Searching for realism, structure and agency in Actor Network Theory.
Superficially, Actor Network Theory (ANT) and critical realism (CR) are radically opposed research traditions. Written from a realist perspective, this paper asks whether there might be a basis for finding common ground between these two traditions. It looks in turn at the questions of realism, structure, and agency, analysing the differences between the two perspectives and seeking to identify what each might learn from the other. Overall, the paper argues that there is a great deal that realists can learn from actor network theory; yet ANT remains stunted by its lack of a depth ontology. It fails to recognize the significance of mechanisms, and of their dependence on emergence, and thus lacks both dimensions of the depth that is characteristic of critical realism's ontology. This prevents ANT from recognizing the role and powers of social structure; but on the other hand, realists would do well to heed ANT's call for us to trace the connections through which structures are constantly made and remade. A lack of ontological depth also underpins ANT's practice of treating human and non-human actors symmetrically, yet this remains a valuable provocation to sociologists who neglect non-human entities entirely.


Impact of climate change on cold hardiness of Douglas-fir (Pseudotsuga menziesii): environmental and genetic considerations.
The success of conifers over much of the world's terrestrial surface is largely attributable to their tolerance to cold stress (i.e., cold hardiness). Due to an increase in climate variability, climate change may reduce conifer cold hardiness, which in turn could impact ecosystem functioning and productivity in conifer-dominated forests. The expression of cold hardiness is a product of environmental cues (E), genetic differentiation (G), and their interaction (G × E), although few studies have considered all components together. To better understand and manage for the impacts of climate change on conifer cold hardiness, we conducted a common garden experiment replicated in three test environments (cool, moderate, and warm) using 35 populations of coast Douglas-fir (Pseudotsuga menziesii var. menziesii) to test the hypotheses: (i) cool-temperature cues in fall are necessary to trigger cold hardening, (ii) there is large genetic variation among populations in cold hardiness that can be predicted from seed-source climate variables, (iii) observed differences among populations in cold hardiness in situ are dependent on effective environmental cues, and (iv) movement of seed sources from warmer to cooler climates will increase risk to cold injury. During fall 2012, we visually assessed cold damage of bud, needle, and stem tissues following artificial freeze tests. Cool-temperature cues (e.g., degree hours below 2 °C) at the test sites were associated with cold hardening, which were minimal at the moderate test site owing to mild fall temperatures. Populations differed 3-fold in cold hardiness, with winter minimum temperatures and fall frost dates as strong seed-source climate predictors of cold hardiness, and with summer temperatures and aridity as secondary predictors. Seed-source movement resulted in only modest increases in cold damage. Our findings indicate that increased fall temperatures delay cold hardening, warmer/drier summers confer a degree of cold hardiness, and seed-source movement from warmer to cooler climates may be a viable option for adapting coniferous forest to future climate.


Latent fingerprint chemical imaging by mass spectrometry.
Latent fingerprints (LFPs) potentially contain more forensic information than the simple identification of the subject; they may contain evidence of contacts with explosives or substances of abuse. Chemical information can also be useful in resolving overlapping LFPs from different individuals. We used desorption electrospray ionization mass spectrometry in an imaging mode to record compound-specific chemical fingerprints.


Tuning of the photoluminescence and up-conversion photoluminescence properties of single-walled carbon nanotubes by chemical functionalization.
Single-walled carbon nanotubes (SWNTs) were subjected to alkylation using alkyl bromide and alkyl dibromide, and the photoluminescence (PL) properties of the resulting alkylated SWNTs were characterized. Two new PL peaks were observed along with the intrinsic PL peak at 976 nm when alkyl bromide was used (SWNT-Bu: ∼1095 and 1230 nm, SWNT-Bn: 1104 and 1197 nm). In contrast, the use of α,α'-dibromo-o-xylene as an alkyl dibromide primarily resulted in only one new PL peak, which was observed at 1231 nm. The results revealed that the Stokes shift of the new peaks was strongly influenced by the addition patterns of the substituents. In addition, the time-resolved PL decay profiles of the alkylated SWNTs revealed that the PL peaks possessing a larger Stokes shift had longer exciton lifetimes. The up-conversion PL (UCPL) intensity of the alkylated SWNTs at excitation wavelengths of 1100 and 1250 nm was estimated to be ∼2.38 and ∼2.35 times higher than that of the as-dispersed SWNTs, respectively.


Sustained Neutralizing Antibodies 6 Months Following Infection in 376 Japanese COVID-19 Survivors.
Objective: There is scarce evidence regarding the long-term persistence of neutralizing antibodies among coronavirus disease 2019 (COVID-19) survivors. This study determined neutralizing antibody titers (NT50) and antibodies against spike protein (SP) or nucleocapsid protein (NP) antigens approximately 6 months after the diagnosis of COVID-19. Methods: COVID-19 survivors in Japan were recruited. Serum samples and data related to patients' characteristics and COVID-19 history were collected. NT50 and titers of antibodies against NP and SP antigens were measured at 20-32 weeks after the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results. Factors associated with NT50 were identified using the multivariable linear regression and the correlations among NT50 and titers of immunoglobulin G (IgG) and total immunoglobulins (Igs) against NP and SP were assessed by Spearman's correlation. Results: Among 376 participants (median [range] days after testing positive for SARS-CoV-2, 180 (147-224); median [range] years of age, 50 (20-78); 188 [50%] male), most tested positive for NT50 (n = 367, 98%), SP-IgG (n = 344, 91%), SP-total Ig (n = 369, 98%), NP-IgG (n = 314, 84%), and NP-total Ig (n = 365, 97%). Regression analysis indicated that higher BMI, fever, and the requirement of mechanical ventilation or extracorporeal membrane oxygenation were significantly associated with higher NT50. Anti-SP antibodies correlated moderately with NT50 (Spearman's correlation: 0.63 for SP IgG; 0.57 for SP-total Ig), while the correlation was weak for anti-NP antibodies (0.37 for NP IgG; 0.32 for NP-total Ig). Conclusions: Most COVID-19 survivors had sustained neutralizing antibodies and tested positive for SP-total Ig and NP-total Ig approximately 6 months after infection.


Unusual Early Recovery of a Critical COVID-19 Patient After Administration of Intravenous Vitamin C.
BACKGROUND Coronavirus disease 2019 (COVID-19) continues to spread, with confirmed cases now in more than 200 countries. Thus far there are no proven therapeutic options to treat COVID-19. We report a case of COVID-19 with acute respiratory distress syndrome who was treated with high-dose vitamin C infusion and was the first case to have early recovery from the disease at our institute. CASE REPORT A 74-year-old woman with no recent sick contacts or travel history presented with fever, cough, and shortness of breath. Her vital signs were normal except for oxygen saturation of 87% and bilateral rhonchi on lung auscultation. Chest radiography revealed air space opacity in the right upper lobe, suspicious for pneumonia. A nasopharyngeal swab for severe acute respiratory syndrome coronavirus-2 came back positive while the patient was in the airborne-isolation unit. Laboratory data showed lymphopenia and elevated lactate dehydrogenase, ferritin, and interleukin-6. The patient was initially started on oral hydroxychloroquine and azithromycin. On day 6, she developed ARDS and septic shock, for which mechanical ventilation and pressor support were started, along with infusion of high-dose intravenous vitamin C. The patient improved clinically and was able to be taken off mechanical ventilation within 5 days. CONCLUSIONS This report highlights the potential benefits of high-dose intravenous vitamin C in critically ill COVID-19 patients in terms of rapid recovery and shortened length of mechanical ventilation and ICU stay. Further studies will elaborate on the efficacy of intravenous vitamin C in critically ill COVID-19.


A systematic review of the exercise effect on bone health: the importance of assessing mechanical loading in perimenopausal and postmenopausal women.
The aims of this systematic review were to determine the general effects of exercise on areal bone mineral density (BMD) in perimenopausal and postmenopausal women, and to provide information on the most suitable bone-loading exercise regimens that may improve bone health in this population group. A computerized, systematic literature search was performed in the electronic databases PubMed, Web of Science, CINAHL, SPORTDiscus, and The Cochrane Library, from January 2005 to November 2015, to identify all randomized controlled trials related to exercise in perimenopausal and postmenopausal women. The initial search identified 915 studies, with a final yield of 10 studies. Only randomized controlled trials that examined the effects of exercise programs longer than 24 weeks in women aged 35 to 70 years were included. The 10 studies quantified at least BMD and described training variables adequately (training period, frequency, volume, intensity). Ten studies with moderate quality evidence (6.4 ± 1.8 points, range 4-9) were included. Significant changes in lumbar and femoral neck BMD were found mainly with high-impact exercise and whole body vibration interventions. While training effects must be interpreted with caution because of the heterogeneity of the protocols and exercises performed, this systematic review confirmed the effectiveness of impact exercises combined with other forms of training (vibration or strength training) to preserve BMD in perimenopausal and postmenopausal women. Despite the results possibly not representing a general dose-response relationship, we highlight the importance of quantifying loading intensity and frequency by means of accelerometry as these parameters are determinants for bone adaptation.


Determining molecular binding sites on human serum albumin by displacement of oleic acid.
An NMR method was developed for determining binding sites of small molecules on human serum albumin (HSA) by competitive displacement of (13)C-labeled oleic acid. This method is based on the observation that in the crystal structure of HSA complexed with oleic acid, two principal drug-binding sites, Sudlow's sites I (warfarin) and II (ibuprofen), are also occupied by fatty acids. In two-dimensional [(1)H,(13)C]heteronuclear single quantum coherence NMR spectra, seven distinct resonances were observed for the (13)C-methyl-labeled oleic acid as a result of its binding to HSA. Resonances corresponding to the major drug-binding sites were identified through competitive displacement of molecules that bind specifically to each site. Thus, binding of molecules to these sites can be followed by their displacement of oleic acids. Furthermore, the amount of bound ligand at each site can be determined from changes in resonance intensities. For molecules containing fluorine, binding results were further validated by direct observations of the bound ligands using (19)F NMR. Identifying the binding sites for drug molecules on HSA can aid in determining the structure-activity relationship of albumin binding and assist in the design of molecules with altered albumin binding.


Optomechanically induced transparency.
Electromagnetically induced transparency is a quantum interference effect observed in atoms and molecules, in which the optical response of an atomic medium is controlled by an electromagnetic field. We demonstrated a form of induced transparency enabled by radiation-pressure coupling of an optical and a mechanical mode. A control optical beam tuned to a sideband transition of a micro-optomechanical system leads to destructive interference for the excitation of an intracavity probe field, inducing a tunable transparency window for the probe beam. Optomechanically induced transparency may be used for slowing and on-chip storage of light pulses via microfabricated optomechanical arrays.


