bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Effect of Screw Preload on the Stress Distribution of Mandibles During Segmental Defect Treatment Using an Additively Manufactured Hardware
Authors: Amerinatanzi Amirhesam , Shayesteh Moghaddam Narges , Jahadakbar Ahmadreza , Dean David , Elahinia Mohammad
Published: September 2016

The most common method for mandibular reconstructive surgery is the use of a Ti-6Al-4V fixation device and a fibular double barrel graft. This highly stiff fixation hardware (E = 112 GPa) often shields the bone graft (E = 20 GPa) from carrying the load, which may result in bone resorption. Highly stiff Ti-6Al-4V fixation hardware is also likely to concentrate stress in the fixation plate or at screw threads, possibly leading to hardware cracking or screw pull-out. As a solution for that, we have proposed and studied the effect of using a low stiffness, porous NiTi fixation device [1–4]. Although the stress in the fixation device is increased, using such low stiffness fixation hardware, is preferable to have an even higher stress on the graft in order to minimize the risk of resorption or hardware failure. We assume that preloading screws allows them to better engage the fixation hardware with the plate and the surrounding bone and causes an increased von Mises stress. The fixation device can be patient-specific and additively manufactured, such that the shape would match the outer surface of the cortical bone.

In this study, we modeled a healthy cadaver mandible via CT-derived 3D surface data. The mandible was virtually resected in the molar region (M1−3). The model simulated the result of reconstructive surgery under the highest chewing loading regime (i.e., 526 N on first right molar tooth [5, 6]) where reconstruction was done with either Ti-6Al-4V fixation hardware or patient specific, stiffness-matched, porous NiTi fixation hardware. The calibration of the material properties for this simulation was done using experimentally obtained data (DSC and compression tests) of Ni-rich NiTi bulk samples. The analyzed term in the finite element analysis was stress distribution in the cortical and cancellous bone. Porous NiTi fixation devices were also produced using Selective Laser Melting (SLM) using the geometry of the aforementioned cadaver mandible.

In this paper we have studied the effect of additional torque or preload on the performance of the fixation plates. The finite element analysis demonstrated that applying a preload to the screws increased the stress on the bone. Under similar levels of applied preload, the porous NiTi fixation device showed an increased level of von Mises stress in the bone, particularly in the graft. Additionally, the analysis indicated the higher level of stress on the bone surrounding the screws for the case of using NiTi, which could contribute to increasing screw stability. The fabricated patient-specific fixation hardware not only matched the shape of cortical bone but also contained the level of porosity that defines the appropriate modulus of elasticity.
Fabrication of Right Triangular Prism Retroreflectors Through Ultraprecise Single Point Inverted Cutting
Authors: Hamilton Benjamin W. , Hussein Sama , Tutunea-Fatan O. Remus , Bordatchev Evgueni V.
Published: September 2016

Retroreflectors (RR) represent optical elements whose primary functionality is to return to the incident light back to its originating source. While inverted cube-corner (ICC) geometry constitutes de facto standard in automotive lighting applications, other RR designs exist. Among them, right triangular prism (RTP) constitutes a viable alternative and therefore, the main intention of the present study was to demonstrate a fabrication means other than the ineffective conventional pin-bundling technology are possible.

To address this, a new ultraprecise single point inverted cutting (SPIC) technology — envisioned as a virtual combination between diamond turning and five-axis machining — was introduced as a viable manufacturing option for the fabrication of the RTP RR arrays. While simulation results seem to suggest a slight optical superiority of the RTP RR arrays produced through conventional, rather than SPIC approaches, experimental results have demonstrated that fabricating RTP RR prototypes is not only possible, but it can yield better retroreflective efficiencies when compared to state-of-the-art ICC-based automotive retroreflectors.
Pose-Dependent Dynamic Modeling and Analysis of Bi-Rotary Milling Head
Authors: Du Chao , Lu Dun , Zhang Jun , Zhang Huijie , Zhao Wanhua
Published: September 2016

Bi-rotary milling head is one of the core components of five-axis machining center and its dynamic characteristics directly affect the machining stability and accuracy. During the five-axis machining, the milling head would change the posture continuously. To facilitate rapid evaluation and optimization of the dynamic behavior of the bi-rotary milling head within the whole workspace, a multi-rigid-body dynamic model considering the flexible joint is established. The varying stiffness of the flexible joints affected by gravity and cutting force at different swing angles is analyzed. A parametric dynamic equation with posture parameters and physical parameters is finally deduced. The sensitive structural parameters on natural frequency and its fluctuation within the workspace are obtained by the sensitivity analysis. The theoretical and experimental results show that the dynamics of the bi-rotary milling head behave pose-dependent and the varying dynamics can be positive controlled by modifying sensitive structural parameters at the design stage.
Thermal Analysis on Directional Freezing of Nano Aqueous Suspensions in Graphene Aerogel 3D Printing Process
Authors: Zhao Guanglei , Zhou Chi , Lin Dong
Published: September 2016

This paper presented a novel 3D printing technique to fabricate graphene aerogel based on directional freezing. Thermal property of the graphene ink is one of key factors in this process which affects the material integrity and morphology as well as process efficiency and reliability. The major objective of this paper is to develop a heat transfer model to efficiently and reliably predict the temperature evolution of the printed materials and the waiting time between the layers for any input geometry. The simulation results show that the input geometry significantly affects the temperature evolution and waiting time. The proposed technique can not only improve the process efficiency and reliability, it can also serve as a flexible tool to predict and control the microstructure of the printed graphene aerogels.
Experimental and Numerical Framework for Study of Low Velocity Water Droplet Impact Dynamics
Authors: Mitchell B. R. , Nassiri A. , Locke M. R. , Klewicki J. C. , Korkolis Y. P. , Kinsey B. L.
Published: September 2016

