicrobial activity of the films was tested against Listeria monocytogenes and was similar to an equivalent amount of free enzyme. The reduction was 1.08 log for EVOH 29-lysozyme, 0.95 log for EVOH 44-lysozyme, and 1.34 log for free lysozyme. This work confirmed the successful use of lysozyme immobilization on the EVOH surface for antimicrobial packaging.

Study of interaction between NO radicals and Martin's spirosilane by means of IR spectroscopy.

The matrix isolation method is used to record the IR spectrum of C18H8O2F12Si in the 4000-500 cm(-1) range. To gain an IR spectrum with a sufficient resolution, this technique was used with neon as the dilution medium at 5 K. The generated species were characterized by in situ fourier transform infrared (FT-IR) spectroscopy. Once the Martin's spirosilane 1 (C18H8O2F12Si) was characterized, its reactivity toward NO was investigated under the same experimental conditions (i.e., using neon as a dilution medium at 5 K). In this case, the use of neon at very low temperature leads to the formation of a chemically inert matrix in which the species are trapped and isolated from one another, thus hindering consecutive reactions. As a consequence, intermediates can be observed. This approach allowed us to characterize the NO adduct, leading to the formation of 1-(NO). Concentration effects as well as annealing experiments were carried out. In addition to this experimental approach, products were identified by using reference spectra. Our results proved that, in the dilute phase, the reaction between 1 and NO radicals leads to the formation of an adduct. This stable species can further react with NO to form a more stable compound: 1-(NO)2. This proves the ability of such species to trap NO.

Positron emission tomography detected thyroid incidentaloma.

We describe the case of a 48-year-old woman who presented with a thyroid lesion incidentally detected on positron emission tomography/computed tomography for a suspicious lung lesion. Subsequent clinical examination and investigations revealed a 3 cm nodule in the left lower pole of the thyroid. Fine needle aspiration was indeterminate for malignancy. A left hemithyroidectomy was performed and histology confirmed a benign thyroid adenoma with an incidental micropapillary carcinoma. The literature regarding the best management for thyroid incidentalomas remains uncertain and, as such, each patient must be managed on an individual basis.

The development of a supraregional network for the management of penile cancer.

INTRODUCTION: Although its incidence is increasing, penile cancer remains a rare disease in the UK. In view of this low volume, the National Institute for Clinical Excellence recommended that treatment is centralised in a limited number of centres arranged as supraregional networks. The aim of this centralisation is to allow the best standardised treatment for the primary tumours and nodal disease, thereby avoiding under or overtreatment. In this paper we review the formation and functioning of our network in the East Midlands. METHODS: Data were collected up to August 2010 from our prospective penile network database since its inception in 2005. These data were analysed to see our workload, patterns of referral and surgeries performed over this time period. RESULTS: The structure and function of the East Midlands network are described. There has been an increase in the number of cases discussed since its formation. There has also been a trend towards more conservative surgery, both of the primary tumour and of nodal management. Between September 2009 and August 2010, 16 glansectomies were performed versus 5 total and 9 partial penectomies. The same period saw 18 dynamic sentinel lymph node biopsies against 7 bilateral and 3 unilateral superficial groin dissections. There was a very high patient satisfaction rate, with patients feeling they had good support and information. CONCLUSIONS: On reviewing the literature it can be clearly seen that supraregional networks have led to a decrease in overtreatment and better recognition of the need to manage lymph node status optimally. Our network has demonstrated the trend toward conservative surgery and sentinel node biopsy. The formation of supraregional networks with a multidisciplinary approach will facilitate high volume centres that will offer optimal surgical therapy and also allow recruitment into studies and new chemotherapeutic regimens. It will also allow better data collection to aid clinical studies that hopefully will also demonstrate better outcomes.

First record of Aedes japonicus japonicus in Mississippi.

In July 2011, 7 late-stage larvae of Aedes japonicus japonicus were collected from a 5-gal bucket located behind a house in Fulton, MS. Three of the larvae were reared to the adult stage, with the remaining retained in 70% ethanol. Fifteen subsequent attempts over the next month to collect specimens by larval dipping in artificial containers at the property and surrounding towns in 3 adjacent counties all failed to produce any additional Ae. j. japonicus.

