bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multihelix rotating shield brachytherapy for cervical cancer
Authors: Dadkhah Hossein , Kim Yusung , Wu Xiaodong , Flynn Ryan T. 
Published: October 2015

Purpose:To present a novel brachytherapy technique, called multihelix rotating shield brachytherapy (H‐RSBT), for the precise angular and linear positioning of a partial shield in a curved applicator. H‐RSBT mechanically enables the dose delivery using only linear translational motion of the radiation source/shield combination. The previously proposed approach of serial rotating shield brachytherapy (S‐RSBT), in which the partial shield is rotated to several angular positions at each source dwell position [W. Yang et al., “Rotating‐shield brachytherapy for cervical cancer,” Phys. Med. Biol. 58, 3931–3941 (2013)], is mechanically challenging to implement in a curved applicator, and H‐RSBT is proposed as a feasible solution.Methods:A Henschke‐type applicator, designed for an electronic brachytherapy source (Xoft Axxent™) and a 0.5 mm thick tungsten partial shield with 180° or 45° azimuthal emission angles and 116° asymmetric zenith angle, is proposed. The interior wall of the applicator contains six evenly spaced helical keyways that rigidly define the emission direction of the partial radiation shield as a function of depth in the applicator. The shield contains three uniformly distributed protruding keys on its exterior wall and is attached to the source such that it rotates freely, thus longitudinal translational motion of the source is transferred to rotational motion of the shield. S‐RSBT and H‐RSBT treatment plans with 180° and 45° azimuthal emission angles were generated for five cervical cancer patients with a diverse range of high‐risk target volume (HR‐CTV) shapes and applicator positions. For each patient, the total number of emission angles was held nearly constant for S‐RSBT and H‐RSBT by using dwell positions separated by 5 and 1.7 mm, respectively, and emission directions separated by 22.5° and 60°, respectively. Treatment delivery time and tumor coverage (D90 of HR‐CTV) were the two metrics used as the basis for evaluation and comparison. For all the generated treatment plans, the D90 of the HR‐CTV in units of equivalent dose in 2 Gy fractions (EQD2) was escalated until the D2cc (minimum dose to hottest 2 cm3) tolerance of either the bladder (90 Gy3), rectum (75 Gy3), or sigmoid colon (75 Gy3) was reached.Results:Treatment time changed for H‐RSBT versus S‐RSBT by −7.62% to 1.17% with an average change of −2.8%, thus H‐RSBT treatments times tended to be shorter than for S‐RSBT. The HR‐CTV D90 also changed by −2.7% to 2.38% with an average of −0.65%.Conclusions:H‐RSBT is a mechanically feasible delivery technique for use in the curved applicators needed for cervical cancer brachytherapy. S‐RSBT and H‐RSBT were clinically equivalent for all patients considered, with the H‐RSBT technique tending to require less time for delivery.
Improved quality of intrafraction kilovoltage images by triggered readout of unexposed frames
Authors: Poulsen Per Rugaard , Jonassen Johnny , Schmidt Mai Lykkegaard , Jensen Carsten 
Published: October 2015