Impacting water droplets are capable of eroding soil, rock, turbine blades and even high speed aircraft. Research has shown that high velocity water droplet impingement onto a solid workpiece can strip paint, remove rust, and serve as a machining operation. This technique is different from waterjet cutting as a train of water droplets are used to transport momentum to a workpiece rather than a continuous jet. Also, no abrasive medium is used which produces an environmentally friendly process. The exploitation of this water droplet impact phenomenon in industrial applications as a means to deform and remove material does not currently exist. If the impact dynamics of water droplets can be understood and controlled, then industries would have the framework upon which they could employ this phenomenon in novel manufacturing equipment. In this paper, as a starting point, the impact force of 2.9mm diameter water droplets impacting at low velocities (∼2m/s) was studied experimentally and numerically. A piezoelectric force sensor was used to measure the transient force of impacting water droplets, while numerical simulations were used to identify the solid-fluid interaction and develop the basis for high velocity (>100m/s) liquid droplet impact dynamics. Agreement was established between experimental observations and numerical predictions for the impact velocities considered.
Shape positional accuracy optimization via writing order correction
Authors: Lopez Gerald G. , Wood Steven A. , Metzler Meredith G. , Stammberger Stefan J. H. , McCay Roger S.
Published: September 2016

Shape positional accuracy is a ubiquitous challenge when writing critical features using electron beam (e-beam) lithography. Positional accuracy can be particularly important when patterning for dense pattern arrays often found in plasmonic device structures. These arrays contain structures critically placed within a few tens or hundreds of nanometers apart from one another, whereby poor positional accuracy on the same order of magnitude would impact overall device performance. The sources of positional accuracy are varied on an e-beam lithography system and can include, but are not limited to beam drift, surface charging, environmental noise, and temperature to name a few. This work demonstrates the impact of shape writing order on sub-100 nm features to tolerate these potential sources of shape positional errors. The shape positional accuracy of both proximity effect corrected (PEC) and non-PEC array patterns are studied using a 20 MHz fixed clock 50 keV Gaussian spot electron beam lithography system exposing at 1 nA with a 60 μm final aperture, and a 20 nm beam step size using 200 nm of ZEP520A from ZEON Chemicals atop a bulk Si substrate. The patterns are transferred via etch or metal deposition. The authors find that both pattern design and data preparation impacts positional accuracy by way of the designed shape order or the reshuffling of shapes, respectively. Resorting the shapes within the arrays allows the beam to continuously raster or meander through the array along the X- or Y-axis, row by row or column-by-column, respectively, while exposing abutting shapes yields optimal shape placement with a negligible impact on writing time.
Evaluation of the dose calculation accuracy for small fields defined by jaw or MLC for AAA and Acuros XB algorithms
Authors: Fogliata Antonella , Lobefalo Francesca , Reggiori Giacomo , Stravato Antonella , Tomatis Stefano , Scorsetti Marta , Cozzi Luca
Published: September 2016

Purpose

Small field measurements are challenging, due to the physical characteristics coming from the lack of charged particle equilibrium, the partial occlusion of the finite radiation source, and to the detector response. These characteristics can be modeled in the dose calculations in the treatment planning systems. Aim of the present work is to evaluate the MU calculation accuracy for small fields, defined by jaw or MLC, for anisotropic analytical algorithm (AAA) and Acuros XB algorithms, relative to output measurements on the beam central axis.

Methods

Single point output factor measurement was acquired with a PTW microDiamond detector for 6 MV, 6 and 10 MV unflattened beams generated by a Varian TrueBeam STx equipped with high definition‐MLC. Fields defined by jaw or MLC apertures were set; jaw‐defined: 0.6 × 0.6, 0.8 × 0.8, 1 × 1, 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm2; MLC‐defined: 0.5 × 0.5 cm2 to the maximum field defined by the jaw, with 0.5 cm stepping, and jaws set to: 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm2. MU calculation was obtained with 1 mm grid in a virtual water phantom for the same fields, for AAA and Acuros algorithms implemented in the Varian eclipse treatment planning system (version 13.6). Configuration parameters as the effective spot size (ESS) and the dosimetric leaf gap (DLG) were varied to find the best parameter setting. Differences between calculated and measured doses were analyzed.

Results

Agreement better than 0.5% was found for field sizes equal to or larger than 2 × 2 cm2 for both algorithms. A dose overestimation was present for smaller jaw‐defined fields, with the best agreement, averaged over all the energies, of 1.6% and 4.6% for a 1 × 1 cm2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 1 mm for both X and Y directions for AAA, and ESS = 1.5 and 0 mm for X and Y directions for Acuros. Conversely, a calculated dose underestimation was found for small MLC‐defined fields, with the best agreement averaged over all the energies, of −3.9% and 0.2% for a 1 × 1 cm2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 0 mm for both directions and both algorithms.

