Early and intensive Motor Training for people with spinal cord injuries (the SCI-MT Trial): description of the intervention.

STUDY DESIGN: Descriptive. OBJECTIVES: The primary objective is to describe the intervention that will be provided in a large multi-centre randomised controlled trial titled: Early and Intensive Motor Training for people with Spinal Cord Injuries (the SCI-MT Trial). The secondary objective is to describe the strategies that will be used to operationalise and standardise the Motor Training provided to participants while keeping the intervention person-centred. METHODS: The paper focuses on the rationale and principles of Motor Training for people with spinal cord injuries (SCI). The description of the intervention is based on the Template for Intervention Description and Replication (TIDieR) checklist. Specifically, it addresses the following 6 criteria of the TIDieR checklist: why the effectiveness of Motor Training is being examined; what, how, where and when the Motor Training will be administered; and how much Motor Training will be provided. RESULTS: A detailed intervention manual has been developed to help standardise the delivery of the intervention. CONCLUSIONS: This paper describes the details of a complex intervention administered as part of a large randomised controlled trial. It will facilitate the subsequent interpretation of the trial results and enable the intervention to be reproduced in clinical practice and future trials.

The association of body mass index and odds of type 2 diabetes mellitus varies by race/ethnicity.

OBJECTIVE: This study aimed to examine the association between body mass index (BMI; weight [kilogram]/height2 [meter]) and type 2 diabetes mellitus (T2DM) among the largest three largest racial/ethnic groups in the United States. METHODS: We compiled 10 waves of the continuous National Health and Nutrition Examination Survey from 1999-2000 through 2017-2018. Participants (N = 45,514) were those who had data on BMI, HbA1c, and demographics. We estimated associations between BMI and prediabetes/T2DM odds for Black, Latine, and White participants. RESULTS: BMI was associated with 10% higher odds of prediabetes/T2DM vs. having normal HbA1c levels (odds ratio = 1.10, 95% confidence interval = 1.10-1.11) for Latine and White individuals. However, the association between BMI and prediabetes/T2DM was significantly weaker among Black individuals. When focusing on T2DM prevalence, the association with BMI for Black participants was even weaker (odds ratio = 0.97, 95% confidence interval = 0.95-0.98). CONCLUSIONS: The unstable associations between BMI and T2DM across race indicate that BMI has received unwarranted focus as a prime predictor of T2DM. Relying on BMI introduces bias in T2DM risk estimations especially in Black individuals. Focusing on BMI places the onus on individuals to change and increases weight stigma, which can worsen health outcomes. Instead, policymakers should focus on social determinants of T2DM and its concomitant racial/ethnic disparities.

Local anaesthetic transperineal (LATP) prostate biopsy using a probe-mounted transperineal access system: a multicentre prospective outcome analysis.

OBJECTIVES: To assess the feasibility of local anaesthetic transperineal (LATP) technique using a single-freehand transperineal (TP) access device, and report initial prostate cancer (PCa) detection, infection rates, and tolerability. PATIENTS AND METHODS: Observational study of a multicentre prospective cohort, including all consecutive cases. LATP was performed in three settings: (i) first biopsy in suspected PCa, (ii) confirmatory biopsies for active surveillance, and (iii) repeat biopsy in suspected PCa. All patients received pre-procedure antibiotics according to local hospital guidelines. Local anaesthesia was achieved by perineal skin infiltration and periprostatic nerve block without sedation. Ginsburg protocol principles were followed for systematic biopsies including cognitive magnetic resonance imaging-targeted biopsies when needed using the PrecisionPoint™ TP access device. Procedure-related complications and oncological outcomes were prospectively and consecutively collected. A validated questionnaire was used in a subset of centres to collect data on patient-reported outcome measures (PROMs). RESULTS: Some 1218 patients underwent LATP biopsies at 10 centres: 55%, 24%, and 21% for each of the three settings, respectively. Any grade PCa was diagnosed in 816 patients (67%), of which 634 (52% of total) had clinically significant disease. Two cases of sepsis were documented (0.16%) and urinary retention was observed in 19 patients (1.6%). PROMs were distributed to 419 patients, with a 56% response rate (n = 234). In these men, pain during the biopsy was described as either 'not at all' or 'a little' painful by 64% of patients. Haematuria was the most common reported symptom (77%). When exploring attitude to re-biopsy, 48% said it would be 'not a problem' and in contrast 8.1% would consider it a 'major problem'. Most of the patients (81%) described the biopsy as a 'minor or moderate procedure tolerable under local anaesthesia', while 5.6% perceived it as a 'major procedure that requires general anaesthesia'. CONCLUSION: Our data suggest that LATP biopsy using a TP access system mounted to the ultrasound probe achieves excellent PCa detection, with a very low sepsis rate, and is safe and well tolerated. We believe a randomised controlled trial comparing LATP with transrectal ultrasound-guided biopsy (TRUS) to investigate the relative trade-offs between each biopsy technique would be helpful.