Purpose:The gantry‐mounted kilovoltage (kV) imager of modern linear accelerators can be used for real‐time tumor localization during radiation treatment delivery. However, the kV image quality often suffers from cross‐scatter from the megavoltage (MV) treatment beam. This study investigates readout of unexposed kV frames as a means to improve the kV image quality in a series of experiments and a theoretical model of the observed image quality improvements.Methods:A series of fluoroscopic images were acquired of a solid water phantom with an embedded gold marker and an air cavity with and without simultaneous radiation of the phantom with a 6 MV beam delivered perpendicular to the kV beam with 300 and 600 monitor units per minute (MU/min). An in‐house built device triggered readout of zero, one, or multiple unexposed frames between the kV exposures. The unexposed frames contained part of the MV scatter, consequently reducing the amount of MV scatter accumulated in the exposed frames. The image quality with and without unexposed frame readout was quantified as the contrast‐to‐noise ratio (CNR) of the gold marker and air cavity for a range of imaging frequencies from 1 to 15 Hz. To gain more insight into the observed CNR changes, the image lag of the kV imager was measured and used as input in a simple model that describes the CNR with unexposed frame readout in terms of the contrast, kV noise, and MV noise measured without readout of unexposed frames.Results:Without readout of unexposed kV frames, the quality of intratreatment kV images decreased dramatically with reduced kV frequencies due to MV scatter. The gold marker was only visible for imaging frequencies ≥3 Hz at 300 MU/min and ≥5 Hz for 600 MU/min. Visibility of the air cavity required even higher imaging frequencies. Readout of multiple unexposed frames ensured visibility of both structures at all imaging frequencies and a CNR that was independent of the kV frame rate. The image lag was 12.2%, 2.2%, and 0.9% in the first, second, and third frame after an exposure. The CNR model predicted the CNR with triggered image readout with a mean absolute error of 2.0% for the gold marker.Conclusions:A device that triggers readout of unexposed frames during kV fluoroscopy was built and shown to greatly improve the quality of intratreatment kV images. A simple theoretical model successfully described the CNR improvements with the device.
Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit
Authors: Abdul-Aziz Mohd H. , Abd Rahman Azrin N. , Mat-Nor Mohd-Basri , Sulaiman Helmi , Wallis Steven C. , Lipman Jeffrey , Roberts Jason A. , Staatz Christine E. 
Published: October 2015

ABSTRACT

Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL
CR
), such that a 30-ml/min increase in the estimated CL
CR
would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL
CR
of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL
CR
of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.
Molecular Characterization of Carbapenem-Nonsusceptible Enterobacterial Isolates Collected during a Prospective Interregional Survey in France and Susceptibility to the Novel Ceftazidime-Avibactam and Aztreonam-Avibactam Combinations
Authors: Dupont Hervé , Gaillot Olivier , Goetgheluck Anne-Sophie , Plassart Claire , Emond Jean-Philippe , Lecuru Marion , Gaillard Nicolas , Derdouri Sarah , Lemaire Baptiste , Girard de Courtilles Marion , Cattoir Vincent , Mammeri Hedi 
Published: October 2015

ABSTRACT

An interregional surveillance program was conducted in the northwestern part of France to determine the prevalence of carbapenem-nonsusceptible
Enterobacteriaceae
(CNSE) isolates and their susceptibility to ceftazidime-avibactam and aztreonam-avibactam combinations. Nonduplicate CNSE clinical isolates were prospectively collected from six hospitals between June 2012 and November 2013. MICs of ceftazidime and aztreonam, alone or combined with a fixed concentration of avibactam (4 μg/ml), and those of carbapenems (comparator agents) were determined. MICs of ertapenem in combination with phenylalanine arginine-naphthylamide dihydrochloride (PAβN) were also determined to assess active efflux. Genes encoding carbapenemases, plasmid-mediated AmpC enzymes, extended-spectrum β-lactamases (ESBLs), and major outer membrane proteins (OMPs) were amplified and sequenced. OMPs were also extracted for SDS-PAGE analysis. Among the 139 CNSE isolates, mainly
Enterobacter
spp. and
Klebsiella pneumoniae
, 123 (88.4%) were ertapenem nonsusceptible, 12 (8.6%) exhibited reduced susceptibility to all carbapenems, and 4
Proteeae
isolates (2.9%) were resistant to imipenem. Carbapenemase production was detected in only two isolates (producing OXA-48 and IMI-3). In contrast, OMP deficiency, in association with AmpCs and/or ESBLs (mainly CTX-M-9, SHV-12, and CTX-M-15), was largely identified among CNSE isolates. The ceftazidime-avibactam and aztreonam-avibactam combinations exhibited potent activity against CNSE isolates (MIC
50
/MIC
90
, 1/1 μg/ml and 0.5/0.5 μg/ml, respectively) compared to that of ceftazidime and aztreonam alone (MIC
50
/MIC
90
, 512/512 μg/ml and 128/512 μg/ml, respectively). This study reveals the
in vitro
activity of ceftazidime-avibactam and aztreonam-avibactam combinations against a large collection of porin-deficient enterobacterial isolates that are representative of the CNSE recovered in the northern part of France.
Risk Factors and Outcomes for Bloodstream Infections Secondary to Clostridium difficile Infection
Authors: Falcone Marco , Russo Alessandro , Iraci Federica , Carfagna Paolo , Goldoni Paola , Vullo Vincenzo , Venditti Mario 
Published: October 2015