Conclusions

For optimal setting applied in the algorithm configuration phase, the agreement of Acuros calculations with measurements could achieve the 3% for MLC‐defined fields as small as 0.5 × 0.5 cm2. Similar agreement was found for AAA for fields as small as 1 × 1 cm2.
Inhibiting the inflammasome
Authors: Foley John F.
Published: September 2016

The kinase PKA phosphorylates and inactivates the NLRP3 inflammasome to restrain inflammation.
Association between
embB
Codon 306 Mutations, Phenotypic Resistance Profiles, and Genotypic Characterization in Clinical Mycobacterium tuberculosis Isolates from Hebei, China
Authors: Li Yanan , Wang Yuling , Zhang Zhi , Gao Huixia , Wang Haibin , Cao Jinfeng , Zhang Shumin , Liu Yuzhen , Lu Jianhua , Xu Zungui , Dai Erhei
Published: September 2016

Ethambutol (EMB) is an essential first-line drug for tuberculosis (TB) treatment. Nucleotide substitutions at
embB
codon 306 (
embB
306) have been proposed to be a potential marker for EMB resistance and a predictor of broad drug resistance in clinical
Mycobacterium tuberculosis
isolates. However, discordant findings about the association between
embB
306 mutations and EMB resistance were reported. Hebei Province is located in the Beijing-Tianjin-Hebei integration region in China; however, little information about the genetic diversity of the
embB
locus in this area is available. In this study, we sequenced the region surrounding
embB
306 (codons 207 to 445) in 62 ethambutol-resistant (EMB
r
) isolates, 214 ethambutol-susceptible isolates resistant to other first-line drugs (EMB
s
isolates), and 100 pan-sensitive isolates. Our data indicated that none of the pan-sensitive isolates showed mutations at
embB
306 and 63 drug-resistant isolates harbored
embB
306 substitutions, with these substitutions being found in 56.5% (35/62) of EMB
r
isolates and 13.1% (28/214) of EMB
s
isolates. A significant association between the
embB
306 mutation and resistance to isoniazid, rifampin, EMB, and multiple drugs was observed, and the rate of mutation of
embB
306 increased with increasing numbers of first-line drugs to which the isolates were resistant. The
embB
306 mutation is not the sole causative factor for EMB resistance, and the poor sensitivity limits its utility as a marker for drug-resistant TB. However, it may be a potential marker for broad drug resistance, especially for multidrug resistance. The mycobacterial interspersed repetitive unit–variable-number tandem-repeat profiles may serve as markers for predicting the
embB
306 substitutions that may occur in drug-resistant
M. tuberculosis
isolates under antimicrobial selection pressure.
Topical Decolonization Does Not Eradicate the Skin Microbiota of Community-Dwelling or Hospitalized Adults
Authors: Burnham Carey-Ann D. , Hogan Patrick G. , Wallace Meghan A. , Deych Elena , Shannon William , Warren David K. , Fritz Stephanie A.
Published: September 2016

Topical antimicrobials are often employed for decolonization and infection prevention and may alter the endogenous microbiota of the skin. The objective of this study was to compare the microbial communities and levels of richness and diversity in community-dwelling subjects and intensive care unit (ICU) patients before and after the use of topical decolonization protocols. We enrolled 15 adults at risk for
Staphylococcus aureus
infection. Community subjects (
n
= 8) underwent a 5-day decolonization protocol (twice daily intranasal mupirocin and daily dilute bleach-water baths), and ICU patients (
n
= 7) received daily chlorhexidine baths. Swab samples were collected from 5 anatomic sites immediately before and again after decolonization. A variety of culture media and incubation environments were used to recover bacteria and fungi; isolates were identified using matrix-assisted laser desorption ionization–time of flight mass spectrometry. Overall, 174 unique organisms were recovered. Unique communities of organisms were recovered from the community-dwelling and hospitalized cohorts. In the community-dwelling cohort, microbial richness and diversity did not differ significantly between collections across time points, although the number of body sites colonized with
S. aureus
decreased significantly over time (
P
= 0.004). Within the hospitalized cohort, richness and diversity decreased over time compared to those for the enrollment sampling (from enrollment to final sampling,
P
= 0.01 for both richness and diversity). Topical antimicrobials reduced the burden of
S. aureus
while preserving other components of the skin and nasal microbiota.
Pharmacodynamics of Ceftolozane Combined with Tazobactam against Enterobacteriaceae in a Neutropenic Mouse Thigh Model
Authors: Melchers M. J. , Mavridou E. , van Mil A. C. , Lagarde C. , Mouton J. W.
Published: September 2016

Ceftolozane is a new broad-spectrum cephalosporin and is combined with tazobactam to broaden the activity of ceftolozane against strains producing extended-spectrum beta-lactamases (ESBLs). We determined the pharmacodynamics (PD) of the combination in the neutropenic mouse thigh model to determine the optimal exposure of tazobactam. Treatment of CD-1 neutropenic mice was started 2 h after infection with ceftolozane every 2 h (q2h) alone or in combination with tazobactam at different dosing frequencies for 24 h, and the number of CFU in the thighs was determined before and after treatment. The maximum effect model was fit to the dose-response and the pharmacokinetic/PD index (PDI)-response to determine the PDI values for ceftolozane alone and ceftolozane in combination with tazobactam resulting in a static effect and a 1-log kill. The effect of tazobactam was dependent on the percentage of time that the free drug concentration remained above the concentration threshold (percent

f
T

>C

T

), whereby dosing q2h was more efficacious than dosing every 8 h (q8h), reducing the tazobactam daily dose by a factor 6.9 to 59.0 (
n
= 3 strains) to obtain a static effect. Using
R
2
as an indicator of the best fit of the percent