Intermittent low dose carbon monoxide inhalation does not influence glucose regulation in overweight adults: a randomized controlled crossover trial.

NEW FINDINGS: What is the central question of this study? Low dose carbon monoxide (CO) inhalation plays a role in regulating proteins involved in glucose metabolism; does low dose CO improve glucose and insulin responses to an oral glucose tolerance test in overweight adults? What is the main finding and its importance? Five days of intermittent CO inhalation does not alter the glucose or insulin responses to ingestion of a glucose bolus in overweight adults. Low dose CO is utilized in various physiological assessment procedures; these findings allow researchers and clinicians to utilize these procedures without concern of altering glucose metabolism. ABSTRACT: Low dose carbon monoxide (CO) inhalation upregulates several proteins important for glucose metabolism. Such changes could be clinically significant and may be relevant to those who use CO as a research tool. We hypothesized that low dose CO inhalation would improve glucose and insulin responses to an oral glucose bolus in overweight humans. Eleven young adults (5 men, 6 women; body mass index: 25-35 kg m-2 ) were included in this randomized, placebo-controlled, single-blinded crossover study. Following screening, participants completed two 7-day protocols with a 4-week washout. Twenty-four hours prior to and following five consecutive days of either once daily CO (men: 1.2 ml (kg body mass)-1 ; women: 1.0 ml (kg body mass)-1 ) or placebo (room air) inhalation, participants underwent oral glucose tolerance tests (OGTT). For key outcome variables, there were no significant main effects or interactions across condition or time point (mean ± SD), including fasting glucose (mg dl-1 : pre-placebo: 85.2 ± 10.1; post-placebo: 82.9 ± 10.6; pre-CO: 83.6 ± 7.7; post-CO: 84.0 ± 9.0), 2 h post glucose (mg dl-1 : pre-placebo: 100.9 ± 20.0; post-placebo: 98.7 ± 13.1; pre-CO: 94.2 ± 23.2; post-CO: 94.4 ± 14.9), or the Matsuda index (pre-placebo: 16.1 ± 11.5; post-placebo: 20.3 ± 24.7; pre-CO: 15.6 ± 15.3; post-CO: 17.5 ± 16.8). In conclusion, 5 days of low dose CO administration did not influence glucose and insulin responses to an OGTT in overweight adults. Low dose CO inhalation is utilized in a variety of physiological assessment procedures; these findings allow researchers to utilize these procedures without concern of altering glucose metabolism.

Fetal ventricular strain in uncomplicated and selective growth-restricted monochorionic diamniotic twin pregnancies and cardiovascular response in pre-twin-twin transfusion syndrome.