ABSTRACT

We determined the incidence, risk factors, and outcomes of bloodstream infections (BSI) subsequent to
Clostridium difficile
infection (CDI). We performed a retrospective study of all patients with definite diagnosis of CDI admitted from January 2014 to December 2014 in two large hospitals in Rome. Two groups of patients were analyzed: those with CDI and subsequent BSI (CDI/BSI
+
) and those with CDI and no evidence of primary BSI (CDI/BSI
−
). Data about clinical features, microbiology, treatments, and mortality were obtained. Overall, 393 cases of CDI were included in the final analysis: 72 developed a primary nosocomial BSI, while 321 had CDI without microbiological and clinical evidence of BSI. Etiologic agents of BSI were
Candida
species (47.3%),
Enterobacteriaceae
(19.4%), enterococci (13.9%), and mixed infections (19.4%). In multivariate analysis, ribotype 027 status (odds ratio [OR], 6.5), CDI recurrence (OR, 5.5), severe CDI infection (OR, 8.3), and oral vancomycin at >500 mg/day (OR, 3.1) were recognized as factors independently associated with the development of nosocomial BSI. Thirty-day mortality from CDI diagnosis was higher for patients of the CDI/BSI
+
group than for the controls (38.9 versus 13.1%;
P
< 0.001). Among patients of the CDI/BSI
+
group, mortality attributable to primary BSI was as high as 57%. Our findings suggest that severe CDI is complicated by the development of nosocomial BSI.
Candida
species and enteric bacteria appear to be the leading causative pathogens and are associated with poor outcomes.
Surface Polysaccharide Mutants Reveal that Absence of O Antigen Reduces Biofilm Formation of Actinobacillus pleuropneumoniae
Authors: Hathroubi S. , Hancock M. A. , Bossé J. T. , Langford P. R. , Tremblay Y. D. N. , Labrie J. , Jacques M. 
Published: October 2015

ABSTRACT

Actinobacillus pleuropneumoniae
is a Gram-negative bacterium belonging to the
Pasteurellaceae
family and the causative agent of porcine pleuropneumonia, a highly contagious lung disease causing important economic losses. Surface polysaccharides, including lipopolysaccharides (LPS) and capsular polysaccharides (CPS), are implicated in the adhesion and virulence of
A. pleuropneumoniae
, but their role in biofilm formation is still unclear. In this study, we investigated the requirement for these surface polysaccharides in biofilm formation by
A. pleuropneumoniae
serotype 1. Well-characterized mutants were used: an O-antigen LPS mutant, a truncated core LPS mutant with an intact O antigen, a capsule mutant, and a poly-
N
-acetylglucosamine (PGA) mutant. We compared the amount of biofilm produced by the parental strain and the isogenic mutants using static and dynamic systems. Compared to the findings for the biofilm of the parental or other strains, the biofilm of the O antigen and the PGA mutants was dramatically reduced, and it had less cell-associated PGA. Real-time PCR analyses revealed a significant reduction in the level of
pgaA
,
cpxR
, and
cpxA
mRNA in the biofilm cells of the O-antigen mutant compared to that in the biofilm cells of the parental strain. Specific binding between PGA and LPS was consistently detected by surface plasmon resonance, but the lack of O antigen did not abolish these interactions. In conclusion, the absence of the O antigen reduces the ability of
A. pleuropneumoniae
to form a biofilm, and this is associated with the reduced expression and production of PGA.
Morphology-Independent Virulence of Candida Species during Polymicrobial Intra-abdominal Infections with Staphylococcus aureus
Authors: Nash Evelyn E. , Peters Brian M. , Fidel Paul L. , Noverr Mairi C. 
Published: October 2015