Risk of Hematologic Malignant Neoplasms From Abdominopelvic Computed Tomographic Radiation in Patients Who Underwent Appendectomy.
Whether computed tomography (CT) radiation is truly carcinogenic remains controversial. Large epidemiological studies that purportedly showed an association between CT radiation and carcinogenesis were limited by confounding by indication and reverse causation, because the reasons for CT examination were unknown. To measure the risk of hematologic malignant neoplasms associated with perioperative abdominopelvic CT radiation among patients who underwent appendectomy for acute appendicitis. This nationwide population-based cohort study used the National Health Insurance Service claims database in South Korea to assess 825 820 patients who underwent appendectomy for appendicitis from January 1, 2005, to December 31, 2015, and had no underlying risk factors for cancer. Patients were divided into CT-exposed (n = 306 727) or CT-unexposed (n = 519 093) groups. The study was terminated on December 31, 2017, and data were analyzed from October 30, 2018, to September 27, 2020. Perioperative abdominopelvic CT examination from 7 days before to 7 days after appendectomy. The primary outcome was the incidence rate ratio (IRR) of hematologic malignant neoplasms for both groups. The secondary outcomes were IRR of abdominopelvic organ cancers and IRR of all cancers. The lag period was 2 years for the primary outcome and 5 years for secondary outcomes. The IRRs were calculated using Poisson regression models with adjustment for age and sex. Among the study population of 825 820 patients (52.9% male; median age, 28 [interquartile range, 15-41] years), hematologic malignant neoplasms developed in 323 patients in the CT-exposed group during 1 486 518 person-years and 500 patients in the CT-unexposed group during 3 422 059 person-years. For all hematologic malignant neoplasms, the IRR for the CT-exposed vs CT-unexposed group was 1.26 (95% CI, 1.09-1.45; P = .002). In terms of individual categories of hematologic malignant neoplasms, the CT-exposed group had an elevated risk only for leukemia (IRR, 1.40 [98.75% CI, 1.04-1.87, adjusted by Bonferroni correction]; P = .005). There was no between-group difference in incidence rate of abdominopelvic organ cancers (IRR, 1.07 [95% CI, 1.00-1.15]; P = .06) and that of all cancers (IRR, 1.04 [95% CI, 0.99-1.09]; P = .14). This study controlled for reverse causation bias by defining the reasons for CT scan, and findings suggest that abdominopelvic CT radiation is associated with a higher incidence of hematologic malignant neoplasms. Efforts should be continued for judicious use of CT examinations.


Magnetohydrodynamic electrochemistry in the field of Nd-Fe-B magnets. Theory, experiment, and application in self-powered flow delivery systems.
Nd-Fe-B permanent magnets are easily available, powerful, and inexpensive and generate strong quantifiable convective effects during electrolysis, similar to those obtained with rotating electrodes or large electromagnets. The magnetic field of Nd-Fe-B magnets has been simulated numerically and mapped. Its most characteristic difference from the field of most commercial electromagnets is the presence of magnetic field gradients, which introduce additional body forces in the electrolytic solution and create new modes of mass transfer due to the attraction of electrogenerated radicals into areas of stronger field. The effect of those new forces on the radial distribution of the flow profile in the vicinity of the electrode has been monitored with generation-collection experiments and optical photography. The emerging utility of Nd-Fe-B magnets in systems of chemical interest is demonstrated with flow control and delivery devices, based on galvanic cells configured as self-powered magnetohydrodynamic pumps.


Differences in the kinematics of booster-seated pediatric occupants using two different car seats.
The objective of this article is to compare the performance of forward-facing child restraint systems (CRS) mounted on 2 different seats. Two different anthropomorphic test device (ATD) sizes (P3 and P6), using the same child restraint system (a non-ISOFIX high-back booster seat), were exposed to the ECE R44 regulatory deceleration pulse in a deceleration sled. Two different seats (seat A, seat B) were used. Three repetitions per ATD and mounting seat were done, resulting in a total of 12 sled crashes. Dummy sensors measured the head tri-axial acceleration and angular rate and the thorax tri-axial acceleration, all acquired at 10,000 Hz. A high-speed video camera recorded the impact at 1,000 frames per second. The 3D kinematics of the head and torso of the ATDs were captured using a high-speed motion capture system (1,000 Hz). A pair-matched statistical analysis compared the outcomes of the tests using the 2 different seats. Statistically significant differences in the kinematic response of the ATDs associated with the type of seat were observed. The maximum 3 ms peak of the resultant head acceleration was higher on seat A for the P3 dummy (54.5 ± 1.9 g vs. 44.2 ± 0.5 g; P =.012) and for the P6 dummy (56.0 ± 0.8 g vs. 51.7 ± 1.2 g; P =.015). The peak belt force was higher on seat A than on seat B for the P3 dummy (5,488.0 ± 198.0 N vs. 4,160.6 ± 63.6 N; P =.008) and for the P6 dummy (7,014.0 ± 271.0 N vs. 5,719.3 ± 37.4 N; P =.015). The trajectory of the ATD head was different between the 2 seats in the sagittal, transverse, and frontal planes. The results suggest that the overall response of the booster-seated occupant exposed to the same impact conditions was different depending on the seat used regardless of the size of the ATD. The differences observed in the response of the occupants between the 2 seats can be attributed to the differences in cushion stiffness, seat pan geometry, and belt geometry. However, these results were obtained for 2 particular seat models and a specific CRS and therefore cannot be directly extrapolated to the generality of vehicle seats and CRS.


Impaired cerebrovascular reactivity in multiple sclerosis.
Cerebrovascular reactivity (CVR) is an inherent indicator of the dilatory capacity of cerebral arterioles for a vasomotor stimulus for maintaining a spontaneous and instant increase of cerebral blood flow (CBF) in response to neural activation. The integrity of this mechanism is essential to preserving healthy neurovascular coupling; however, to our knowledge, no studies have investigated whether there are CVR abnormalities in multiple sclerosis (MS). To use hypercapnic perfusion magnetic resonance imaging to assess CVR impairment in patients with MS. A total of 19 healthy volunteers and 19 patients with MS underwent perfusion magnetic resonance imaging based on pseudocontinuous arterial spin labeling to measure CBF at normocapnia (ie, breathing room air) and hypercapnia. The hypercapnia condition is achieved by breathing 5% carbon dioxide gas mixture, which is a potent vasodilator causing an increase of CBF. Cerebrovascular reactivity was calculated as the percent increase of normocapnic to hypercapnic CBF normalized by the change in end-tidal carbon dioxide, which was recorded during both conditions. Group analysis was performed for regional and global CVR comparison between patients and controls. Regression analysis was also performed between CVR values, lesion load, and brain atrophy measures in patients with MS. A significant decrease of mean (SD) global gray matter CVR was found in patients with MS (3.56 [0.81]) compared with healthy controls (5.08 [1.56]; P = .001). Voxel-by-voxel analysis showed diffuse reduction of CVR in multiple regions of patients with MS. There was a significant negative correlation between gray matter CVR and lesion volume (R = 0.6, P = .004) and a significant positive correlation between global gray matter CVR and gray matter atrophy index (R = 0.5, P = .03). Our quantitative imaging findings suggest impairment in functional cerebrovascular pathophysiology, by measuring a diffuse decrease in CVR, which may be the underlying cause of neurodegeneration in MS.


Prostaglandins participate in the renal vasodilation due to hydralazine in dogs.
The authors studied the effects of bolus injections of hydralazine (500 micrograms) into the renal artery of chloralose-anesthetized dogs. In control dogs, hydralazine injection resulted in an increase in renal artery blood flow of 110 +/- 10.4 ml/min (53 +/- 4.7%) from 214 +/- 28 ml/min. In dogs that were pretreated with the alpha-1 adrenergic antagonist, prazosin (1 mg/kg), hydralazine injection increased renal blood flow by 95 +/- 22 ml/min (37 +/- 7.4%) from 253 +/- 19 ml/min, an increase not different from that found in control dogs. However, in dogs pretreated with indomethacin (5 mg/kg) or sodium meclofenamate (3 mg/kg), inhibitors of cyclooxygenase, hydralazine injection resulted in an increase in renal artery blood flow of only 44 +/- 5.3 ml/min (19 +/- 2.7%) from 235 +/- 23 ml/min, an increase significantly different from that in control dogs (P less than .05). The renal blood flow response to hydralazine injection developed slowly, reached a maximum in 20 min and was maintained for at least 1 hr. Arterial blood pressure, heart rate and descending aortic blood flow were not significantly changed after hydralazine injection. The authors conclude that hydralazine increases renal blood flow in dogs by a mechanism independent of alpha-1 adrenergic receptors and that this increase is, in large part, mediated by prostaglandin release.


Thermodynamics of N-H bond formation in bis(phosphine) molybdenum(ii) diazenides and the influence of the trans ligand.
A series of bis(phosphine) molybdenum(ii) diazenides [(dppe)2Mo(NNCy)(I)], [(dppe)2(CH3CN)Mo(NNCy)][BArF24] and [(dppe)2)(3,5-(CF3)2C6H3CN)Mo(NNCy)][BArF24] (dppe = 1,2-bis(diphenylphosphino)ethane; Cy = cyclohexyl; ArF24 = (3,5-(CF3)2C6H3)4) were synthesized and structurally characterized. Treatment of the diazenido complexes with a stoichiometric amount of [H(OEt2)2][BArF24] afforded the corresponding molybdenum(iv) hydrazido species [(dppe)2Mo(NNHCy)(I)][BArF24], [(dppe)2(CH3CN)Mo(NNHCy)][BArF24]2 and [(dppe)2(3,5-(CF3)2C6H3CN)Mo(NNHCy)][BArF24]2, enabling the study of N-H bond dissociation free energies (BDFEs) in the classical Chatt-type bis(phosphine) diazenide platform as a function of ligand (L) trans to the nitrogenous fragment. Deprotonation and electrochemical experiments established that the trans nitrile 3,5-(CF3)2C6H3CN afforded the least reducing molybdenum(iv) hydrazido complex in the series ( = -1.32 V vs. Fc/Fc+) with the most acidic N-H bond (pKa < 2.6, THF), whereas the ligands CH3CN ( = -1.60 V, pKa < 5.5) and I- ( = -2.03 V, pKa = 9.3) gave more reducing complexes with less acidic N-H bonds. Computational (DFT) studies confirm weak N-H bond strengths of 32.8 (L = I-), 35.4 (L = CH3CN) and 36.2 kcal mol-1 (L = 3,5-(CF3)2C6H3CN) in the hydrazido series.