OBJECTIVES: Our primary aim was to confirm whether intertwin discordance in ventricular strain and ductus venosus (DV) time intervals predicts twin-twin transfusion syndrome (TTTS). Secondary aims were to create gestational-age ranges for ventricular strain in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies without selective intrauterine growth restriction (sIUGR) and to characterize the relationship of ventricular strain with gestational age in MCDA twin pregnancies with sIUGR that did not develop TTTS. METHODS: In the period 2015-2018, we enrolled 150 MCDA twin pregnancies consecutively into this prospective, blinded study of global longitudinal left and right ventricular strain. With the observer blinded to twin pairing and pregnancy outcome, videoclips of the four-chamber view, which had been recorded during ultrasound surveillance in the usual window for development of TTTS (16-26 completed gestational weeks), underwent offline measurement of strain. Uncomplicated MCDA twin pregnancies, without sIUGR, were used to test the association between strain, gestational age and estimated fetal weight using mixed-effects multilevel regression. Inter-rater reliability was tested in 208 strain measurements in 31 fetuses from pregnancies which did not develop TTTS and within-fetus variation was assessed in 16 such fetuses, in which multiple four-chamber views were taken on the same day. The effect of sIUGR on strain in otherwise uncomplicated MCDA twin pregnancy was analyzed. MCDA twin pregnancies were defined as 'pre-TTTS' when, having been referred for TTTS evaluation, they did not satisfy Quintero staging criteria, but subsequently developed TTTS requiring laser treatment. MCDA pregnancies which did not develop TTTS comprised the 'non-TTTS' group. Cardiovascular parameters measured in these cases included tissue Doppler parameters and DV early filling time as a percentage of the cardiac cycle (DVeT%). Intertwin strain and DVeT% discordance was compared between non-TTTS and pre-TTTS cases, matched for gestational age. RESULTS: Paired strain data were available for intertwin comparison in 127/150 MCDA twin pregnancies, comprising 14 pre-TTTS and 113 non-TTTS pregnancies, after exclusions. Scans were collected at a median frame rate of 97 (range, 28-220) Hz. Laser therapy was performed at a median gestational age of 20.6 (range, 17.2-26.6) weeks. There were no group differences in right (RV) or left (LV) ventricular strain discordance between 68/113 non-TTTS and 13/14 pre-TTTS MCDA twin pregnancies < 20 completed gestational weeks (RV, P = 0.338; LV, P = 0.932). DVeT% discordance > 3.6% was found in eight of 13 pre-TTTS pregnancies. In non-TTTS pregnancies, the estimated variability in ventricular strain within each twin during the day was high (RV, 19.7; LV, 12.9). However, within each pair (intertwin variation), variability was low (RV, 5.5; LV, 2.9). Interclass correlation reflecting the proportion of total variability represented by the variability between twin pairs was low (RV, 0.22; LV, 0.18). Both RV (P < 0.001) and LV (P = 0.025) strain showed a negative association with gestational age. Among non-TTTS MCDA twin pregnancies, LV strain was, on average, higher by 1.83 in sIUGR compared with normally grown fetuses (P = 0.023), with no statistically significant difference in RV strain (P = 0.271). CONCLUSIONS: Although ventricular strain has been reported previously as a possible predictor of developing TTTS, in this blinded, prospective study, we found no significant intergroup differences in ventricular strain in pre-TTTS compared with age-matched non-TTTS MCDA twin pregnancies. We recommend using DVeT% discordance as a more practical screening tool in MCDA twin pregnancies. This study also provides new information on the changes with gestational age, and the biological and technical variation, of global longitudinal ventricular strain in uncomplicated MCDA twin pregnancies and those with isolated sIUGR. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The barriers to linkage and retention in care for women living with HIV in an high income setting where they comprise a minority group.

Women comprise a minority population of individuals living with HIV in Australia, and are often poorly represented in research and clinical trials so their needs remain largely unknown. Data suggests that they are diagnosed later than men and start antiretroviral therapy at a lower CD4 cell count. This raises the question whether there are sex specific barriers to linkage and retention in care. This study analyzed 484 surveys received from clinicians collecting demographic, virological, and reproductive health data along with perceived barriers to linkage and retention in care. Most women (67%) were estimated to have been linked into care within 28 days of diagnosis. For women who were not linked into care for more than 28 days, the most commonly reason cited was fear of disclosure to others, followed by fear of disclosure to their partner. The main reasons given for non-retention in care were related to transport, carer responsibilities, financial pressure, health beliefs and concern about stigma or disclosure.