ABSTRACTIntra-abdominal polymicrobial infections cause significant morbidity and mortality. An experimental mouse model ofCandida albicans-Staphylococcus aureusintra-abdominal infection (IAI) results in 100% mortality by 48 to 72 h postinoculation, while monomicrobial infections are avirulent. Mortality is associated with robust local and systemic inflammation without a requirement forC. albicansmorphogenesis. However, the contribution of virulence factors coregulated during the yeast-to-hypha transition is unknown. This also raised the question of whether otherCandidaspecies that are unable to form hyphae are as virulent asC. albicansduring polymicrobial IAI. Therefore, the purpose of this study was to evaluate the ability of non-albicans Candida(NAC) species with various morphologies andC. albicanstranscription factor mutants (efg1/efg1andcph1/cph1) to induce synergistic mortality and the accompanying inflammation. Results showed thatS. aureuscoinoculated withC. kruseiorC. tropicaliswas highly lethal, similar toC. albicans, whileS. aureus-C. dubliniensis,S. aureus-C. parapsilosis, andS. aureus-C. glabratacoinoculations resulted in little to no mortality. Local and systemic interleukin-6 (IL-6) and prostaglandin E2(PGE2) levels were significantly elevated during symptomatic and/or lethal coinfections, and hypothermia strongly correlated with mortality. Coinoculation withC. albicansstrains deficient in the transcription factor Efg1 but not Cph1 reversed the lethal outcome. These results support previous findings and demonstrate that selectCandidaspecies, without reference to any morphological requirement, induce synergistic mortality, with IL-6 and PGE2acting as key inflammatory factors. Mechanistically, signaling pathways controlled by Efg1 are critical for the ability ofC. albicansto induce mortality from an intra-abdominal polymicrobial infection.
Global and Targeted Lipid Analysis of
Gemmata obscuriglobus
Reveals the Presence of Lipopolysaccharide, a Signature of the Classical Gram-Negative Outer Membrane
Authors: Mahat Rajendra , Seebart Corrine , Basile Franco , Ward Naomi L. 
Published: October 2015

ABSTRACT

Planctomycete bacteria possess many unusual cellular properties, contributing to a cell plan long considered to be unique among the bacteria. However, data from recent studies are more consistent with a modified Gram-negative cell plan. A key feature of the Gram-negative plan is the presence of an outer membrane (OM), for which lipopolysaccharide (LPS) is a signature molecule. Despite genomic evidence for an OM in planctomycetes, no biochemical verification has been reported. We attempted to detect and characterize LPS in the planctomycete
Gemmata obscuriglobus
. We obtained direct evidence for LPS and lipid A using electrophoresis and differential staining. Gas chromatography-mass spectrometry (GC-MS) compositional analysis of LPS extracts identified eight different 3-hydroxy fatty acids (3-HOFAs), 2-keto 3-deoxy-
d
-manno-octulosonic acid (Kdo), glucosamine, and hexose and heptose sugars, a chemical profile unique to Gram-negative LPS. Combined with molecular/structural information collected from matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) MS analysis of putative intact lipid A, these data led us to propose a heterogeneous hexa-acylated lipid A structure (multiple-lipid A species). We also confirmed previous reports of
G. obscuriglobus
whole-cell fatty acid (FA) and sterol compositions and detected a novel polyunsaturated FA (PUFA). Our confirmation of LPS, and by implication an OM, in
G. obscuriglobus
raises the possibility that other planctomycetes possess an OM. The pursuit of this question, together with studies of the structural connections between planctomycete LPS and peptidoglycans, will shed more light on what appears to be a planctomycete variation on the Gram-negative cell plan.