The Impact of Peripheral Cooling on Chemotherapy-Induced Peripheral Neuropathy: An Integrative Review.
Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent, potentially long-lasting side effect of select chemotherapies. It contributes to suboptimal chemotherapy dosing, and its symptoms negatively impact patients' quality of life. To date, interventions to effectively prevent this toxicity have not been established, and interventions to treat CIPN have produced only modest results. The purpose of this integrative review is to examine the impact of regional cooling applied to distal extremities on the severity of CIPN. A literature review was performed using SCOPUS and PubMed databases. The search was not restricted by date but was restricted to English language. Forty-two articles were identified in the search, and six were included in the review after applying inclusion and exclusion criteria. Results related to protective effects from peripheral cooling against CIPN were variable. Four out of six studies demonstrated benefit of peripheral cooling in reducing the severity of CIPN. There was evidence to suggest that applying a relatively greater degree of cooling compared with a lesser degree may confer benefit in reducing the severity of CIPN. Both direct application of cooling and use of compression to achieve fingertip cooling showed potential benefit.


Successful Infection of Tick Cell Cultures of Rhipicephalus sanguineus (Tropical Lineage) with Ehrlichia canis.
There are two distinct lineages of ticks, Rhipicephalus sanguineus, in South America: tropical and temperate lineages. Only the tropical lineage is recognized as competent vector for Ehrlichia canis. The epidemiological data of canine monocytic ehrlichiosis is congruent with the distribution of the two lineages of R. sanguineus. Herein, we report the infection of R. sanguineus (tropical lineage) cell cultures with E. canis, after cryopreservation. R. sanguineus (tropical lineage) cell identity was confirmed by sequencing using a 16S rDNA gene fragment. Tick cell cultures were prepared in L-15B medium supplemented with 10%, 15%, and 20% Fetal Bovine Serum (FBS), and 10% of Tryptose Phosphate Broth (TPB). Cell cultures developed better at the concentration of 20% of FBS. Cultures in the fifth harvest (approximately 7 months later) were selected for the first infections. Optimal R. sanguineus cell growth and adhesion was observed (5.0 × 106 cells/mL, and the population doubling time every 57 h). Once infected with E. canis, the cultures were maintained in L-15B medium supplemented with 2% and 5% of FBS fortified with iron and 10% TPB. Infected cells were also cryopreserved. DNA was extracted from infected and noninfected cells and analyzed using quantitative real-time PCR targeting the E. canis-dsb gene. Primary culture of the fifth passage was infected by E. canis and it maintained the pathogen for at least 40 days before partial cell destruction. Subcultures of infected cells (fresh and cryopreserved cultures) onto new tick cell cultures were successful. The E. canis infection was confirmed by real-time PCR and light and transmission electron microscopy. The R. sanguineus (tropical lineage) cells infected with E. canis successfully infected new tick cell cultures, showing that these cells could be an alternative substrate for maintenance of this pathogen.


Methodological quality of systematic reviews on influenza vaccination.
There is a growing body of evidence on the risks and benefits of influenza vaccination in various target groups. Systematic reviews are of particular importance for policy decisions. However, their methodological quality can vary considerably. To investigate the methodological quality of systematic reviews on influenza vaccination (efficacy, effectiveness, safety) and to identify influencing factors. A systematic literature search on systematic reviews on influenza vaccination was performed, using MEDLINE, EMBASE and three additional databases (1990-2013). Review characteristics were extracted and the methodological quality of the reviews was evaluated using the assessment of multiple systematic reviews (AMSTAR) tool. U-test, Kruskal-Wallis test, chi-square test, and multivariable linear regression analysis were used to assess the influence of review characteristics on AMSTAR-score. Fourty-six systematic reviews fulfilled the inclusion criteria. Average methodological quality was high (median AMSTAR-score: 8), but variability was large (AMSTAR range: 0-11). Quality did not differ significantly according to vaccination target group. Cochrane reviews had higher methodological quality than non-Cochrane reviews (p=0.001). Detailed analysis showed that this was due to better study selection and data extraction, inclusion of unpublished studies, and better reporting of study characteristics (all p<0.05). In the adjusted analysis, no other factor, including industry sponsorship or journal impact factor had an influence on AMSTAR score. Systematic reviews on influenza vaccination showed large differences regarding their methodological quality. Reviews conducted by the Cochrane collaboration were of higher quality than others. When using systematic reviews to guide the development of vaccination recommendations, the methodological quality of a review in addition to its content should be considered.


A Blood Test for Alzheimer's Disease: Progress, Challenges, and Recommendations.
Ever since the discovery of APOEɛ4 around 25 years ago, researchers have been excited about the potential of a blood test for Alzheimer's disease (AD). Since then researchers have looked for genetic, protein, metabolite, and/or gene expression markers of AD and related phenotypes. However, no blood test for AD is yet being used in the clinical setting. We first review the trends and challenges in AD blood biomarker research, before giving our personal recommendations to help researchers overcome these challenges. While some degree of consistency and replication has been seen across independent studies, several high-profile studies have seemingly failed to replicate. Partly due to academic incentives, there is a reluctance in the field to report predictive ability, to publish negative findings, and to independently replicate the work of others. If this can be addressed, then we will know sooner whether a blood test for AD or related phenotypes with clinical utility can be developed.


A novel biosensor for quantitative monitoring of on-target activity of paclitaxel.
This study describes a system for quantifying paclitaxel activity using the C-terminus of α-tubulin as a biomarker. Following stabilization of microtubules with paclitaxel, a specific detyrosination reaction occurs at the C-terminus of α-tubulin which could be used to assess efficacy. A fluorescence resonance energy transfer (FRET) based biosensor was synthesized comprising a short peptide that corresponded to the C-terminus of α-tubulin, a fluorophore (Abz), and a quencher (Dnp). The fluorophore added to the end of the peptide can be released upon enzymatic detyrosination. In addition, a single fluorophore-tagged peptide was also conjugated to mesoporous silica nanoparticles to examine the feasibility of combining the drug with the peptide biomarker. As a proof of concept, we found that the degree of peptide cleavage, and therefore enzymatic activity, was directly correlated with exogenous bovine carboxypeptidase (CPA) an enzyme that mimics endogenous detyrosination. In addition, we show that cell lysates obtained from paclitaxel-treated cancer cells competed with exogenous CPA for biosensor cleavage in a paclitaxel dose-dependent manner. Our work provides strong evidence for the feasibility of combining paclitaxel with a novel biosensor in a multi-load nanoparticle.


Assessment of PDK4 and TTN gene variants in 48 Doberman Pinschers with dilated cardiomyopathy.
To evaluate the frequency of variants in the pyruvate kinase dehydrogenase 4 (PDK4) and titin (TTN) genes in a group of Doberman Pinschers with dilated cardiomyopathy (DCM) and to determine whether there were unique clinical attributes to each variant. 48 Doberman Pinschers with DCM. Doberman Pinschers with recently diagnosed DCM were identified, and genomic DNA from each was genotyped with a PCR assay for detection of PDK4 and TTN genetic variants. Dogs were grouped on the basis of whether they had the TTN variant alone, PDK4 variant alone, both variants, or neither variant. Descriptive statistics were compiled for dog age, body weight, and left ventricular dimensions and fractional shortening and for the presence of ventricular and supraventricular arrhythmias and heart failure. Results were compared across groups. Of the 48 dogs, 28 had the TTN variant alone, 10 had both variants, 6 had neither variant, and 4 had the PDK4 variant alone. The mean age was younger for dogs with the PDK4 variant alone, compared with other dogs. However, the number of dogs with the PDK4 variant alone was very small, and there was an overlap in age across groups. No other meaningful differences were detected across groups, and independent genotype-phenotype relationships were not identified. Although findings indicated that the TTN variant was most common, 6 dogs had neither variant, and this fact supported the concept of ≥ 1 other genetic contributor to DCM in Doberman Pinschers. Future studies are warranted to evaluate genotype-phenotype relationships in Doberman Pinschers with DCM.


Molecular population genetic analysis of a Streptococcus pyogenes bacteriophage-encoded hyaluronidase gene: recombination contributes to allelic variation.
Many strains of the human pathogenic bacterium Streptococcus pyogenes produce hyaluronidase, an enzyme that degrades hyaluronic acid, a major component of the extracellular matrix. Degradation of hyaluronic acid is thought to aid in host tissue invasion and dissemination of S. pyogenes. The molecular population genetics of the bacteriophage-encoded hyaluronidase gene (hyl) was analysed by sequencing the gene from 13 streptococcal strains representing seven well-differentiated multilocus enzyme electrophoretic types and eight M or T protein serotypes. Substantial levels of allelic polymorphism were identified, and the analysis found strong statistical evidence that recombinational processes have contributed to the generation of molecular variation in this gene. A 111 base pair segment of hyl encoding a collagenous motif, that may bind collagen, was absent in a serotype M14 isolate and 13 serotype M18 multilocus enzyme electrophoretic type 20 strains examined. The analysis provides a molecular population genetics framework for studies examining the role of naturally occurring hyaluronidase variation in host-pathogen interactions.


Detection of mutated K-ras DNA in urine, plasma, and serum of patients with colorectal carcinoma or adenomatous polyps.
Our previous studies demonstrated that urine contains DNA derived from the circulation and that this DNA originated, in part, from organ sites and tumors distal to the urinary tract. To explore the potential use of DNA from urine as compared to other body fluids as a source for circulating DNA for cancer detection, the DNA concentration and the frequency of detection of mutated Kristin-ras (K-ras) DNA in serum, plasma, and urine were examined. The concentration of DNA in the urine was similar to that in the serum, but the DNA concentration in plasma was significantly lower than in either urine or serum (P < 0.05). When DNA derived from 10 muL of body fluid was used in each mutation assay, the detection frequency of mutated K-ras DNA was comparable among serum, plasma, and urine. However, when DNA derived from 200 muL of body fluid was used, the incidence of detecting mutated K-ras DNA in urine was significant higher (95%) than in either serum (35%) or plasma (40%) (P < 0.0005), suggesting that inhibitory factors in serum/plasma may be more limiting than in urine. The use and practicality of urine as a source of circulating DNA for cancer detection are discussed.