f
T

>C

T

-response relationships, the concentration threshold best correlating with the response varied from 0.5 to 2 mg/liter, depending on the strain. A similar result was obtained when the q2h and q8h regimens were analyzed. For all isolates tested, the mean

f
T

>C

T

for 0.5 mg/liter tazobactam was 28.2% (range, 17.5 to 45.8%) and 44.4% (range, 26.6 to 54.7%) for a static effect and a 1-log kill, respectively, at ceftolozane exposures that produced a ceftolozane concentration of 4 mg/liter (a concentration greater than the MIC) for 33.9 to 63.3% of a 24-h period under steady-state pharmacokinetic conditions. The main PDI that correlated with the effect of tazobactam was the

f
T

>C

T

achieved with a

C
T

of 0.5 mg/liter tazobactam.
Clonal Dissemination of Pseudomonas aeruginosa Sequence Type 235 Isolates Carrying
bla
IMP-6
and Emergence of
bla
GES-24
and
bla
IMP-10
on Novel Genomic Islands PAGI-15 and -16 in South Korea
Authors: Hong Jun Sung , Yoon Eun-Jeong , Lee Hyukmin , Jeong Seok Hoon , Lee Kyungwon
Published: September 2016

A total of 431
Pseudomonas aeruginosa
clinical isolates were collected from 29 general hospitals in South Korea in 2015. Antimicrobial susceptibility was tested by the disk diffusion method, and MICs of carbapenems were determined by the agar dilution method. Carbapenemase genes were amplified by PCR and sequenced, and the structures of class 1 integrons surrounding the carbapenemase gene cassettes were analyzed by PCR mapping. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed for strain typing. Whole-genome sequencing was carried out to analyze
P. aeruginosa
genomic islands (PAGIs) carrying the
bla
IMP-6
,
bla
IMP-10
, and
bla
GES-24
genes. The rates of carbapenem-nonsusceptible and carbapenemase-producing
P. aeruginosa
isolates were 34.3% (148/431) and 9.5% (41/431), respectively. IMP-6 was the most prevalent carbapenemase type, followed by VIM-2, IMP-10, and GES-24. All carbapenemase genes were located on class 1 integrons of 6 different types on the chromosome. All isolates harboring carbapenemase genes exhibited genetic relatedness by PFGE (similarity > 80%); moreover, all isolates were identified as sequence type 235 (ST235), with the exception of two ST244 isolates by MLST. The
bla
IMP-6
,
bla
IMP-10
, and
bla
GES-24
genes were found to be located on two novel PAGIs, designated PAGI-15 and PAGI-16. Our data support the clonal spread of an IMP-6-producing
P. aeruginosa
ST235 strain, and the emergence of IMP-10 and GES-24 demonstrates the diversification of carbapenemases in
P. aeruginosa
in Korea.
Transposition of Tn
125
Encoding the NDM-1 Carbapenemase in Acinetobacter baumannii
Authors: Bontron Séverine , Nordmann Patrice , Poirel Laurent
Published: September 2016

The
bla
NDM-1
gene encodes a carbapenemase that confers resistance to almost all β-lactams, including last-resort carbapenems. This is increasingly reported worldwide in nosocomial and community-acquired Gram-negative bacteria.
Acinetobacter baumannii
is an important opportunistic pathogen that is considered an intermediate reservoir for the
bla
NDM-1
gene. In this species, the
bla
NDM-1
gene is located within the Tn
125
composite transposon. The mechanism driving the mobility of Tn
125
has not yet been elucidated. Here we experimentally demonstrated the transposition of Tn
125
in
A. baumannii
. Systematic 3-bp duplication of the target site, being the signature of transposition, was evidenced. The target site consensus sequence for Tn
125
transposition was found to be GC enriched at the duplicated 3 bp and AT rich in the vicinity. Transposition frequency was not influenced by temperature changes or by exposure to subinhibitory concentrations of various antibiotics. This work is the first direct evidence of the functionality of a composite transposon in
A. baumannii
. It provides a mechanistic clue for the dissemination of the
bla
NDM-1
gene in
Acinetobacter
spp. and subsequently among
Enterobacteriaceae
.
Fluorescent Reporter DS6A Mycobacteriophages Reveal Unique Variations in Infectibility and Phage Production in Mycobacteria
Authors: Mayer Oren , Jain Paras , Weisbrod Torin R. , Biro Daniel , Ho Libby , Jacobs-Sera Deborah , Hatfull Graham F. , Jacobs William R.
Published: September 2016

Mycobacteriophage DS6A is unique among the more than 8,000 isolated mycobacteriophages due to its ability to form plaques exclusively on mycobacteria belonging to the
Mycobacterium tuberculosis
complex (MTBC). Speculation surrounding this specificity has led to unsupported assertions in published studies and patents that nontuberculous mycobacteria (NTM) are wholly resistant to DS6A infection. In this study, we identified two independent nonessential regions in the DS6A genome and replaced them with an mVenus-expressing plasmid to generate fluorescent reporter phages Φ
2
GFP12 and Φ
2
GFP13. We show that even though DS6A is able to form plaques only on MTBC bacteria, infection of various NTM results in mVenus expression in transduced cells. The efficiency of DS6A in delivering DNA varied between NTM species. Additionally, we saw a striking difference in the efficiency of DNA delivery between the closely related members of the
Mycobacterium abscessus
complex,
M. abscessus
and
Mycobacterium massiliense
. We also demonstrated that TM4 and DS6A, two phages that do not form plaques on
M. massiliense
, differ in their ability to deliver DNA, suggesting that there is a phage-specific restriction between mycobacterial species. Phylogenetic analysis reveals that the DS6A genome has a characteristically mosaic structure but provided few insights into the basis for the specificity for MTBC hosts. This study demonstrates that the inability of the MTBC-specific phage DS6A to form plaques on NTM is more complex than previously thought. Moreover, the DS6A-derived fluorophages provide important new tools for the study of mycobacterial biology.