First nations people's perspectives on barriers and supports for enhancing HPV vaccination: Foundations for sustainable, community-driven strategies.

OBJECTIVE: In Canada, Indigenous people have higher human papillomavirus (HPV) infection rates, lower screening rates for cervical cancer, and higher rates of invasive cancer, leading to worse cervical cancer-related outcomes than observed in non-Indigenous Canadian women. Lingering harms from European colonization drive these health inequities and create public health challenges. Policy guidance is needed to optimize HPV vaccination rates and, thereby, decrease the burden of HPV-related illness, including high-morbidity surgical procedures and chemo-radiotherapy. The Enhancing HPV Vaccination In First Nations Populations in Alberta (EHVINA) project focuses on First Nations, a diverse subset of recognized Indigenous people in Canada, and seeks to increase HPV vaccination among girls and boys living in First Nation communities. METHODS: Developing an effective strategy requires partnership with affected communities to better understand knowledge and perceptions about cancer, healthcare, and the HPV vaccine. A 2017 community gathering was convened to engage First Nations community members, health directors, and health services researchers in dialogue around unique barriers and supports to HPV vaccination in Alberta. Voices of community Elders, parents, health directors, and cancer survivors (n=24) are presented as qualitative evidence to help inform intervention design. RESULTS: Key findings from discussions indicate barriers to HPV vaccination include resource constraints and service infrastructure gaps, historical mistrust in healthcare systems, impacts of changing modes of communication, and community sensitivities regarding sexual health promotion. Supports were identified as strengthened inter-generational relationships in communities. CONCLUSIONS AND FUTURE DIRECTION: Ongoing dialogue and co-development of community-based strategies to increase HPV vaccine uptake are required. The identification of possible barriers to HPV vaccination in a Canadian Indigenous population contributes to limited global literature on this subject and may inform researchers and policy makers who work with Indigenous populations in other regions.

Routine germline BRCA1 and BRCA2 testing in patients with ovarian carcinoma: analysis of the Scottish real-life experience.

OBJECTIVE: To determine the rates of germline BRCA1 and BRCA2 mutations in Scottish patients with ovarian cancer, before and after a change in testing policy. DESIGN: Retrospective cohort study. SETTING: Four cancer/genetics centres in Scotland. POPULATION: Patients with ovarian cancer undergoing germline BRCA1 and BRCA2 (gBRCA1/2) sequencing before 2013 (under the 'old criteria', with selection based solely on family history), after 2013 (under the 'new criteria', with sequencing offered to newly presenting patients with non-mucinous ovarian cancer), and in the 'prevalent population' (who presented before 2013, but were not eligible for sequencing under the old criteria but were sequenced under the new criteria). METHODS: Clinicopathological and sequence data were collected before and for 18 months after this change in selection criteria. MAIN OUTCOME MEASURES: Frequency of germline BRCA1, BRCA2, RAD51C, and RAD51D mutations. RESULTS: Of 599 patients sequenced, 205, 236, and 158 were in the 'old criteria', 'new criteria', and 'prevalent' populations, respectively. The frequency of gBRCA1/2 mutations was 30.7, 13.1, and 12.7%, respectively. The annual rate of gBRCA1/2 mutation detection was 4.2 before and 20.7 after the policy change. A total of 48% (15/31) 'new criteria' patients with gBRCA1/2 mutations had a Manchester score of <15 and would not have been offered sequencing based on family history criteria. In addition, 20 patients with gBRCA1/2 were identified in the prevalent population. The prevalence of gBRCA1/2 mutations in patients aged >70 years was 8.2%. CONCLUSIONS: Sequencing all patients with non-mucinous ovarian cancer gives a much higher annual gBRCA1/2 mutation detection rate, with the frequency of positive tests still exceeding the 10% threshold upon which many family history-based models operate. TWEETABLE ABSTRACT: BRCA sequencing all non-mucinous cancer patients increases mutation detection five fold.

