Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 374
Filter
1.
Schizophr Res ; 264: 549-556, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38335764

ABSTRACT

BACKGROUND: Help-seeking and treatment delays are increasingly critical areas of study in mental health services. The duration of untreated psychosis (DUP), or the time between illness onset and initiation of treatment, is a predictor of symptom remission and functioning for a first episode of psychosis (FEP). The World Health Organization recommends that specialized treatment for psychosis be initiated within the first three months of FEP onset. As a result, research has focused on factors that are associated with threshold-level DUP, while the experience of subthreshold psychotic symptoms (STPS) prior to a FEP may also complicate and present barriers to accessing care for young people. We therefore examine the possibility that STPS can impact DUP and its components. METHOD: Using a follow-back cross-sectional design, we sought to describe duration of untreated illness, length of prodrome, DUP, help-seeking delay, referral delay, and number of help-seeking contacts among FEP patients who did and did not have STPS prior to psychosis onset. RESULTS: We found that patients who experienced STPS had a longer median duration of untreated illness, prodrome length, DUP, and help-seeking delay compared to patients who did not have such symptoms. Referral delay did not differ substantially between the two groups. Importantly, treatment delays were extremely lengthy for many participants. CONCLUSIONS: Pre-onset STPS are associated with help-seeking delays along the pathway to care even during a FEP. Examining early signs and symptoms may help to improve and tailor interventions aimed at reducing treatment delays and ultimately providing timely care when the need arises.


Subject(s)
Mental Health Services , Psychotic Disorders , Humans , Adolescent , Treatment Delay , Cross-Sectional Studies , Psychotic Disorders/psychology , Time Factors
2.
Cell Rep ; 42(7): 112730, 2023 07 25.
Article in English | MEDLINE | ID: mdl-37453057

ABSTRACT

Cancer-associated mesothelial cells (CAMCs) in the tumor microenvironment are thought to promote growth and immune evasion. We find that, in mouse and human ovarian tumors, cancer cells express anti-Müllerian hormone (AMH) while CAMCs express its receptor AMHR2, suggesting a paracrine axis. Factors secreted by cancer cells induce AMHR2 expression during their reprogramming into CAMCs in mouse and human in vitro models. Overexpression of AMHR2 in the Met5a mesothelial cell line is sufficient to induce expression of immunosuppressive cytokines and growth factors that stimulate ovarian cancer cell growth in an AMH-dependent way. Finally, syngeneic cancer cells implanted in transgenic mice with Amhr2-/- CAMCs grow significantly slower than in wild-type hosts. The cytokine profile of Amhr2-/- tumor-bearing mice is altered and their tumors express less immune checkpoint markers programmed-cell-death 1 (PD1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4). Taken together, these data suggest that the AMH/AMHR2 axis plays a critical role in regulating the pro-tumoral function of CAMCs in ovarian cancer.


Subject(s)
Ovarian Neoplasms , Peptide Hormones , Female , Humans , Animals , Mice , Anti-Mullerian Hormone/genetics , Ovarian Neoplasms/genetics , Mice, Transgenic , Receptors, Transforming Growth Factor beta/metabolism , Tumor Microenvironment
4.
Nanoscale Adv ; 4(18): 3919-3927, 2022 Sep 13.
Article in English | MEDLINE | ID: mdl-36133330

ABSTRACT

In this study, molecular beam epitaxially grown axially configured ensemble GaAsSb/GaAs separate absorption, charge, and multiplication (SACM) region-based nanowire avalanche photodetector device on non-patterned Si substrate is presented. Our device exhibits a low breakdown voltage (V BR) of ∼ -10 ± 2.5 V under dark, photocurrent gain (M) varying from 20 in linear mode to avalanche gain of 700 at V BR at a 1.064 µm wavelength. Positive temperature dependence of breakdown voltage ∼ 12.6 mV K-1 further affirms avalanche breakdown as the gain mechanism in our SACM NW APDs. Capacitance-voltage (C-V) and temperature-dependent noise characteristics also validated punch-through voltage ascertained from I-V measurements, and avalanche being the dominant gain mechanism in the APDs. The ensemble SACM NW APD device demonstrated a broad spectral room temperature response with a cut-off wavelength of ∼1.2 µm with a responsivity of ∼0.17-0.38 A W-1 at -3 V. This work offers a potential pathway toward realizing tunable nanowire-based avalanche photodetectors compatible with traditional Si technology.