[Completeness and quality of multidisciplinary team meetings: the example of prostate cancer in the Mid-Pyrenees region]. / Exhaustivité et qualité des réunions de concertation pluridisciplinaire: l'exemple des cancers prostatiques en Midi-Pyrénées.

OBJECTIVES: To determine the completeness of the examination of cancer patient cases in a multidisciplinary team meeting (MDTM), to study the factors that can affect this examination and to assess the quality of the MDTM concerning prostate cancer in Tarn. METHODS: Completeness was estimated by comparing the database of the Tarn cancer registry containing all the inhabitants of this department for whom prostate cancer was diagnosed in 2007 with the list of patients living in Tarn whose cases were discussed during a Midi-Pyrénées MDTM. Determinants of the case discussion in MDTM were studied from data collected in medical records (age, stage at diagnosis, PSA level, Gleason score, treatment). The MDTM quality study (delay in management, whether the case was seen before or after treatment, required elements for MDTM, clinical data, conformity between suggested treatment and guidelines, adequacy between suggested and performed treatments) was based on the MDTM forms retrieved from the DCO and from medical records. RESULTS: Four hundred and fifty-nine patients were re-examined. The pretherapeutic passage rate within three months after diagnosis was 56.2%. The probability of a discussion in MDTM decreased for people over 85 years of age (OR=0.10) compared with the 70-74 year-old people and it increased for the N+M+ (OR=4.23) compared with the T1-T2. Patients for whom radiotherapy was considered were presented more frequently than the others. The MDTM quality was studied based on 220 DCO forms. The patient's physician attended the MDTM in 65% of the cases, 97% of the suggested treatments were consistent with the guidelines and 90% of the performed treatments complied with the suggested treatment. CONCLUSION: The discussion rate in MDTM has not reached the 100% planned by the first "plan cancer" yet, but when a MDTM was carried out, its compliance and adequacy were high. While seniors' cases require interdisciplinarity because of a complicated management, they were less discussed in MDTM.

Multicenter phase II trial of the heat shock protein 90 inhibitor, retaspimycin hydrochloride (IPI-504), in patients with castration-resistant prostate cancer.

OBJECTIVE: To evaluate clinical activity and safety of retaspimycin hydrochloride (IPI-504) in patients with castration-resistant prostate cancer (CRPC). METHODS: A single-arm trial was conducted in 2 cohorts: group 1, chemotherapy naive; group 2, docetaxel-treated. IPI-504 was administered intravenously at 400 mg/m2 on days 1, 4, 8, and 11 of a 21-day cycle. Trial expansion was planned if ≥1 prostate-specific antigen (PSA) or radiographic response was noted per cohort. Pharmacokinetic samples were collected after the first dose; safety was assessed throughout. RESULTS: A total of 19 patients were enrolled (4 in group 1; 15 in group 2), with a median age of 66 years (range 49-78). Group 2 had received a median of 2 previous chemotherapy regimens. All group 2 patients had bone metastases; 66% had measurable soft tissue or visceral metastases. One group 1 patient remained on-trial for 9 cycles; his PSA level declined 48% from baseline. No PSA response was observed in the other patients. Adverse events reported in >25% of the study population included nausea (47%), diarrhea (42%), fatigue (32%), anorexia (26%), and arthralgia (26%). Two patients in group 2 died on-trial, involving study drug-related events of hepatic failure and ketoacidosis, respectively. CONCLUSION: Heat shock protein 90 inhibition with IPI-504 administered as a single agent had a minimal effect on the PSA level or tumor burden and was associated with unacceptable toxicity in several patients. Therefore, additional evaluation in CRPC patients is not warranted. IPI-504 is being investigated at less-intensive doses and schedules in other tumor types.

Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear.