Deconstructing the evolutionary complexity between rust fungi (Pucciniales) and their plant hosts.

The rust fungi (Pucciniales) are the most speciose natural group of plant pathogens, members of which possess the most complex lifecycles in Fungi. How natural selection works on the Pucciniales has been the subject of several hypotheses in mycology. This study uses molecular age estimation using sequence data from multiple loci, and cophylogeny reconciliation analyses to test hypotheses regarding how the aecial and telial stages in the lifecycle of rust fungi may have differentially impacted their diversification. Molecular age estimates show that the timing of diversification in the Pucciniales correlates with the diversification of their gymnosperm and angiosperm hosts. Host reconciliation analyses suggest that systematic relationships of hosts from the aecial stage of the Pucciniales lifecycle better reflect the systematic relationships among the Pucciniales. The results demonstrate the relative importance of this stage on the overall evolution of the Pucciniales and supports hypotheses made by Leppik over half a century ago. This study represents the first evaluation of how different life stages in the Pucciniales shape the evolution of these fungi.

Sex-related differences in the thanatomicrobiome in postmortem heart samples using bacterial gene regions V1-2 and V4.

Recent studies have revealed distinct thanatomicrobiome (microbiome of death) signatures in human body sites after death. Thanatomicrobiome studies suggest that microbial succession after death may have the potential to reveal important postmortem biomarkers for the identification of time of death. We surveyed the postmortem microbiomes of cardiac tissues from 10 corpses with varying times of death (6-58 h) using amplicon-based sequencing of the 16S rRNA gene' V1-2 and V4 hypervariable regions. The results demonstrated that amplicons had statistically significant (P < 0·05) sex-dependent changes. Clostridium sp., Pseudomonas sp., Pantoea sp. and Streptococcus sp. had the highest enrichment for both V1-2 and V4 regions. Interestingly, the results also show that V4 amplicons had higher abundance of Clostridium sp. and Pseudomonas sp. in female hearts compared to males. In addition, Streptococcus sp. was solely found in male heart samples. The distinction between sexes was further supported by principle coordinate analysis, which revealed microbes in female hearts formed a distinctive cluster separate from male cadavers for both hypervariable regions. This study provides data that demonstrates that two hypervariable regions show discriminatory power for sex differences in postmortem heart samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings represent preliminary data of the first thanatomicrobiome investigation of a comparison between 16S rRNA gene V1-2 and V4 amplicon signatures in corpse heart tissues. The results demonstrated that V4 hypervariable region amplicons had statistically significant (P < 0·05) sex-dependent microbial diversity. For example, Streptococcus sp. was solely found in male postmortem heart tissues. Interestingly, the results also show that V4 amplicons had higher abundance of Clostridium sp. and Pseudomonas sp. in female heart tissues compared to males. The finding of Clostridium sp. supports the postmortem clostridium effect in corpse heart tissues.

Staphylococcus aureus bacteremia in immunosuppressed patients: a multicenter, retrospective cohort study.