IMPORTANCE
Bacterial species are classified as Gram positive or negative based on their cell envelope structure. For 25 years, the envelope of planctomycete bacteria has been considered a unique exception, as it lacks peptidoglycan and an outer membrane (OM). However, the very recent detection of peptidoglycan in planctomycete species has provided evidence for a more conventional cell wall and raised questions about other elements of the cell envelope. Here, we report direct evidence of lipopolysaccharide in the planctomycete
G. obscuriglobus
, suggesting the presence of an OM and supporting the proposal that the planctomycete cell envelope is an extension of the canonical Gram-negative plan. This interpretation features a convoluted cytoplasmic membrane and expanded periplasmic space, the functions of which provide an intriguing avenue for future investigation.
Unplanned admissions and the organisational management of heart failure: a multicentre ethnographic, qualitative study
Authors: Simmonds Rosemary , Glogowska Margaret , McLachlan Sarah , Cramer Helen , Sanders Tom , Johnson Rachel , Kadam Umesh , Lasserson Daniel , Purdy Sarah 
Published: October 2015

ObjectivesHeart failure is a common cause of unplanned hospital admissions but there is little evidence on why, despite evidence-based interventions, admissions occur. This study aimed to identify critical points on patient pathways where risk of admission is increased and identify barriers to the implementation of evidence-based interventions.DesignMulticentre, longitudinal, patient-led ethnography.SettingNational Health Service settings across primary, community and secondary care in three geographical locations in England, UK.Participants31 patients with severe or difficult to manage heart failure followed for up to 11 months; 9 carers; 55 healthcare professionals.ResultsFragmentation of healthcare, inequitable provision of services and poor continuity of care presented barriers to interventions for heart failure. Critical points where a reduction in the risk of current or future admission occurred throughout the pathway. At the beginning some patients did not receive a formal clinical diagnosis, in addition patients lacked information about heart failure, self-care and knowing when to seek help. Some clinicians lacked knowledge about diagnosis and management. Misdiagnoses of symptoms and discontinuity of care resulted in unplanned admissions. Approaching end of life, patients were admitted to hospital when other options including palliative care could have been appropriate.ConclusionsFindings illustrate the complexity involved in caring for people with heart failure. Fragmented healthcare and discontinuity of care added complexity and increased the likelihood of suboptimal management and unplanned admissions. Diagnosis and disclosure is a vital first step for the patient in a journey of acceptance and learning to self-care/monitor. The need for clinician education about heart failure and specialist services was acknowledged. Patient education should be seen as an ongoing ‘conversation’ with trusted clinicians and end-of-life planning should be broached within this context.
Elevated expression of ASCL2 is an independent prognostic indicator in lung squamous cell carcinoma
Authors: Hu Xu-gang , Chen Lu , Wang Qing-liang , Zhao Xi-long , Tan Juan , Cui You-hong , Liu Xin-dong , Zhang Xia , Bian Xiu-wu 
Published: October 2015

AimsASCL2, a basic helix-loop-helix (bHLH) transcription factor, is putatively involved in tumour progression. This study aimed to evaluate ASCL2 expression level in non-small-cell carcinoma (NSCLC) and assess its prognostic value for patients.MethodsASCL2 protein expression was detected by immunohistochemistry (IHC cohort) in 79 cases of squamous cell carcinoma (SCC) and 67 cases of adenocarcinoma (AC). Kaplan–Meier analysis and Cox regression analysis were performed to evaluate the prognostic significance of ASCL2. The same analyses were conducted in a cohort (n=790) from The Cancer Genome Atlas database (TCGA) to validate the expression pattern and prognostic value of ASCL2.ResultsASCL2 expression levels were significantly increased in SCC compared with normal lung tissue (p<0.001) and AC (p=0.008). High ASCL2 expression was associated with advanced tumour-node-metastasis (TNM) stage (p=0.023) and worse differentiation status (p=0.001) in SCC, but a positive correlation between ASCL2 expression level and advanced TNM stage (p=0.016) was observed in AC. Kaplan–Meier analysis showed that ASCL2 was prognostic in SCC (p=0.004) but not in AC (p=0.183). Multivariable Cox regression analysis indicated that elevated expression of ASCL2 was an independent prognostic factor (HR 2.764; p=0.030) in SCC patients. The expression pattern and prognostic significance of ASCL2 in SCC and AC were validated using the TCGA cohort.ConclusionsElevated expression of ASCL2 may identify an aggressive subgroup in SCC and serve as an independent prognostic indicator in these patients.