Allelic expression imbalance at high-density lipoprotein cholesterol locus MMAB-MVK.
Genome-wide association studies (GWAS) have identified numerous loci associated with various complex traits for which the underlying susceptibility gene(s) remain unknown. In a GWAS for high-density lipoprotein-cholesterol (HDL-C) level, one strongly associated locus contains at least two biologically compelling candidates, methylmalonic aciduria cblB type (MMAB) and mevalonate kinase (MVK). To detect evidence of cis-acting regulation at this locus, we measured relative allelic expression of transcribed SNPs in five genes using human hepatocyte samples heterozygous for the transcribed SNP. If an HDL-C-associated SNP allele differentially regulates mRNA level in cis, samples heterozygous both for a transcribed SNP and an HDL-C-associated SNP should display allelic expression imbalance (AEI) of the transcribed SNP. We designed statistical tests to detect AEI in a comprehensive set of linkage disequilibrium (LD) scenarios between the transcribed SNP and an HDL-C-associated SNP (rs7298565) in phase unknown samples. We observed significant AEI of 22% in MMAB (P = 1.4 x 10(-13), transcribed SNP rs11067231), and the allele associated with lower HDL-C level was associated with greater MMAB transcript level. The same rs7298565 allele was also associated with higher MMAB mRNA level (P = 0.0081) and higher MMAB protein level (P = 0.0020). In contrast, MVK, UBE3B, KCTD10 and ACACB did not show significant AEI (P > or = 0.05). These data suggest MMAB is the most likely gene influencing HDL-C levels at this locus and demonstrate that measuring AEI at loci containing more than one candidate gene can prioritize genes for functional studies.


A combined 1H-NMR spectroscopy- and mass spectrometry-based metabolomic study of the PPAR-alpha null mutant mouse defines profound systemic changes in metabolism linked to the metabolic syndrome.
The mobilization of triacylglycerides from storage in adipocytes to the liver is a vital response to the fasting state in mammalian metabolism. This is accompanied by a rapid translational activation of genes encoding mitochondrial, microsomal, and peroxisomal beta-oxidation in the liver, in part under the regulation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha). A failure to express PPAR-alpha results in profound metabolic perturbations in muscle tissue as well as the liver. These changes represent a number of deficits that accompany diabetes, dyslipidemia, and the metabolic syndrome. In this study, the metabolic role of PPAR-alpha has been investigated in heart, skeletal muscle, liver, and adipose tissue of PPAR-alpha null mice at 1 mo of age using metabolomics. To maximize the coverage of the metabolome in these tissues, (1)H-NMR spectroscopy, magic angle spinning (1)H-NMR spectroscopy, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry were used to examine metabolites in aqueous tissue extracts and intact tissue. The data were analyzed by the multivariate approaches of principal components analysis and partial least squares. Across all tissues, there was a profound decrease in glucose and a number of amino acids, including glutamine and alanine, and an increase in lactate, demonstrating that a failure to express PPAR-alpha results in perturbations in glycolysis, the citric acid cycle, and gluconeogenesis. Furthermore, despite PPAR-alpha being weakly expressed in adipose tissue, a profound metabolic perturbation was detected in this tissue.


Kaposi's sarcoma-associated herpesvirus K-bZIP is a coregulator of K-Rta: physical association and promoter-dependent transcriptional repression.
Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus that has been implicated in the pathogenesis of Kaposi's sarcoma and B-cell neoplasms. The genomic organization of KSHV is similar to that of Epstein-Barr virus (EBV). EBV encodes two transcriptional factors, Rta and Zta, which functionally interact to transactivate EBV genes during replication and reactivation from latency. KSHV encodes a basic leucine zipper protein (K-bZIP), a homologue of EBV Zta, and K-Rta, the homologue of EBV Rta. EBV Rta and Zta are strong transcriptional transactivators. Although there is ample evidence that K-Rta is a potent transactivator, the role of K-bZIP as a transcriptional factor is much less clear. In this study, we report that K-bZIP modulates K-Rta function. We show that K-bZIP directly interacts with K-Rta in vivo and in vitro. This association is specific, requiring the basic domain (amino acids 122 to 189) of K-bZIP and a specific region (amino acids 499 to 550) of K-Rta, and can be detected with K-bZIP and K-Rta endogenously expressed in BCBL-1 cells treated with tetradecanoyl phorbol acetate. The functional relevance of this association was revealed by the observation that K-bZIP represses the transactivation of the ORF57 promoter by K-Rta in a dose-dependent manner. K-bZIP lacking the interaction domain fails to repress K-Rta-mediated transactivation; this finding attests to the specificity of the repression. Interestingly, this repression is not observed for the promoter of polyadenylated nuclear (PAN) RNA, another target of K-Rta; thus, repression is promoter dependent. Finally, we provide evidence that the modulation of K-Rta by K-bZIP also occurs in vivo during reactivation of the viral genome in BCBL-1 cells. When K-bZIP is overexpressed in BCBL-1 cells, the level of expression of ORF57 but not PAN RNA is repressed. These data support the model that one function of K-bZIP is to modulate the activity of the transcriptional transactivator K-Rta.


Cospeech gestures are a window into the effects of Parkinson's disease on action representations.
Parkinson's disease impairs motor function and cognition, which together affect language and communication. Cospeech gestures are a form of language-related actions that provide imagistic depictions of the speech content they accompany. Gestures rely on visual and motor imagery, but it is unknown whether gesture representations require the involvement of intact neural sensory and motor systems. We tested this hypothesis with a fine-grained analysis of cospeech action gestures in Parkinson's disease. Thirty-seven people with Parkinson's disease and 33 controls described 2 scenes featuring actions which varied in their inherent degree of bodily motion. In addition to the perspective of action gestures (gestural viewpoint/first- vs. third-person perspective), we analyzed how Parkinson's patients represent manner (how something/someone moves) and path information (where something/someone moves to) in gesture, depending on the degree of bodily motion involved in the action depicted. We replicated an earlier finding that people with Parkinson's disease are less likely to gesture about actions from a first-person perspective-preferring instead to depict actions gesturally from a third-person perspective-and show that this effect is modulated by the degree of bodily motion in the actions being depicted. When describing high-motion actions, the Parkinson's group were specifically impaired in depicting manner information in gesture and their use of third-person path-only gestures was significantly increased. Gestures about low-motion actions were relatively spared. These results inform our understanding of the neural and cognitive basis of gesture production by providing neuropsychological evidence that action gesture production relies on intact motor network function. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Influence of the type of management system on corticosterone transfer into eggs in laying hens.
The effect of free-range versus cage management system on corticosterone transfer into the eggs was studied in laying hens. Hungarian Yellow laying hens (age: 21 weeks, body weight: 2.0 +/- 0.5 kg) were divided into two groups in the spring: Group I, free-range keeping (n=15 layers, density: > 0.5 bird/m2) in outdoor runs, with continuous access to a commercial layer feed; Group II, hens kept in battery cages (n=17 layers, density: 2 birds/m2, natural light, continuous access to feed and water). Eggs were collected after a one-week adaptation period on days 2, 7 and 16. Corticosterone (CST) was extracted from homogenised egg samples using an ASE-200 Accelerated Solvent Extractor and then assayed by liquid chromatography linked with tandem mass spectrometry (LC-MS/MS) [Thermo Quest Surveyor high-performance liquid chromatography (HPLC) interfaced via Atmospheric Pressure Chemical Ionisation (APCI) ion source to Finnigan/Thermo Quest LCQ Deca MS/MS] using dexamethasone as internal standard with positive APCI ionisation. CST concentrations of whole eggs laid by free-range hens on days 2, 7 and 16 were 0.370 +/- 0.218, 0.259 +/- 0.066 and 0.915 +/- 0.745 ng x g(-1), respectively, while those of eggs laid by caged hens were 0.206 +/- 0.157, 0.223 +/- 0.165 and 0.184 +/- 0.110 ng x g(-1) at the above sampling times. It is concluded that in free-range laying hens the sharp changes of environmental weather conditions significantly increased the corticosterone content of eggs, while the environmentally controlled and closed battery cage management technology resulted in relatively uniform corticosterone concentrations in the whole eggs.


Apoptosis may be an early event of progestin therapy for endometrial hyperplasia.
The aim of this study was to investigate the role of apoptosis during progestin therapy for the treatment of endometrial hyperplasia. Pre- and posttreatment paraffin-embedded endometrial tissue samples from 19 women with endometrial hyperplasia were examined for changes in glandular cellularity and apoptotic activity related to the administration of progestins. Twelve patients were successfully treated with progestin therapy and 7 patients failed treatment. Glandular cellularity was assessed based on calculating the average number of cells per gland obtained on histologic examination of hematoxylin and eosin stained tissue sections. Apoptotic activity was assessed on the same tissue sections by counting the average number of apoptotic cells per 10 high power fields (hpf) using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. The effects of progesterone on apoptotic activity in a low-grade endometrial adenocarcinoma cell line (Ishikawa cells) was also examined using an ELISA cell death detection kit. Glandular cellularity significantly decreased with progestin therapy in both treatment outcome groups. The reduction in cells per gland was significantly greater in the group of successfully treated cases compared to the treatment failures (P = 0.005). However, within the successfully treated group, in situ detection of apoptotic cells using the TUNEL assay showed no statistical difference between pre- and posttreatment endometrial samples. Interestingly, a significant decrease in apoptosis was found in posttreatment samples of the group with persistent hyperplasia. The average number of apoptotic cells detected in 10 hpf was reduced from 7.9 prior to treatment to 3.1 after progestin therapy (P = 0.03). In the progesterone-treated Ishikawa cell line, an increase in apoptotic activity started at 24 h, reached a peak at 48 h, and continued up to 72 h of hormone treatment. At 48 h, apoptotic activity was 42.6% greater than in the untreated control (P = 0.04). By 72 h of progesterone treatment, apoptosis was 37.2% greater in the treated cells compared to the noninoculated cells (P = 0.04). Progestin-induced apoptosis may occur during the early period of treatment for endometrial hyperplasia. Compared to the fully responsive group, persistent endometrial hyperplasia may have intrinsically different molecular mechanisms in response to progestin therapy.