IMPORTANCE
The coevolution of bacteria and their infecting phages involves a constant arms race for bacteria to prevent phage infection and phage to overcome these preventions. Although a diverse array of phage defense systems is well characterized in bacteria, very few phage restriction systems are known in mycobacteria. The DS6A mycobacteriophage is unique in the mycobacterial world in that it forms plaques only on members of the
Mycobacterium tuberculosis
complex. However, the novel DS6A reporter phages developed in this work demonstrate that DS6A can infect nontuberculous mycobacteria at various efficiencies. By comparing the abilities of DS6A and another phage, TM4, to infect and form plaques on various mycobacterial species, we can begin to discern new phage restriction systems employed within the genus.
The Adc/Lmb System Mediates Zinc Acquisition in Streptococcus agalactiae and Contributes to Bacterial Growth and Survival
Authors: Moulin Pauline , Patron Kévin , Cano Camille , Zorgani Mohamed Amine , Camiade Emilie , Borezée-Durant Elise , Rosenau Agnès , Mereghetti Laurent , Hiron Aurélia
Published: September 2016

The Lmb protein of
Streptococcus agalactiae
is described as an adhesin that binds laminin, a component of the human extracellular matrix. In this study, we revealed a new role for this protein in zinc uptake. We also identified two Lmb homologs, AdcA and AdcAII, redundant binding proteins that combine with the AdcCB translocon to form a zinc-ABC transporter. Expression of this transporter is controlled by the zinc concentration in the medium through the zinc-dependent regulator AdcR. Triple deletion of
lmb
,
adcA
, and
adcAII
, or that of the
adcCB
genes, impaired growth and cell separation in a zinc-restricted environment. Moreover, we found that this Adc zinc-ABC transporter promotes
S. agalactiae
growth and survival in some human biological fluids, suggesting that it contributes to the infection process. These results indicated that zinc has biologically vital functions in
S. agalactiae
and that, under the conditions tested, the Adc/Lmb transporter constitutes the main zinc acquisition system of the bacterium.

IMPORTANCE
A zinc transporter, composed of three redundant binding proteins (Lmb, AdcA, and AdcAII), was characterized in
Streptococcus agalactiae
. This system was shown to be essential for bacterial growth and morphology in zinc-restricted environments, including human biological fluids.
Human Coprolites as a Source for Paleomicrobiology
Authors: Appelt Sandra , Drancourt Michel , Le Bailly Matthieu
Published: September 2016

The paleomicrobiology of coprolites, which are fossilized fecal materials, has already yielded data about various organisms, including micro-eukaryotes, bacteria, and archaea, thus expanding our comprehension of ancient human dietary habits, gut microbiota, and intestinal and systemic infections. This mini-review briefly describes previous works and summarizes the main techniques used in handling coprolites and the findings obtained about ancient gut microbiota. Past intestinal and systemic infections are outlined.
Paleomicrobiology of Human Tuberculosis
Authors: Donoghue Helen D.
Published: September 2016

Tuberculosis is a significant global disease today, so understanding its origins and history is important. It is primarily a lung infection and is transmitted by infectious aerosols from person to person, so a high population density encourages its spread. The causative organism is
Mycobacterium tuberculosis
, an obligate pathogen in the
M. tuberculosis
complex that also contains closely related species, such as
Mycobacterium bovis
, that primarily infect animals. Typical bone lesions occur in about 5% of untreated infections. These can be recognized in historical and archaeological material, along with nonspecific paleopathology such as new bone formation (periostitis), especially on ribs. Based on such lesions, tuberculosis has been found in ancient Egypt, pre-Columbian America, and Neolithic Europe. The detection of
M. tuberculosis
ancient DNA (aDNA) by using PCR led to the development of the new field of paleomicrobiology. As a result, a large number of tuberculosis cases were recognized in mummified tissue and bones with nonspecific or no lesions. In parallel with these developments,
M. tuberculosis
cell wall lipid biomarkers have detected tuberculosis suggested by paleopathology and confirmed aDNA findings. In well-preserved cases, molecular typing has identified
M. tuberculosis
lineages and genotypes. The current interest in targeted enrichment, shotgun sequencing, and metagenomic analysis reveals ancient mixed infections with different
M. tuberculosis
strains and other pathogens. Identification of
M. tuberculosis
lineages from samples of known age enables the date of the emergence of strains and lineages to be calculated directly rather than by making assumptions on the rate of evolutionary change.
Past Bartonelloses
Authors: Fournier Pierre-Edouard
Published: September 2016

The origins of human infectious diseases have long fascinated scientists worldwide. Paleomicrobiology offers a unique access to the history of these infections and sheds light on ancient and historical epidemics. In this chapter, we review the paleomicrobiological evidence for
Bartonella
infections.
Characterization of the Funeral Groups Associated with Plague Epidemics
Authors: Tzortzis Stefan , Signoli Michel
Published: September 2016