Staphylococcus aureus bacteremia (SAB) causes significant morbidity and mortality. We assessed the disease severity and clinical outcomes of SAB in patients with pre-existing immunosuppression, compared with immunocompetent patients. A retrospective cohort investigation studied consecutive patients with SAB hospitalized across six hospitals in Toronto, Canada from 2007 to 2010. Patients were divided into immunosuppressed (IS) and immunocompetent (IC) cohorts; the IS cohort was subdivided into presence of one and two or more immunosuppressive conditions. Clinical parameters were compared between cohorts and between IS subgroups. A competing risk model compared in-hospital mortality and time to discharge. A total of 907 patients were included, 716 (79%) were IC and 191 (21%) were IS. Within the IS cohort, 111 (58%) had one immunosuppressive condition and 80 (42%) had two or more conditions. The overall in-hospital mortality was 29%, with no differences between groups (IS 32%, IC 28%, p = 0.4211). There were no differences in in-hospital mortality (sub-distribution hazard ratio [sHR] 1.17, 95% confidence interval [CI] 0.88-1.56, p = 0.2827) or time to discharge (sHR 0.94, 95% CI 0.78-1.15, p = 0.5570). Independent mortality predictors for both cohorts included hypotension at 72 h (IS: p < 0.0001, IC: p < 0.0001) and early embolic stroke (IS: p < 0.0001, IC: p = 0.0272). Congestive heart failure was a mortality predictor in the IS cohort (p = 0.0089). Fever within 24 h (p = 0.0092) and early skin and soft tissue infections (p < 0.0001) were survival predictors in the IS cohort. SAB causes significant mortality regardless of pre-existing immune status, but immunosuppressed patients do not have an elevated risk of mortality relative to immunocompetent patients.

H3N2 Canine Influenza Virus Infection in a Dog.

In 2015, H3N2 canine influenza emerged in dogs in the greater Chicago area. During this time, a 10-year-old German Shepherd dog presented to the referring veterinarian with lethargy and coughing that quickly progressed to death. This report describes the macroscopic and microscopic lesions and the molecular testing performed to identify the novel North American H3N2 strain of canine influenza. The larynx, pharynx, and trachea were covered by a fibrinonecrotic membrane. Bilaterally, the lungs had multifocal subpleural necrosis of the caudal lung lobes with hemorrhage, congestion, and pulmonary edema. Staphylococcus pseudointermedius was isolated from the lung. Mycoplasma cynos was identified by real-time polymerase chain reaction from nasal passages, oropharynx, larynx, trachea, and cranial lung lobes. The neuraminidase gene sequence from the influenza virus isolated obtained from this dog had ≥98% homology to the strain circulating in the Chicago area.

Clinical prediction rules in Staphylococcus aureus bacteremia demonstrate the usefulness of reporting likelihood ratios in infectious diseases.

Infectious diseases specialists often use diagnostic tests to assess the probability of a disease based on knowledge of the diagnostic properties. It has become standard for published studies on diagnostic tests to report sensitivity, specificity and predictive values. Likelihood ratios are often omitted. We compared published clinical prediction rules in Staphylococcus aureus bacteremia to illustrate the importance of likelihood ratios. We performed a narrative review comparing published clinical prediction rules used for excluding endocarditis in S. aureus bacteremia. Of nine published clinical prediction rules, only three studies reported likelihood ratios. Many studies concluded that the clinical prediction rule could safely exclude endocarditis based on high sensitivity and high negative predictive value. Of the studies with similar high sensitivity and high negative predictive value, calculated negative likelihood ratios were able to differentiate and identify the best clinical prediction rule for excluding endocarditis. Compared to sensitivity, specificity and predictive values, likelihood ratios can be more directly used to interpret diagnostic test results to assist in ruling in or ruling out a disease. Therefore, a new standard should be set to include likelihood ratios in reporting of diagnostic tests in infectious diseases research.

Collagen-like peptide sequences inhibit bacterial invasion of root dentine.

AIM: To investigate the effects of peptides derived from the sequence of collagen to inhibit penetration of human or bovine dentine by species of streptococci and enterococci. METHODOLOGY: Blocks of human or bovine root dentine were infected for 14 days with bacterial cultures, in the presence or absence of various collagen-like peptide sequences. Invasion of dentinal tubules was determined from microscopic images of histochemically stained dentine thin sections. Extent of invasion was expressed as tubule invasion index (TI), or tubule invasion factor (TIF) which, in addition to the density of invasion, took into account the depth of invasion. Data were analysed by two-way anova. RESULTS: Streptococcus gordonii, Streptococcus mutans and Enterococcus faecalis were associated with heavy invasion (TI >2.5, TIF >4) of human or bovine root dentinal tubules, with E. faecalis being the most penetrative. Incorporation of peptides Gly-Pro-Ala or Gly-Pro-Hyp into the in vitro model system significantly reduced (P < 0.05) dentine invasion by the three species of highly invasive organisms. Inhibition of bacterial invasion by the peptides was dose dependent, and the peptides did not inhibit bacterial growth in culture. CONCLUSION: Specific collagen-like peptide sequences inhibited the invasion of dentine in vitro by a range of oral bacteria. The peptides likely act as competitive inhibitors blocking bacterial collagen receptors and could potentially allow for target-specific control of dentine infections.