Comparative metabolism of 1-, 2-, and 4-nitropyrene by human hepatic and pulmonary microsomes.
Determining the capability of humans to metabolize the mononitropyrene (mono-NP) isomers 1-, 2-, and 4-NP and understanding which human cytochrome P450 (P450) enzymes are involved in their activation and/or detoxification is important in the assessment of individual susceptibility to these environmental carcinogens. We compared the ability of 15 human hepatic and 8 pulmonary microsomal samples to metabolize each of the three isomers. Human hepatic microsomes were competent in metabolizing all three isomers. Qualitatively similar metabolic patterns were observed, although at much lower levels, upon incubating mono-NP with pulmonary microsomes. Ring-oxidized metabolites (phenols and trans-dihydrodiols) were produced from all three isomers. However, the nitroreductive metabolism leading to the formation of aminopyrene was evident only with 4-NP. The role of specific P450 enzymes in the human hepatic microsomal metabolism of mono-NP was investigated by correlating the P450-dependent catalytic activities in each microsomal sample with the levels of individual metabolites formed by the same microsomes and by examining the effects of agents that can either inhibit or stimulate specific P450 enzymes in mono-NP metabolism. On the basis of these studies, we attribute most of the hepatic microsomal metabolism of 1- and 4-NP to P450 3A4, although a minor role for P450 1A2 cannot be ruled out. Specifically, P450 3A4 was responsible for the formation of 3-hydroxy-1nitropyrene from 1-NP and the formation of trans-9,10-dihydro-9,10dihydroxy-4-nitropyrene, 9(10)-hydroxy-4-nitropyrene, and 4-aminopyrene from 4-NP. None of the P450 enzymes examined (P450s 3A4, 1A2, 2E1, 2A6, 2D6, and 2C9) appeared to be involved in catalyzing the formation of trans-4,5-dihydro-4,5-dihydroxy-2-nitropyrene and 6-hydroxy-2-nitropyrene from 2-NP in human hepatic microsomes. These results, the first report on the comparative metabolism of mono-NP in humans, clearly demonstrate that the role of specific human P450 enzymes in catalyzing oxidative and reductive pathways of mono-NP is dependent upon the position of the nitro group.


Adsorption and inhibition of acetylcholinesterase by different nanoparticles.
Manufactured nanoparticles can be toxic via interactions with proteins and enzymes. Acetylcholinesterase (AChE) is a key enzyme present in the brain, blood and nervous system. Therefore, adsorption and inhibition of AChE by eight nanoparticles, SiO(2), TiO(2), Al(2)O(3), Al, Cu, Cu-C (carbon-coated copper), multi-walled carbon nanotubes (MWCNT) and single-walled carbon nanotubes (SWCNT), were examined. A modified Ellman assay was used to measure AChE activity because nanoparticles could adsorb the yellowish product, 5'-mercapto-2'-nitrobenzoic acid (5-MNBA) during the color development. Adsorption and inhibition rates by nanoparticles were estimated by decrease of AChE activities compared to controls. Carbon nanotubes had high affinity for AChE adsorption, the highest being SWCNT (94%). Nano SiO(2) and Al(2)O(3) showed the lowest adsorption. Inhibition by the tested nanoparticles was primarily caused by adsorption. However, Cu(2+) release in Cu and Cu-C nanoparticle suspensions caused 40% and 45% of AChE activity reduction, respectively. AChE inhibition by bulk Cu and activated carbon particles was also measured for comparison, showing that the inhibition by bulk particles was lower than their counterpart nanoparticles. For bulk Cu particles, AChE inhibition was primarily caused by dissolved ions, but mainly by adsorption for activated carbon. AChE inhibition by Cu, Cu-C, MWCNT and SWCNT had dose-response relationships, and their median inhibitory concentrations (IC(50)) were 4, 17, 156 and 96mgL(-1), respectively, showing that these nanoparticles may have neurotoxicity and AChE may have potential to be used as a biomarker for nanoparticles.


Endoscopic tri-modal imaging for detection of early neoplasia in Barrett's oesophagus: a multi-centre feasibility study using high-resolution endoscopy, autofluorescence imaging and narrow band imaging incorporated in one endoscopy system.
To investigate the diagnostic potential of endoscopic tri-modal imaging and the relative contribution of each imaging modality (i.e. high-resolution endoscopy (HRE), autofluorescence imaging (AFI) and narrow-band imaging (NBI)) for the detection of early neoplasia in Barrett's oesophagus. Prospective multi-centre study. Tertiary referral centres. 84 Patients with Barrett's oesophagus. The Barrett's oesophagus was inspected with HRE followed by AFI. All lesions detected with HRE and/or AFI were subsequently inspected in detail by NBI for the presence of abnormal mucosal and/or microvascular patterns. Biopsies were obtained from all suspicious lesions for blinded histopathological assessment followed by random biopsies. (1) Number of patients with early neoplasia diagnosed by HRE and AFI; (2) number of lesions with early neoplasia detected with HRE and AFI; and (3) reduction of false positive AFI findings after NBI. Per patient analysis: AFI identified all 16 patients with early neoplasia identified with HRE and detected an additional 11 patients with early neoplasia that were not identified with HRE. In three patients no abnormalities were seen but random biopsies revealed HGIN. After HRE inspection, AFI detected an additional 102 lesions; 19 contained HGIN/EC (false positive rate of AFI after HRE: 81%). Detailed inspection with NBI reduced this false positive rate to 26%. In this international multi-centre study, the addition of AFI to HRE increased the detection of both the number of patients and the number of lesions with early neoplasia in patients with Barrett's oesophagus. The false positive rate of AFI was reduced after detailed inspection with NBI.


Plasma-treated carbon-fiber microelectrodes for improved purine detection with fast-scan cyclic voltammetry.
Here, we developed N2 and O2 plasma-treated carbon-fiber microelectrodes (CFME) for improved purine detection with fast-scan cyclic voltammetry (FSCV). Plasma treatment affects the topology and functionality of carbon which impacts the electrode-analyte interaction. CFME's are less sensitive to purines compared to catecholamines. Knowledge of how the electrode surface drives purine-electrode interaction would provide insight into methods to improve purine detection. Here, plasma-treated CFME's with N2 and O2 plasma was used to investigate the extent to which the surface functionality and topology affects purine detection and to improve purine sensing with FSCV. On average, O2 plasma increased the oxidative current for adenosine and ATP by 6.0 ± 1.2-fold and 6.4 ± 1.6-fold, and guanosine and GTP by 2.8 ± 0.47-fold and 5.8 ± 1.4-fold, respectively (n = 9). The O2 plasma increased the surface roughness and oxygen functionality. N2 plasma increased the oxidative current for adenosine and ATP by 1.5 ± 0.15-fold and 1.9 ± 0.23-fold, and guanosine and GTP by 1.4 ± 0.20-fold and 1.5 ± 0.20-fold, respectively (n = 11). N2 plasma increased the nitrogen functionality with minimal increases in roughness. Both plasma treatments impacted purines more than dopamine. Langmuir isotherms revealed that both plasma gases impact the theoretical surface coverage and adsorption strength of purines at the electrode. Overall, we show that purine detection is improved at surfaces with increased surface roughness, and oxygen and amine functionality. Plasma-treated CFMEs could be used in the future to study the analyte-electrode interaction of other neurochemicals.


Cell surface membrane homeostasis and intracellular membrane traffic balance in mouse L929 cells.
We have developed a simple method for synchronizing L929 mouse fibroblasts. Cultured as monolayers, these cells stop growing at confluency and arrest at the end of the G1 phase. Upon seeding at low density, they enter the S phase simultaneously. Using these cells we then looked at the evolution of the surface membrane area during the cell cycle using the fluorescence membrane probe TMA-DPH. In contact with cells, this probe partitions between the membrane (probe fluorescent) and the external medium (non-fluorescent), delivering a signal proportional to the membrane area. This area was constant until just before mitosis, when it increased at once. With the same probe as an endocytic marker, we examined how this membrane homeostasis could be consistent with intracellular membrane trafficking. The study was limited to one selected period of the cell cycle (6-9 hours). We observed that 14% of the membrane endocytosed was not recycled, but was replaced at the cell surface by newly formed membrane from biosynthetic pathways. Brefeldin A modified the membrane traffic, but not the overall membrane homeostasis. The results are discussed in the framework of a maturation model.


Caloramator australicus sp. nov., a thermophilic, anaerobic bacterium from the Great Artesian Basin of Australia.
A strictly anaerobic, thermophilic bacterium, designated strain RC3T, was isolated from microbial mats colonizing thermal waters of a run-off channel formed by free-flowing waters from a bore well (registered no. 17263) of the Great Artesian Basin, Australia. The slightly curved rods (2.5-4.2x0.8-1.0 microm) of strain RC3T stained Gram-positive and grew optimally in tryptone-yeast extract-glucose medium at 60 degrees C (range 45-70 degrees C) and pH 7 (range pH 5-9). Strain RC3T grew poorly on yeast extract (0.2 %) but did not grow on tryptone (0.2 %) as a sole carbon source; yeast extract was required for growth on other energy sources, which included glucose, fructose, galactose, xylose, maltose, sucrose, raffinose, mannose, cellobiose, cellulose, starch, amylopectin, xylan, peptone, amyl media (Research Achievement), threonine and pyruvate but did not include arabinose, ribose, lactose, CM-cellulose, myo-inositol, mannitol, chitin, casein, formate, acetate, succinate, propionate, lactate, benzoate, glycerol, ethanol, Casamino acids, arginine, alanine, serine, glycine, glutamine, leucine, isoleucine, methionine or aspartate. The end products of glucose fermentation were ethanol and acetate. In the presence of 0.2 % yeast extract, iron(III), manganese(IV) and elemental sulfur were reduced but not sulfate, sulfite, thiosulfate, nitrate or nitrite. Iron(III) was also reduced in the presence of peptone, tryptone, amyl media, threonine and glycerol but not chitin, xylan, pectin, starch, pyruvate, acetate, benzoate, lactate, propionate, succinate, inositol, ethanol, mannitol, arginine, glutamine or serine. Strain RC3T was not able to utilize molecular hydrogen and/or carbon dioxide in the presence or absence of iron(III). In the presence of iron(III) and glycerol, increased concentrations of Fe(II) corresponded to increased cell numbers, demonstrating that strain RC3(T) was able to conserve energy to support growth from the reduction of Fe(III) to Fe(II). Chloramphenicol, streptomycin, tetracycline, penicillin and ampicillin and NaCl concentrations greater than 2 % inhibited growth. The G+C content of the DNA was 34+/-1 mol% as determined by the thermal denaturation (Tm) method. 16S rRNA gene sequence analysis indicated that strain RC3T was affiliated to Caloramator fervidus (95.8 % similarity to the type strain) and to other Caloramator species (average similarity of 91.6 %) within the phylum Firmicutes. On the basis of phylogenetic and phenotypic characteristics, it is proposed that strain RC3T should be classified in the genus Caloramator as a representative of a novel species, Caloramator australicus sp. nov. The type strain is RC3T (=JCM 1508T =KCTC 5601T).