There are several scenarios regarding how burial sites in archaeological contexts are discovered. We will focus on two scenarios according to the degree of historical knowledge regarding the studied sector. The excavation may be performed in a known funeral place or a highly suspected place (e.g., the interior or immediate exterior space in a religious monument or a parish cemetery). Also, the excavation of unexpected graves or graves discovered by chance may occur in places that had unknown or forgotten funeral purposes.
Sources of Materials for Paleomicrobiology
Authors: Aboudharam Gérard
Published: September 2016

The Paleomicrobiology establishes the diagnosis of ancient infectious diseases by studying ancient pathogens. This recent science also analyzes the evolution of these pathogens, virulence, and their adaptation to their habitat and their vectors. The DNA persists a long time after the death of an organism despite the chemical and enzymatic degradation. The possibility of sequencing bacterial, viral, parasitic and archaeal DNA molecules persists over time.

Various sources are used for these studies: frozen tissue and particularly human tissue are a exceptional source for the analysis because at very low temperatures, all biological activity is suspended. The coprolites are a source of choice for studying the human microbiome. Other sources, the ancient bones are the most abundant, however, they may contain only small amounts of DNA due to natural leaching. When the use of the tooth is possible, is a particularly interesting source because of its highly mineralized structure, which gives greater persistence than bone. The calcified tartar deposited on teeth is a source of interest for the study of oral microbiome.

All these sources are subject to precautions (gloves and masks hat) at the time of sampling to avoid cross contamination and also be listed in the most precise way because they are precious and rare.
Paleogenetics and Past Infections: the Two Faces of the Coin of Human Immune Evolution
Authors: Abi-Rached Laurent , Raoult Didier
Published: September 2016

With the advent of next-generation sequencing, paleogenetics has considerably expanded over the past few years and notably encompassed the characterization of the genomes of archaic humans who lived more than 30,000 years ago. These paleogenetics investigations have revealed that admixture between modern and archaic humans occurred, with Neanderthals having contributed to 1.5% to 2.1% of modern Eurasian genomes, and Denisovans to 3% to 6% of modern Melanesian genomes and to approximately 0.2% of modern Asian genomes. Although these contributions are modest, they played a major role in shaping immune gene families, such as the HLA class I genes, for which the archaic alleles now represent more than 50% of the alleles in Europe and Asia. Such a high frequency is consistent with these archaic HLA class I variants having been positively selected because of their protective effect against contagious and devastating epidemics, such as those due to the plague agent
Yersinia pestis
or to
Mycobacterium tuberculosis
, which is responsible for deadly tuberculosis. While the exact nature of the infectious agents that contributed to the selection of the archaic variants is unknown, we are entering an exciting period in which paleogenetics and paleomicrobiology data can be integrated to generate a clearer picture of how the immune system of modern populations was shaped and the role admixture and epidemics have played in such evolutions.
Early puberty in 11-year-old girls: Millennium Cohort Study findings
Authors: Kelly Yvonne , Zilanawala Afshin , Sacker Amanda , Hiatt Robert , Viner Russell
Published: September 2016

Objective

Early puberty in girls is linked to some adverse outcomes in adolescence and mid-life. We address two research questions: (1) Are socioeconomic circumstances and ethnicity associated with early onset puberty? (2) Are adiposity and/or psychosocial stress associated with observed associations?

Design

Longitudinal data on 5839 girls from the UK Millennium Cohort Study were used to estimate associations between ethnicity, family income, adiposity and psychosocial stress with a marker of puberty.

Main outcome measure

Reported menstruation at age 11 years.

Results

All quoted ORs are statistically significant. Girls in the poorest income quintile were twice as likely (OR=2.1), and the second poorest quintile nearly twice as likely (OR=1.9) to have begun menstruation compared with girls in the richest income quintile. Estimates were roughly halved on adjustment for Body Mass Index and markers of psychosocial stress (poorest, OR=1.5; second poorest, OR=1.5). Indian girls were over 3 times as likely compared with whites to have started menstruation (OR=3.5) and statistical adjustments did not attenuate estimates. The raised odds of menstruation for Pakistani (OR=1.9), Bangladeshi (OR=3.3) and black African (OR=3.0) girls were attenuated to varying extents, from about a third to a half, on adjustment for income and adiposity.

Conclusions

In contemporary UK, excess adiposity and psychosocial stress were associated with social inequalities in early puberty, while material disadvantage and adiposity were linked to ethnic inequalities in early puberty among girls.
Mitral valve replacement in neonatal endocarditis: time to discuss prevention strategies for Group B streptococcus disease
Authors: Salehian Sormeh , Rastogi Abhinav , Ghez Olivier , Burmester Margarita
Published: September 2016

Group B streptococcus (GBS) is recognised as one of the leading organisms in early-onset neonatal sepsis but is also a cause of late-onset GBS septicaemia, meningitis and rarely, infective endocarditis (IE). We report a case of a healthy term neonate who developed GBS septicaemia and meningitis having presented with parental concern and poor feeding. Subsequent identification and treatment of GBS resulted in the requirement for long-line intravascular access in order to administer antibiotic therapy. One week later, after repeated parental concern and symptoms of shortness of breath, the neonate presented to Accident and Emergency and subsequently a Paediatric Cardiorespiratory Intensive Care Unit where emergency resuscitation procedures were required and diagnosis of severe IE affecting the mitral valve was made. Mitral valve replacement was complicated with significant morbidity and prolonged hospitalisation. An innovative procedure to insert a Melody valve was successful.
Partnering with consumers to develop and evaluate a Vietnamese Dementia Talking-Book to support low health literacy: a qualitative study incorporating codesign and participatory action research
Authors: Goeman Dianne , Michael J , King J , Luu Huy , Emmanuel Claire , Koch S
Published: September 2016

Objective

The aim of the Vietnamese Dementia talking-book was to address low health literacy in older people of Vietnamese background living with dementia through the provision of an online resource to help individuals, their families and carers better understand and manage this condition and provide information about available dementia services.