Forkhead box protein 3(+) regulatory T cells and Helios(+) subset in perinatally acquired HIV.

Forkhead box protein 3 (FoxP3)(+) regulatory T cells (Tregs ) are important not only in regulating the development of autoimmune conditions, but also in chronic infectious diseases. Given their cardinal function in suppressing immune activation, research has focused upon whether they play a detrimental role in chronic infections, particularly HIV. While the role of Tregs in HIV has been investigated intensively, it remains an unresolved topic. However, it is generally accepted that Tregs are susceptible to HIV infection and are preferentially preserved over conventional CD4(+) T cells. It is unknown whether the peripheral-induced or the thymic-derived Tregs are more susceptible to HIV cytotoxicity. It has been recognized that Tregs can be segregated into two subsets based on Helios expression, with the vast majority being Helios(+) . This study examines the impact of HIV infection on total Tregs and their Helios subsets in a perinatal-acquired HIV-infected paediatric population. The finding indicates a selective expansion or survival of Tregs in association with CD4 depletion and increased viraemia. The Helios(+) and Helios(-) subsets within Tregs appear to be equally affected. However, the Helios(+) Tregs seem to be more preserved in patients with low CD4(+) ≤ 25% and detectable plasma HIV RNA >20 copies/ml. In this group, the frequencies of Tregs are increased, but their numbers appear insufficient to restrain immune activation. In conclusion, our findings suggest that both Helios subsets of Tregs are susceptible to HIV infection and are preferentially preserved compared to conventional CD4(+) T cells.

Two-dimensional normal-state quantum oscillations in a superconducting heterostructure.

Semiconductor heterostructures provide an ideal platform for studying high-mobility, low-density electrons in reduced dimensions. The realization of superconductivity in heavily doped diamond, silicon, silicon carbide and germanium suggests that Cooper pairs eventually may be directly incorporated in semiconductor heterostructures, but these newly discovered superconductors are currently limited by their extremely large electronic disorder. Similarly, the electron mean free path in low-dimensional superconducting thin films is usually limited by interface scattering, in single-crystal or polycrystalline samples, or atomic-scale disorder, in amorphous materials, confining these examples to the extreme 'dirty limit'. Here we report the fabrication of a high-quality superconducting layer within a thin-film heterostructure based on SrTiO(3) (the first known superconducting semiconductor). By selectively doping a narrow region of SrTiO(3) with the electron-donor niobium, we form a superconductor that is two-dimensional, as probed by the anisotropy of the upper critical magnetic field. Unlike in previous examples, however, the electron mobility is high enough that the normal-state resistance exhibits Shubnikov-de Haas oscillations that scale with the perpendicular field, indicating two-dimensional states. These results suggest that delta-doped SrTiO(3) provides a model system in which to explore the quantum transport and interplay of both superconducting and normal electrons. They also demonstrate that high-quality complex oxide heterostructures can maintain electron coherence on the macroscopic scales probed by transport, as well as on the microscopic scales demonstrated previously.

Histologic, Clinical, and Radiologic Findings of Alveolar Bone Expansion and Osteomyelitis of the Jaws in Cats.