Purified lymphocyte function-associated antigen 3 binds to CD2 and mediates T lymphocyte adhesion.
CD2 is a T lymphocyte glycoprotein that functions in adhesion of T lymphocytes and also as a putative receptor for activation signals. Functional data suggest that LFA-3, a widely distributed cell surface glycoprotein, may be the biological ligand of CD2. We have purified LFA-3 from human erythrocytes and characterized the purified protein functionally. LFA-3 bound specifically to CD2+ cells, and this binding was inhibited by CD2 mAb. Conversely, purified LFA-3 inhibited binding of CD2 mAb to cells, and the concentration required for this effect suggests that LFA-3 half-saturated CD2 at 1-5 nM LFA-3. Purified LFA-3 inhibited rosetting of human and sheep erythrocytes with CD2+ T lymphoma cells and T lymphocytes, and mediated aggregation of a CD2+ T lymphoma cell line. Purified LFA-3 reconstituted into planar membranes mediated efficient CD2-dependent adhesion of T lymphoblasts. These data demonstrate that LFA-3 is a ligand for CD2 and that LFA-3 can mediate T lymphocyte adhesion.


Insurance status and mortality among patients with AIDS.
The aim of the study was to evaluate risk factors for mortality, including health care insurance status, among patients with AIDS in the era of modern combination antiretroviral therapy (cART). This study was part of the prospective, multicentre, observational Longitudinal Study of the Ocular Complications of AIDS (LSOCA). Patients were classified as having private health care insurance, Medicare, Medicaid, or no insurance. Hazard ratios (HRs) for death were calculated using proportional hazards regression models and staggered entries, anchored to the AIDS diagnosis date. Among 2363 participants with AIDS, 97% were treated with cART. At enrolment, 31% of participants had private insurance, 29% had Medicare, 24% had Medicaid, and 16% were uninsured. Noninfectious, age-related diseases, such as hypertension, diabetes, and renal disease, were more frequent among persons with Medicare than among those with private insurance. Compared with those who were privately insured, mortality was greater among participants with Medicare [adjusted HR (HRadj ) 1.35; 95% confidence interval (CI) 1.08-1.67; P = 0.008]. Among participants with a suppressed HIV viral load, compared with those who were privately insured, HRadj values for mortality were 1.93 (95% CI 1.08-3.44; P = 0.02) for those with Medicare and 2.09 (95% CI 1.02-4.27; P = 0.04) for those with Medicaid. Mortality among initially uninsured participants was not significantly different from that for privately insured participants, but these participants typically obtained ART and insurance during follow-up. Compared with privately insured participants, time-updated HRadj values for mortality were 1.34 (95% CI 1.05-1.70; P = 0.02) for those with Medicare, 1.34 (95% CI 1.01-1.80; P = 0.05) for those with Medicaid, and 1.35 (95% CI 0.97-1.88; P = 0.05) for those who were uninsured. In persons with AIDS, compared with those with private insurance, those with public insurance had increased mortality, possibly as a result of a greater burden of noninfectious, age-related diseases.


Effects of in-season uphill sprinting on physical characteristics in semi-professional soccer players.
Soccer performance is determined by a number of physiological adaptations that can be altered by high intensity training. However, the effectiveness of using an uphill sprint based protocol has not been demonstrated for soccer players. We sought to determine the effectiveness of an in-season uphill sprint training (UST) programme on soccer related physiological outcomes. Fourteen male soccer players (age: 22±8 years, height: 1.81±8 m, body mass: 76±12 kg) underwent testing (5-10-5 agility drill, Yo-Yo Intermittent Recovery Test Level 1, leg and back dynamometry and 3 km time trial) at baseline and after 6 weeks of UST or normal activity. Participants were allocated to a control (N.=7) or UST (N.=7) group. The UST group took part in twice weekly training consisting of 10 x 10 sec sprints with 60s recovery on a 7% gradient for six weeks. The control group maintained normal activity patterns. 3 km time trial, strength, agility and Yo-Yo performance were all significantly improved pre to post following 6 weeks of UST (agility 3%, d=1.3; strength 10%, d=-3.2; VO2max 3%, d=-1.4; 3-km TT 4%, d=1.3). In the control group 3 km time trial, strength, agility and Yo-Yo performance remained unchanged after 6 weeks (agility 0.1%, d=-0.2; strength 2%, d=0.0; VO2max -0.1%, d=0.0; 3-km TT 1.3%, d=0.3). Therefore in-season short duration UST is an effective way to improve soccer fitness in a time efficient manner.


Evaluation of downscaled, gridded climate data for the conterminous United States.
Weather and climate affect many ecological processes, making spatially continuous yet fine-resolution weather data desirable for ecological research and predictions. Numerous downscaled weather data sets exist, but little attempt has been made to evaluate them systematically. Here we address this shortcoming by focusing on four major questions: (1) How accurate are downscaled, gridded climate data sets in terms of temperature and precipitation estimates? (2) Are there significant regional differences in accuracy among data sets? (3) How accurate are their mean values compared with extremes? (4) Does their accuracy depend on spatial resolution? We compared eight widely used downscaled data sets that provide gridded daily weather data for recent decades across the United States. We found considerable differences among data sets and between downscaled and weather station data. Temperature is represented more accurately than precipitation, and climate averages are more accurate than weather extremes. The data set exhibiting the best agreement with station data varies among ecoregions. Surprisingly, the accuracy of the data sets does not depend on spatial resolution. Although some inherent differences among data sets and weather station data are to be expected, our findings highlight how much different interpolation methods affect downscaled weather data, even for local comparisons with nearby weather stations located inside a grid cell. More broadly, our results highlight the need for careful consideration among different available data sets in terms of which variables they describe best, where they perform best, and their resolution, when selecting a downscaled weather data set for a given ecological application.


Maternal immunisation in developing countries.
Maternal immunisation could help to prevent the 2-3 million neonatal and early infant deaths that occur in the developing world each year. Determining the causes of neonatal and early infant deaths in developing countries is difficult as most occur at home. However, it is likely that at least half are due to infections, several of which might be prevented by maternal immunisation. Even in poor countries with few health facilities, a high percentage of pregnant women attend an antenatal clinic at least once during pregnancy. Thus, an effective delivery system for maternal immunisation already exists and, because of the success of maternal tetanus immunisation, this approach to the prevention of serious illness or death in young infants is widely accepted by the general population. However, the high prevalence of HIV and malaria found in pregnant women in some parts of the developing world, especially sub-Saharan Africa, could have an effect on the efficacy of maternal immunisation as both of these infections adversely affect placental function. Nevertheless, the potential of maternal immunisation to prevent early infant deaths in developing countries needs to be fully explored. The incidence of pneumococcal infections is high in many developing countries and about 25% of these infections occur at an age before protection could be anticipated following vaccination with a pneumococcal conjugate vaccine in infancy. Thus, a strong case can be made for a trial of the effectiveness of maternal immunisation with a pneumococcal vaccine in preventing serious illness or death in young infants in developing countries.


A 3-Center Study Reveals New Insights Into the Impact of Non-HLA Antibodies on Lung Transplantation Outcome.
The presence of antibodies to angiotensin type 1 receptor (AT1R) and endothelin type A receptor (ETAR) is associated with allograft rejection in kidney and heart transplantation. The aim of our study was to determine the impact of AT1R and ETAR antibodies on graft outcome in lung transplantation. Pretransplant and posttransplant sera from 162 lung recipients transplanted at 3 centers between 2011 and 2013 were tested for antibodies to AT1R and ETAR by the enzyme-linked immunosorbent assay (ELISA) assay. Clinical parameters analyzed were: HLA antibodies at transplant, de novo donor-specific antibodies (DSA), antibody-mediated rejection (AMR), acute cellular rejection, and graft status. Late AMR (median posttransplant day 323) was diagnosed in 5 of 36 recipients with de novo DSA. Freedom from AMR significantly decreased for those recipients with strong/intermediate binding antibodies to AT1R (P = 0.014) and ETAR (P = 0.005). Trends for lower freedom from acute cellular rejection were observed for recipients with pretransplant antibodies to AT1R (P = 0.19) and ETAR (P = 0.32), but did not reach statistical significance. Lower freedom from the development of de novo DSA was observed for recipients with antibodies detected pretransplant to AT1R (P = 0.054), ETAR (P = 0.012), and HLA-specific antibodies (P = 0.063). When the pretransplant antibody status of HLA-specific antibody (hazard ratio [HR], 1.69) was considered together with either strong binding to AT1R or ETAR, an increased negative impact on the freedom from the development of de novo DSA was observed (HR, 2.26 for HLA antibodies and ETAR; HR, 2.38 for HLA antibodies and ETAR). These results illustrate the increased negative impact when antibodies to both HLA and non-HLA antigens are present pretransplant.


Successful remission of late-life drinking problems: a 10-year follow-up.
This study sought to determine (1) the rate and predictors of long-term remission among a sample of untreated late-life problem drinkers and (2) whether successfully remitted older problem drinkers attain levels of functioning and life contexts comparable to those of lifetime nonproblem drinkers at a 10-year follow-up. We compared 140 older baseline problem drinkers who were successful in achieving long-term remission to 184 baseline problem drinkers whose drinking problems did not remit over the course of 10 years and to 339 lifetime nonproblem drinkers, on functioning and life contexts at baseline and at 4- and 10-year follow-ups. Being female, having more recent onset of drinking problems, fewer and less severe drinking problems, friends who approved less of drinking, and drinking less and drinking less frequently at baseline predicted long-term remission. In many regards, long-term remitted problem drinkers attained levels of functioning and life context similar to those of lifetime nonproblem drinkers. However, remitted problem drinkers continued to report more incipient drinking problems, depressive symptoms, health and financial stressors, psychoactive medication use, reliance on avoidance coping strategies and less social support from friends than did lifetime nonproblem drinkers at the 10-year follow-up. About a third (30%) of an untreated sample of late-life problem drinkers succeeded in attaining stable, long-term remission. The functioning and life contexts of untreated remitted problem drinkers improved significantly over time; however, some deficits persisted at follow-up.