Murine models are ideal for studying cochlear gene transfer, as many hearing loss-related mutations have been discovered and mapped within the mouse genome. However, because of the small size and delicate nature, the membranous labyrinth of the mouse is a challenging target for the delivery of viral vectors. To minimize injection trauma, we developed a procedure for the controlled release of adeno-associated viruses (AAVs) into the scala media of adult mice. This procedure poses minimal risk of injury to structures of the cochlea and middle ear, and allows for near-complete preservation of low and middle frequency hearing. In this study, transduction efficiency and cellular specificity of AAV vectors (serotypes 1, 2, 5, 6 and 8) were investigated in normal and drug-deafened ears. Using the cytomegalovirus promoter to drive gene expression, a variety of cell types were transduced successfully, including sensory hair cells and supporting cells, as well as cells in the auditory nerve and spiral ligament. Among all five serotypes, inner hair cells were the most effectively transduced cochlear cell type. All five serotypes of AAV vectors transduced cells of the auditory nerve, though serotype 8 was the most efficient vector for transduction. Our findings indicate that efficient AAV inoculation (via the scala media) can be performed in adult mouse ears, with hearing preservation a realistic goal. The procedure we describe may also have applications for intra-endolymphatic drug delivery in many mouse models of human deafness.

SDetection of vector-borne agents in lone star ticks, Amblyomma americanum (Acari: Ixodidae), from Mississippi.

In this study, we evaluated Amblyomma americanum (lone star tick) in Mississippi for the presence of Ehrlichia chaffeensis, causative agent of human monocytic ehrlichiosis; Ehrlichia ewingii, causative agent of human and canine granulocytic ehrlichiosis; Borrelia lonestari, putative agent of southern tick-associated rash illness; Francisella tularensis, the agent of tularemia; and Rickettsia spp., particularly R. amblyommii, a suspected pathogen. We collected adult A. americanum from four regions of Mississippi: Northeast, Northwest, Southeast, and East. Of the ticks collected, 192 were dissected and DNA was extracted for nested polymerase chain reaction (PCR) assays to detect the above bacteria. In all, 3% of tick extracts had evidence of Borrelia sp., 4% for E. chaffeensis, 6% for E. ewingii, and 44% for a Rickettsia species. As determined by sequencing, most Rickettsia spp. were R. amblyommii. In addition, extracts from 42 pools (total of 950) of larval A. americanum collected in Southwest Mississippi were tested for the presence of E. chaffeensis and Rickettsia species. Of these extracts from pools, nine of 37 (24%) were PCR positive for a Rickettsia sp., most often, R. amblyommii; none had evidence of E. chaffeensis, supporting the ability of lone star ticks to transovarially transmit R. amblyommii, but not E. chaffeensis. This study demonstrates E. chaffeensis, E. ewingii, "B. lonestari", and R. amblyommii in A. americanum by PCR for the first time in Mississippi. Understanding the prevalence and epidemiology of these agents in Mississippi should increase awareness of tick-borne disease in the medical community.

Determination of some heavy metal concentrations in razor clam (Solen brevis) from Tanjung Lumpur coastal waters, Pahang, Malaysia.

An effort to analyze selected heavy metal accumulation by the razor clam (Solen brevis) from Tanjung Lumpur was conducted on January to April 2010. A total of fifty individuals of Razor clam Solen brevis were sampled and metals such as Iron (Fe), Zinc (Zn), Copper (Cu), Manganese (Mn), Lead (Pb) and Cadmium (Cd) Concentrations were determined using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Among the metals Fe occurred in elevated concentration in the soft tissue of razor clam followed by Zn. Cd was found to be in least concentration in the sample. Mean concentration of Fe, Zn, Mn, Cu, Cd and Pb in the soft tissue were 415.2 +/- 56.52, 87.74 +/- 11.85, 18.71 +/- 2.10, 8.64 +/- 1.75, 0.67 +/- 0.29 and 1.61 +/- 0.45 microg g(-1) dw, respectively indicating that the bioaccumulation of essential metals in the soft tissue was greater than the non essential heavy metals. Metal accumulation in the soft tissue of razor clam followed Fe > Zn > Mn > Cu > Pb > Cd order in present study. The observed concentration of acute toxicity of metals in Solen brevis (Family: Solenidae) from Tanjung Lumpur Coastal waters was lower than the permissible limit recommended by National and international standards proved that this species could be utilized for human consumption.