The objective of this study was to characterize clinical, radiologic, and histologic patterns of alveolar bone expansion and osteomyelitis in cats. Based on case materials submitted as surgical biopsy specimens, alveolar bone pathology was diagnosed in 28 cats. These cats had a total of 37 oral lesions with clinical and radiologic changes that involved bone and/or teeth, including periodontitis, bone expansion, tooth resorption, and/or chronic osteomyelitis; 32 lesions were evaluated by histopathology. Canine teeth were affected in 19 cats (27 affected teeth), with bilateral lesions in 5 (26.3%) cats. The caudal premolar and/or molar regions were affected in 10 cats (10 affected sites). All biopsy sites evaluated by a review of clinical images and/or radiographs had evidence of periodontitis. Clinical photographs showed expansion of alveolar bone in 13 of 16 (81%) biopsy sites evaluated. Radiologically, rarifying osseous proliferation of alveolar bone was seen at 26 of 27 (96%) biopsy sites, and tooth resorption occurred at 15 of 18 (83%) sites. Histologically, the tissue samples from canine sites had compressed trabeculae of mature remodeled bone, loose fibrous stroma with paucicellular inflammation, and mild proliferation of woven bone. Tissue samples from the premolar/molar biopsy sites were often highly cellular with mixed lymphoplasmacytic and chronic suppurative inflammation, ulceration with granulation tissue, and robust proliferation of woven bone. Alveolar bone expansion and osteomyelitis in cats occurs in conjunction with periodontal inflammation and frequently with tooth resorption.

Titanium dxy ferromagnetism at the LaAlO3/SrTiO3 interface.

A number of recent transport and magnetization studies have shown signs of ferromagnetism in the LaAlO3/SrTiO3 heterostructure, an unexpected property with no bulk analogue in the constituent materials. However, no experiment thus far has provided direct information on the host of the magnetism. Here we report spectroscopic investigations of the magnetism using element-specific techniques, including X-ray magnetic circular dichroism and X-ray absorption spectroscopy, along with corresponding model calculations. We find direct evidence for in-plane ferromagnetic order at the interface, with Ti(3+) character in the dxy orbital of the anisotropic t2g band. These findings establish a striking example of emergent phenomena at oxide interfaces.

Phytophagy impacts the quality and quantity of plant carbon resources acquired by mutualistic arbuscular mycorrhizal fungi.

Arbuscular mycorrhizal (AM) fungi associate with the roots of many plant species, enhancing their hosts access to soil nutrients whilst obtaining their carbon supply directly as photosynthates. AM fungi often face competition for plant carbon from other organisms. The mechanisms by which plants prioritise carbon allocation to mutualistic AM fungi over parasitic symbionts remain poorly understood. Here, we show that host potato plants (Solanum tuberosum cv. Désirée) selectively allocate carbon resources to tissues interacting with AM fungi rather than those interacting with phytophagous parasites (the nematode Globodera pallida). We found that plants reduce the supply of hexoses but maintain the flow of plant-derived fatty acids to AM fungi when concurrently interacting with parasites. Transcriptomic analysis suggest that plants prioritise carbon transfer to AM fungi by maintaining expression of fatty acid biosynthesis and transportation pathways, whilst decreasing the expression of mycorrhizal-induced hexose transporters. We also report similar findings from a different plant host species (Medicago truncatula) and phytophagous pest (the aphid Myzus persicae). These findings suggest a general mechanism of plant-driven resource allocation in scenarios involving multiple symbionts.

A review of mathematical models for the formation of vascular networks.

Two major mechanisms are involved in the formation of blood vasculature: vasculogenesis and angiogenesis. The former term describes the formation of a capillary-like network from either a dispersed or a monolayered population of endothelial cells, reproducible also in vitro by specific experimental assays. The latter term describes the sprouting of new vessels from an existing capillary or post-capillary venule. Similar mechanisms are also involved in the formation of the lymphatic system through a process generally called lymphangiogenesis. A number of mathematical approaches have been used to analyze these phenomena. In this paper, we review the different types of models, with special emphasis on their ability to reproduce different biological systems and to predict measurable quantities which describe the overall processes. Finally, we highlight the advantages specific to each of the different modelling approaches.