Theoretical integration of user satisfaction and technology acceptance of the nursing process information system.
The nursing process system (NPS) is used to establish the nursing process involving assessment, diagnosis, planning, intervention, and evaluation in solving the health problems of patients. The factors influencing the use of the NPS by nurses were analyzed based on user satisfaction and technology acceptance within the 3Q (service quality, information quality, and system quality) model. In this cross-sectional quantitative study, the valid responses of 222 nurses to a questionnaire were obtained; these nurses worked at eight hospitals affiliated with public organizations in Taiwan. Structural equation modeling was used to analyze information quality, system quality, service quality, user satisfaction, perceived usefulness, perceived ease of use, perceived enjoyment, behavioral attitude, and intention after the nurses had used the NPS system for more than 1 month. Information quality, service quality, and system quality influenced user satisfaction. User satisfaction affected perceived usefulness, perceived ease of use, and perceived enjoyment and had the highest explanatory power (R2 = 0.75). Furthermore, perceived usefulness, perceived ease of use, and perceived enjoyment influenced behavioral attitude and intention to use the system. The proposed model explained 53% of the variance in the intention to use the NPS. The relationships between the variables of the 3Q model were successfully used to examine the intention of nurses toward using the NPS. Using the findings of this study, designers and programmers can comprehensively understand the perceptions of nurses and further improve the performance of the NPS.


Critical review of coupled flux formulations for clay membranes based on nonequilibrium thermodynamics.
Extensive research conducted over the past several decades has indicated that semipermeable membrane behavior (i.e., the ability of a porous medium to restrict the passage of solutes) may have a significant influence on solute migration through a wide variety of clay-rich soils, including both natural clay formations (aquitards, aquicludes) and engineered clay barriers (e.g., landfill liners and vertical cutoff walls). Restricted solute migration through clay membranes generally has been described using coupled flux formulations based on nonequilibrium (irreversible) thermodynamics. However, these formulations have differed depending on the assumptions inherent in the theoretical development, resulting in some confusion regarding the applicability of the formulations. Accordingly, a critical review of coupled flux formulations for liquid, current, and solutes through a semipermeable clay membrane under isothermal conditions is undertaken with the goals of explicitly resolving differences among the formulations and illustrating the significance of the differences from theoretical and practical perspectives. Formulations based on single-solute systems (i.e., uncharged solute), single-salt systems, and general systems containing multiple cations or anions are presented. Also, expressions relating the phenomenological coefficients in the coupled flux equations to relevant soil properties (e.g., hydraulic conductivity and effective diffusion coefficient) are summarized for each system. A major difference in the formulations is shown to exist depending on whether counter diffusion or salt diffusion is assumed. This difference between counter and salt diffusion is shown to affect the interpretation of values for the effective diffusion coefficient in a clay membrane based on previously published experimental data. Solute transport theories based on both counter and salt diffusion then are used to re-evaluate previously published column test data for the same clay membrane. The results indicate that, despite the theoretical inconsistency between the counter-diffusion assumption and the salt-diffusion conditions of the experiments, the predictive ability of solute transport theory based on the assumption of counter diffusion is not significantly different from that based on the assumption of salt diffusion, provided that the input parameters used in each theory are derived under the same assumption inherent in the theory. Nonetheless, salt-diffusion theory is fundamentally correct and, therefore, is more appropriate for problems involving salt diffusion in clay membranes. Finally, the fact that solute diffusion cannot occur in an ideal or perfect membrane is not explicitly captured in any of the theoretical expressions for total solute flux in clay membranes, but rather is generally accounted for via inclusion of an effective porosity, n(e), or a restrictive tortuosity factor, τ(r), in the formulation of Fick's first law for diffusion. Both n(e) and τ(r) have been correlated as a linear function of membrane efficiency. This linear correlation is supported theoretically by pore-scale modeling of solid-liquid interactions, but experimental support is limited. Additional data are needed to bolster the validity of the linear correlation for clay membranes.


Cinnamaldehyde Inhibits Staphylococcus aureus Virulence Factors and Protects against Infection in a Galleria mellonella Model.
Bacterial resistance to the available marketed drugs has prompted the search of novel therapies; especially in regards of anti-virulence strategies that aim to make bacteria less pathogenic and/or decrease their probability to become resistant to therapy. Cinnamaldehyde is widely known for its antibacterial properties through mechanisms that include the interaction of this compound with bacterial cell walls. However, only a handful of studies have addressed its effects on bacterial virulence, especially when tested at sub-inhibitory concentrations. Herein, we show for the first time that cinnamaldehyde is bactericidal against Staphylococcus aureus and Enterococcus faecalis multidrug resistant strains and does not promote bacterial tolerance. Cinnamaldehyde actions were stronger on S. aureus as it was able to inhibit its hemolytic activity on human erythrocytes and reduce its adherence to latex. Furthermore, cinnamaldehyde enhanced the serum-dependent lysis of S. aureus. In vivo testing of cinnamaldehyde in Galleria mellonella larvae infected with S. aureus, showed this compound improves larvae survival whilst diminishing bacterial load in their hemolymph. We suggest that cinnamaldehyde may represent an alternative therapy to control S. aureus-induced bacterial infections as it presents the ability to reduce bacterial virulence/survival without promoting an adaptive phenotype.


Assessment of the Potential Impact and Cost-effectiveness of Self-Testing for HIV in Low-Income Countries.
Studies have demonstrated that self-testing for human immunodeficiency virus (HIV) is highly acceptable among individuals and could allow cost savings, compared with provider-delivered HIV testing and counseling (PHTC), although the longer-term population-level effects are uncertain. We evaluated the cost-effectiveness of introducing self-testing in 2015 over a 20-year time frame in a country such as Zimbabwe. The HIV synthesis model was used. Two scenarios were considered. In the reference scenario, self-testing is not available, and the rate of first-time and repeat PHTC is assumed to increase from 2015 onward, in line with past trends. In the intervention scenario, self-testing is introduced at a unit cost of $3. We predict that the introduction of self-testing would lead to modest savings in healthcare costs of $75 million, while averting around 7000 disability-adjusted life-years over 20 years. Findings were robust to most variations in assumptions; however, higher cost of self-testing, lower linkage to care for people whose diagnosis is a consequence of a positive self-test result, and lower threshold for antiretroviral therapy eligibility criteria could lead to situations in which self-testing is not cost-effective. This analysis suggests that introducing self-testing offers some health benefits and may well save costs.


Repeated lumbar or ventricular punctures in newborns with intraventricular haemorrhage.
Although in recent years the percentage of preterm infants who suffer intraventricular haemorrhage (IVH) has reduced, posthaemorrhagic hydrocephalus (PHH) remains a serious problem with a high rate of cerebral palsy and no evidence-based treatment. Survivors often have to undergo ventriculoperitoneal shunt (VPS) surgery, which makes the child permanently dependent on a valve and catheter system. This carries a significant risk of infection and the need for surgical revision of the shunt. Repeated removal of cerebrospinal fluid (CSF) by either lumbar puncture, ventricular puncture, or from a ventricular reservoir in preterm babies with IVH has been suggested as a treatment to reduce the risk of PHH development. To determine the effect of repeated cerebrospinal fluid (CSF) removal (by lumbar/ventricular puncture or removal from a ventricular reservoir) compared to conservative management, where removal is limited to when there are signs of raised intracranial pressure (ICP), on reduction in the risk of permanent shunt dependence, neurodevelopmental disability, and death in neonates with or at risk of developing posthaemorrhagic hydrocephalus (PHH). We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3), MEDLINE via PubMed (1966 to 24 March 2016), Embase (1980 to 24 March 2016), and CINAHL (1982 to 24 March 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. RCTs and quasi-RCTs that compared serial removal of CSF (via lumbar puncture, ventricular puncture, or from a ventricular reservoir) with conservative management (removing CSF only when there were symptoms of raised ICP). Trials also had to report on at least one of the specified outcomes of death, disability, or shunt insertion. We extracted details of the participant selection, participant allocation and the interventions. We assessed the following outcomes: VPS, death, death or shunt, disability, multiple disability, death or disability, and CSF infection. We assessed the quality of the evidence using the GRADE approach. Four trials (five articles) met the inclusion criteria of this review; three were RCTs and one was a quasi-RCT; and included a total of 280 participants treated in neonatal intensive care units in the UK. The trials were published between 1980 and 1990. The studies were sufficiently similar regarding the research question they asked and the interventions that we could combine the trials to assess the effect of the intervention.Meta-analysis showed that the intervention produced no significant difference when compared to conservative management for the outcomes of: placement of hydrocephalus shunt (typical risk ratio (RR) 0.96, 95% confidence interval (CI) 0.73 to 1.26; 3 trials, 233 infants; I² statistic = 0%; moderate quality evidence), death (RR 0.88, 95% CI 0.53 to 1.44; 4 trials, 280 infants; I² statistic = 0%; low quality evidence), major disability in survivors (RR 0.98, 95% CI 0.81 to 1.18; 2 trials, 141 infants; I² statistic = 11%; high quality evidence), multiple disability in survivors (RR 0.9, 95% CI 0.66 to 1.24; 2 trials, 141 infants; I² statistic = 0%; high quality evidence), death or disability (RR 0.99, 95% CI 0.86 to 1.14; 2 trials, 180 infants; I² statistic = 0%; high quality evidence), death or shunt (RR 0.91, 95% CI 0.75 to 1.11; 3 trials, 233 infants; I² statistic = 0%; moderate quality evidence), and infection of CSF presurgery (RR 1.73, 95% CI 0.53 to 5.67; 2 trials, 195 infants; low quality evidence).We assessed the quality of the evidence as high for the outcomes of major disability, multiple disability, and disability or death. We rated the evidence for the outcomes of shunt insertion, and death or shunt insertion as of moderate quality as one included trial used an alternation method of randomisation. For the outcomes of death and infection of CSF presurgery, the quality of the evidence was low as one trial used an alternation method, the number of participants was too low to assess the objectives with sufficient precision, and there was inconsistency regarding the findings in the included trials regarding the outcome of infection of CSF presurgery. There was no evidence that repeated removal of CSF via lumbar puncture, ventricular puncture or from a ventricular reservoir produces any benefit over conservative management in neonates with or at risk for developing PHH in terms of reduction of disability, death, or need for placement of a permanent shunt.


Loyalty in Online Communities.
Loyalty is an essential component of multi-community engagement. When users have the choice to engage with a variety of different communities, they often become loyal to just one, focusing on that community at the expense of others. However, it is unclear how loyalty is manifested in user behavior, or whether certain community characteristics encourage loyalty. In this paper we operationalize loyalty as a user-community relation: users loyal to a community consistently prefer it over all others; loyal communities retain their loyal users over time. By exploring a large set of Reddit communities, we reveal that loyalty is manifested in remarkably consistent behaviors. Loyal users employ language that signals collective identity and engage with more esoteric, less popular content, indicating that they may play a curational role in surfacing new material. Loyal communities have denser user-user interaction networks and lower rates of triadic closure, suggesting that community-level loyalty is associated with more cohesive interactions and less fragmentation into subgroups. We exploit these general patterns to predict future rates of loyalty. Our results show that a user's propensity to become loyal is apparent from their initial interactions with a community, suggesting that some users are intrinsically loyal from the very beginning.