Design

This qualitative study used codesign and participatory action research to develop and refine the talking-book in consultation with expert stakeholders, a consumer advocacy group and the Vietnamese community to assess its utility and ensure cultural and linguistic appropriateness and relevance.

Participants

59 members of the Vietnamese community, 11 stakeholders from community health services and ethnic agencies, consumer advocacy groups and the research team participated in the codesign and refinement of the talking-book. 22 members of the Vietnamese community appraised the final product.

Setting

Vietnamese community planned activity groups in the Western, Northern and Southern suburbs of Melbourne, Australia.

Results

Our codesign study outlines the process required to develop a Vietnamese Dementia Talking-Book resource partnering with consumers and expert stakeholders to identify consumer need, selection of the content and appropriate language level, construction of the book, measuring acceptability of the talking-book, modification based on feedback and production and dissemination. Feedback on the final version of the talking-book revealed widespread consensus that the book enhanced the knowledge of members of the Vietnamese community in regard to understanding dementia and navigation and accessing of available services.

Conclusions

This free internationally available online Vietnamese Dementia Talking-Book facilitates improved dementia-related health literacy in the Vietnamese community. The book also serves as a tool to facilitate the provision of care to Vietnamese people living with memory loss by assisting health professional staff to develop relationships with Vietnamese clients, their families and carers in a culturally appropriate manner.
Knee osteoarthritis in traumatic knee symptoms in general practice: 6-year cohort study
Authors: Kastelein Marlous , Luijsterburg Pim A J , Koster Ingrid M , Verhaar Jan A N , Koes Bart W , Vroegindeweij Dammis , Bierma-Zeinstra Sita M A , Oei Edwin H G
Published: September 2016

Aim

To identify degenerative knee abnormalities using MRI and radiography 6 years after knee trauma, their relation with persistent knee symptoms and baseline prognostic factors.

Methods

Adults (18–65 years) with incident traumatic knee symptoms visiting their general practitioner were followed up for 6 years and underwent baseline MRI and 6-year follow-up MRI and radiography. Logistic regression was used to analyse associations between various degenerative abnormalities on 6-year MRI and radiography, persistent knee symptoms and baseline prognostic factors for knee osteoarthritis (OA) on 6-year MRI.

Results

On 6-year radiography, 60% of patients showed no OA, 28% showed OA with Kellgren&Lawrence (K&L) grade 1 and 13% showed with K&L grade 2. On 6-year MRI, 55% of patients showed cartilage defect(s), 45% showed osteophyte(s), 36% showed subchondral cyst(s), 40% showed bone marrow oedema, 21% showed meniscal subluxation, 83% showed meniscal degeneration,11% showed effusion and 11% showed a Baker's cyst. Of these, most were significantly related with 6-year radiographic K&L grade, while only lateral cartilage defect(s), medial osteophyte(s) and medial meniscal subluxation were significantly related with persistent knee symptoms. 32% of patients showed new onset or progressive knee OA on 6-year MRI, for which age, history of non-traumatic knee symptoms and bone marrow oedema at baseline were independent prognostic factors.

Conclusions

Degenerative knee abnormalities on MRI are related to the K&L score; however, not all abnormalities are reflected in clinical outcome. Age, history of non-traumatic knee symptoms and bone marrow oedema predict knee OA 6 years after knee trauma, present in 32% of the patients.
Which unscheduled return visits indicate a quality-of-care issue?
Authors: Jiménez-Puente Alberto , del Río-Mata José , Arjona-Huertas José Luís , Mora-Ordóñez Begoña , Martínez-Reina Alfonso , Martínez del Campo Miguel , Nieto-de Haro Lourdes , Lara-Blanquer Antonio
Published: September 2016

Background

The rate of unscheduled return visits is often used as a quality-of-care indicator in EDs, although its validity is not yet fully established. Our aim was to identify the characteristics of return visits that may be attributed to problems in quality of care.

Methods

Retrospective paired review of medical charts in a random sample of return visits during the 72 hours following discharge from the ED in three hospitals of Andalusia, Spain in 2013. Charts were reviewed by senior medical physicians to determine which return visits reflected quality-of-care problems. Time frame for return visit, index and return visit acuity, disposition and diagnosis were compared with determine which variables were associated with a quality problem. Sensitivity and specificity for each variable to indicate a quality problem were determined.

Results

We studied the causes of 895 return visits, finding that 65 (7.3%) were due to inadequate quality of care in the index visit. Potentially avoidable return visits were more common in more severely ill patients, in those with greater severity in the return than in the index visit and in patients hospitalised after the return. The combination of this three variables presented sensitivity 66% and specificity 68% in identification of quality-related returns.