Dynamic light scattering with single-mode and multimode receivers.
Single-mode optical fibers provide the ideal receiver optics for dynamic light-scattering measurements. Theoretical analysis shows that with a single-mode fiber one can achieve a theoretical limit of 1 for the coherence factor while maintaining a high light-collection efficiency. In fact, the sensitivity of the single-mode receiver surpasses that of a classical two-pinhole setup with a coherence factor of 0.8 by a factor of 4 and the advantage increases rapidly when a still higher coherence factor is desired. In addition, a single-mode fiber receiver offers the possibility of working with an arbitrary large scattering volume and with an arbitrary working distance. All these features are also demonstrated experimentally by a remarkably simple apparatus that consists, essentially, of a commercial laser beam delivery assembly.


Complex Regional Pain Syndrome Type I Following Non-Orthopedic Surgery: Case Report and Narrative Review.
Complex regional pain syndrome type I (CRPS I)-or algodystrophy-is a rare disease that usually occurs after a traumatic event. It is characterized by typical clinical findings such as severe and disabling pain disproportionate to the injury, functional limitations, as well as sensory and vasomotor alterations. However, some people do not report any injury associated with algodystrophy onset in personal history. We describe the management of an unusual case of CRPS I which occurred during the long-term follow-up of percutaneous transluminal coronary angioplasty (PTCA) and performed a narrative review of algodystrophy in non-orthopedic surgery. A clinical case of a 44-year-old man with a spontaneous onset of CRPS I of the right ankle is presented. He did not refer to history of any memorable significant trigger event. Approximately 5 months before the onset of clinical manifestations, he received a PTCA via the right femoral approach. We suppose an association between CRPS and this procedure and propose a possible pathophysiologic mechanism. The patient was treated with intramuscular neridronate, which resulted in significant pain relief and improved his quality of life. A comprehensive clinical and instrumental evaluation in patients with CRPS is challenging but mandatory for a correct diagnosis. An extensive analysis of patient history is important for identifying any potential trigger event, including non-orthopedic procedures. Bone scan could have a pivotal role for improving diagnostic sensitivity and specificity in CRPS I. Neridronate was a safe and effective therapeutic approach for this patient, confirming the results of the high-quality evidence available.


Cognitive changes associated with cancer and cancer treatment: state of the science.
Cognitive impairment is a distressing, disruptive, and potentially debilitating symptom that can occur as a direct result of cancer or its treatment. National organizations have identified cognitive impairment as a challenge many survivors face and call for research to address this problem. Despite the priority, research is still relatively limited and questions remain unanswered about prevalence and impact on survivors, as well as coping strategies and effective treatment options available to address this potentially debilitating problem. The purpose of this article is to (a) analyze the prevalence and types of cognitive impairment that commonly affect survivors; (b) delineate the impact that cognitive impairment after cancer and cancer treatment has on self-esteem, social relationships, work ability, and overall quality of life among survivors; and (c) synthesize and appraise commonly used coping strategies used by survivors to address cognitive impairment and evidence-based interventions that may be incorporated into clinical practice. A comprehensive review and synthesis of the literature was conducted. Evidence-based interventions to address cognitive changes after cancer and cancer treatment are limited. However, emerging research has demonstrated that nonpharmacologic treatments, such as cognitive training, are likely to be effective.


Flood impacts in Keppel Bay, southern great barrier reef in the aftermath of cyclonic rainfall.
In December 2010, the highest recorded Queensland rainfall associated with Tropical Cyclone 'Tasha' caused flooding of the Fitzroy River in Queensland, Australia. A massive flood plume inundated coral reefs lying 12 km offshore of the Central Queensland coast near Yeppoon and caused 40-100% mortality to coral fringing many of the islands of Keppel Bay down to a depth of ∼8 m. The severity of coral mortality was influenced by the level of exposure to low salinity seawater as a result of the reef's distance from the flood plume and to a lesser extent, water depth and whether or not the reef faced the plume source. There was no evidence in this study of mortality resulting from pollutants derived from the nearby Fitzroy Catchment, at least in the short term, suggesting that during a major flood, the impact of low salinity on corals outweighs that of pollutants. Recovery of the reefs in Keppel Bay from the 2010/2011 Fitzroy River flood is likely to take 10-15 years based on historical recovery periods from a similar event in 1991; potentially impacting visitor numbers for tourism and recreational usage. In the meantime, activities like snorkeling, diving and coral viewing will be focused on the few shallow reefs that survived the flood, placing even further pressure on their recovery. Reef regeneration, restoration and rehabilitation are measures that may be needed to support tourism in the short term. However, predictions of a warming climate, lower rainfall and higher intensity summer rain events in the Central and Coastal regions of Australia over the next decade, combined with the current anthropogenic influences on water quality, are likely to slow regeneration with consequent impact on long-term reef resilience.


Factors Affecting Depth of Penetration in Microneedling- and Laser-Assisted Drug Delivery: The Importance of Timing of Topical Application.
Microneedling- and laser-assisted drug delivery are emerging techniques used to treat various conditions. However, key parameters affecting drug penetration remain unknown. This study aims to investigate the importance of timing of topical application, needle length, and device type for drug delivery. Skin harvested from cosmetic surgeries was treated with black ink applied before or after treatment with a microneedling pen (MP), roller, or fractional ablative CO2 laser, and incubated for different time intervals. Ink penetration was additionally tested using different needle lengths. Sandwich estimator was used for statistical analysis. Ink applied before MP penetrated deeper compared to ink applied afterward at 1 and 3 hours, and roller microneedling in both the ink-before and -after scenarios at 1, 3, and 6 hours (p < .05). Microneedling demonstrated lateral extension of ink beyond microchannels with increased ink penetration over time. CO2 laser demonstrated ink localization within microthermal zones without time-dependent increases in depth after 30 minutes. Ink penetration increases by 0.06 mm per 1 mm increase in needle length. Ink applied before MP results in the deepest penetration of ink. Microneedling offers unique advantages in transdermal delivery as its channels exhibit increasing penetration over time and lateral extension of product.


Individual and sex-specific differences in intrinsic growth rate covary with consistent individual differences in behaviour.
The evolutionary causes of consistent individual differences in behaviour are currently a source of debate. A recent hypothesis suggests that consistent individual differences in life-history productivity (growth and/or fecundity) may covary with behavioural traits that contribute to growth-mortality trade-offs, such as risk-proneness (boldness) and foraging activity (voraciousness). It remains unclear, however, to what extent individual behavioural and life-history profiles are set early in life, or are a more flexible result of specific environmental or developmental contexts that allow bold and active individuals to acquire more resources. Longitudinal studies of individually housed animals under controlled conditions can shed light on this question. Since growth and behaviour can both vary within individuals (they are labile), studying between-individual correlations in behaviour and growth rate requires repeated scoring for both variables over an extended period of time. However, such a study has not yet been done. Here, we repeatedly measured individual mass seven times each, boldness 40 times each and voracity eight times each during the first 4 months of life on 90 individually housed crayfish (Cherax destructor). Animals were fed ad libitum, generating a context where individuals can express their intrinsic growth rate (i.e. growth capacity), but in which bold and voracious behaviour is not necessary for high resource acquisition (crayfish can and do hoard food back to their burrow). We show that individuals that were consistently bold over time during the day were also bolder at night, were more voracious and maintained higher growth rates over time than shy individuals. Independent of individual differences, we also observed that males were faster-growing, bolder and more voracious than females. Our findings imply that associations between bold behaviour and fast growth can occur in unlimited food contexts where there is no necessary link between bold behaviour and resource acquisition - offering support for the 'personality-productivity' hypothesis. We suggest future research should study links between consistent individual differences in behaviour and life history under a wider range of contexts, in order to shed light on the role of biotic and abiotic conditions in the strength, direction and stability of their covariance.


Peripherally inserted central catheters in the neonatal period.
Peripherally inserted central catheters (PICC) have been extensively used in neonates. However, insertion of these thinnest catheters is a very delicate procedure associated with a high failure rate. In our Neonatal Surgical Intensive Care Unit, we developed a very easy new PICC insertion and evaluated the neonates treated with PICCs which were inserted by using our technique as well as catheter features such as success rate, number of insertion attempts, reason for removal and complications. Information was retrospectively collected on all 40 PICCs inserted at Kutahya Evliya Celebi Goverment Hospital and Dicle University Hospital during a 6-years period from September 2004 to September 2010. A total of 40 PICCs were inserted in 37 patients (26, 70% males, 11, 30% females) by using new technique. The median age of patients was 8.3 days (range 1 to 66 days) and the median weight of patients was 2365 g (range 600 to 5000 g). The vein most commonly accessed was long saphenous vein (85%). The length of PICCs in the body was 19.6 cm (range 5 cm to 30 cm). The tip was located in a central vein in all patients. Surgical abdomen was the most common cause for PICC insertion (38%). Duration of catheterization was 7.7±5.6 days (1-F 5.5 days, 2-F 8.6 days). Almost all of the PICCs were inserted successfully (40/42, success rate 95%) and in the first venipucture (36/42, 86%). Completion of therapy and removed after death were achieved with 87% of PICCs. Three minor complications were noted. Minor bleeding in the insertion site which was stopped via compression occurred in two neonates. Major complication was not seen. No deaths were directly attributed to PICCs use. The new insertion technique of the neonatal peripherally inserted central catheters may be one of the easiest and safest techniques, in comparison to previous techniques reported in the literature.


Experimental study of coexistence of multi-band OFDM-UWB and OFDM-baseband signals in long-reach PONs using directly modulated lasers.
Transmission of coexisting Orthogonal Frequency Division Multiplexing (OFDM)-baseband (BB) and multi-band OFDM-ultra-wideband (UWB) signals along long-reach passive optical networks using directly modulated lasers (DML) is experimentally demonstrated.When optimized modulation indexes are used, bit error ratios not exceeding 5 × 10⁻⁴ can be achieved by all (OFDM-BB and three OFDM-UWB sub-bands) signals for a reach of 100 km of standard single-mode fiber (SSMF) and optical signal-to-noise ratios not lower than firstname.lastname@example.com nm. It is experimentally shown that, for the SSMF reach of 100km, the optimized performance of coexisting OFDM-BB and OFDM-UWB signals is mainly imposed by the combination of two effects: the SSMF dispersion-induced nonlinear distortion of the OFDM-UWB signals caused by the OFDM-BB and OFDM-UWB signals, and the further degradation of the OFDM-UWB signals with higher frequency, due to the reduced DML bandwidth.