Conclusions

The overall level of return visits cannot be considered a valid indicator of quality of care. However, certain specific variables, including the level of severity of the patient's condition or the discharge destination following the return visits, could be considered valid in this respect.
First-lineHelicobacter pylorieradication therapies in countries with high and low clarithromycin resistance: a systematic review and network meta-analysis
Authors: Yeo Yee Hui , Shiu Sz-Iuan , Ho Hsiu J , Zou Biyao , Lin Jaw-Town , Wu Ming-Shiang , Liou Jyh-Ming , Wu Chun-Ying
Published: September 2016

Objective

To determine the optimal regimen of different first-lineHelicobacter pylorieradication therapies according to the clarithromycin resistance rate.

Design

Electronic search for articles published between January 2005 and April 2016. Randomised, controlled trials that reported the effectiveness of first-line eradication therapies in treatment-naïve adults were included. Two independent reviewers performed articles screening and data extraction. Network and traditional meta-analyses were conducted using the random effect model. Subgroup analyses were performed to determine the ranking of regimens in countries with high (>15%) and low (<15%) clarithromycin resistance. Data including adverse events and therapeutic cure rate were also extracted and analysed.

Results

117 trials (totally 32 852 patients) for 17H. pylorieradication regimens were eligible for inclusion. Compared with 7-day clarithromycin-based triple therapy, sequential therapy (ST) for 14 days had the highest effectiveness (OR=3.74, 95% CrI 2.37 to 5.96). ST-14 (OR=6.53, 95% CrI 3.23 to 13.63) and hybrid therapy (HY) for 10 days or more (OR=2.85, 95% CrI 1.58 to 5.37) represented the most effective regimen in areas with high and low clarithromycin resistance, respectively. The effectiveness of standard triple therapy was below therapeutic eradication rate in most of the countries. Longer duration was associated with higher eradication rate, but with a higher risk of events that lead to discontinuation.

Conclusions

ST and HY appeared to be the most effective therapies in countries with high and low clarithromycin resistance, respectively. The clinical decision for optimal regimen can be supported by referring to the rank ordering of relative efficacies stratified by local eradication rates, antibiotic resistance and safety profile.

Trial registration number

CRD42015025445.
Health insurance coverage, neonatal mortality and caesarean section deliveries: an analysis of vital registration data in Colombia
Authors: Houweling Tanja A J , Arroyave Ivan , Burdorf Alex , Avendano Mauricio
Published: September 2016

Background

Low-income and middle-income countries have introduced different health insurance schemes over the past decades, but whether different schemes are associated with different neonatal outcomes is yet unknown. We examined the association between the health insurance coverage scheme and neonatal mortality in Colombia.

Methods

We used Colombian national vital registration data, including all live births (2 506 920) and neonatal deaths (17 712) between 2008 and 2011. We used Poisson regression models to examine the association between health insurance coverage and the neonatal mortality rate (NMR), distinguishing between women insured via the contributory scheme (40% of births, financed through payroll and employer's contributions), government subsidised insurance (47%) and the uninsured (11%).

Results

NMR was lower among babies born to mothers in the contributory scheme (6.13/1000) than in the subsidised scheme (7.69/1000) or the uninsured (8.38/1000). Controlling for socioeconomic and demographic factors, NMRs remained higher for those in the subsidised scheme (OR 1.09, 95% CI 1.05 to 1.14) and the uninsured (OR 1.16, 95% CI 1.10 to 1.23) compared to those in the contributory scheme. These differences increased in models that additionally controlled for caesarean section (C-section) delivery. This increase was due to the higher fraction of C-section deliveries among women in the contributory scheme (49%, compared to 34% for the subsidised scheme and 28% for the uninsured).

Conclusions

Health insurance through the contributory system is associated with lower neonatal mortality than insurance through the subsidised system or lack of insurance. Universal health insurance may not be sufficient to close the gap in newborn mortality between socioeconomic groups.
Radial artery vasomotor function following transradial cardiac catheterisation
Authors: Mitchell A J , Mills N L , Newby D E , Cruden N L M
Published: September 2016

Aims

To determine the reproducibility of flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) in the assessment of radial artery vasomotor function, and to examine the effect of transradial catheterisation on radial artery injury and recovery.

Methods

Radial artery FMD and NMD were examined in 20 volunteers and 20 patients on four occasions (two visits at least 24 hours apart, with two assessments at each visit). In a further 10 patients, radial artery FMD was assessed in the catheterised arm prior to, at 24 hours and 3 months following cardiac catheterisation.

Results

There were no differences in baseline radial artery diameter (2.7±0.4 mm vs 2.7±0.4 mm), FMD (13.4±6.4 vs 12.89±5.5%) or NMD (13.6±3.8% vs 10.1±4.3%) between healthy volunteers and patients (p>0.05 for all comparisons). Mean differences for within and between day FMD were 2.53% (95% CIs −15.5% to 20.5%) and −4.3% (−18.3% to 9.7%) in patients. Compared to baseline, radial artery FMD was impaired at 24 hours (8.7±4.1% vs 3.9±2.9%, p=0.015) but not 3 months (8.7±4.1% vs 6.2±4.4, p=0.34) following transradial catheterisation.

Conclusions

Radial FMD is impaired early after transradial catheterisation but appears to recover by 3 months. While test–retest variability was demonstrated, our findings suggest that transradial access for cardiac catheterisation may afford a potential model of vascular injury and repair in vivo in man.