5.
Nucleic Acids Res ; 50(D1): D837-D847, 2022 01 07.
Article in English | MEDLINE | ID: mdl-34788826

ABSTRACT

Since 2005, the Pathogen-Host Interactions Database (PHI-base) has manually curated experimentally verified pathogenicity, virulence and effector genes from fungal, bacterial and protist pathogens, which infect animal, plant, fish, insect and/or fungal hosts. PHI-base (www.phi-base.org) is devoted to the identification and presentation of phenotype information on pathogenicity and effector genes and their host interactions. Specific gene alterations that did not alter the in host interaction phenotype are also presented. PHI-base is invaluable for comparative analyses and for the discovery of candidate targets in medically and agronomically important species for intervention. Version 4.12 (September 2021) contains 4387 references, and provides information on 8411 genes from 279 pathogens, tested on 228 hosts in 18, 190 interactions. This provides a 24% increase in gene content since Version 4.8 (September 2019). Bacterial and fungal pathogens represent the majority of the interaction data, with a 54:46 split of entries, whilst protists, protozoa, nematodes and insects represent 3.6% of entries. Host species consist of approximately 54% plants and 46% others of medical, veterinary and/or environmental importance. PHI-base data is disseminated to UniProtKB, FungiDB and Ensembl Genomes. PHI-base will migrate to a new gene-centric version (version 5.0) in early 2022. This major development is briefly described.


Subject(s)
Databases, Factual , Host-Pathogen Interactions/genetics , Phenotype , User-Computer Interface , Animals , Apicomplexa/classification , Apicomplexa/genetics , Apicomplexa/pathogenicity , Bacteria/classification , Bacteria/genetics , Bacteria/pathogenicity , Diplomonadida/classification , Diplomonadida/genetics , Diplomonadida/pathogenicity , Fungi/classification , Fungi/genetics , Fungi/pathogenicity , Insecta/classification , Insecta/genetics , Insecta/pathogenicity , Internet , Nematoda/classification , Nematoda/genetics , Nematoda/pathogenicity , Phylogeny , Plants/microbiology , Plants/parasitology , Virulence
6.
Ann R Coll Surg Engl ; 104(2): 125-129, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34730439

ABSTRACT

INTRODUCTION: In 2013, The Association of Coloproctology of Great Britain and Ireland (ACPGBI) issued a position statement regarding management of malignant polyps. We reviewed the management of endoscopically resected malignant colorectal polyps in a district general hospital to evaluate whether patients were being overtreated as per these guidelines. METHODS: All patients who underwent a complete, non-piecemeal endoscopic removal of a malignant polyp between October 2013 and September 2018 were studied. Polyps were risk stratified for residual disease and followed up as per the ACPGBI. Patients were divided into two groups based on management after polypectomy. Primary outcome measured was the presence of residual tumour or involved lymph nodes in the resection specimen. Secondary outcomes included complications and recurrence. RESULTS: Thirty-three patients were included: 21 in the non-operative group (NOG) and 12 in the operative group (OG). The ACPGBI risk score in the NOG varied between 1 and over 4 compared with the OG who all scored over 4. Two patients in the OG (16%) demonstrated residual disease. Five patients suffered a postoperative complication. No recurrences were noted in the OG and one in the NOG. CONCLUSION: Our findings against a backdrop of the available literature suggest that the risk of residual disease after malignant polypectomy may not be as high as stated by the ACPGBI. As a result, there is a risk of overtreating patients and exposing them to the significant complications of surgery if careful consideration is not exercised.


Subject(s)
Colonic Polyps , Colorectal Neoplasms , Colonic Polyps/pathology , Colonic Polyps/surgery , Colonoscopy/adverse effects , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Endoscopy , Humans , Retrospective Studies , Risk Factors , United Kingdom/epidemiology
7.
Ann Oncol ; 33(3): 288-298, 2022 03.
Article in English | MEDLINE | ID: mdl-34921960

ABSTRACT

BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. RESULTS: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. CONCLUSIONS: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.


Subject(s)
Ki-1 Antigen , Lymphoma, T-Cell, Peripheral , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Brentuximab Vedotin , Humans , Ki-1 Antigen/metabolism , Ki-1 Antigen/therapeutic use , Lymphoma, T-Cell, Peripheral/drug therapy , Vincristine/adverse effects
8.
Front Microbiol ; 12: 647565, 2021.
Article in English | MEDLINE | ID: mdl-34385981

ABSTRACT

BACKGROUND: Africa has one of the highest incidences of gonorrhea. Neisseria gonorrhoeae is gaining resistance to most of the available antibiotics, compromising treatment across the world. Whole-genome sequencing (WGS) is an efficient way of predicting AMR determinants and their spread in the population. Recent advances in next-generation sequencing technologies like Oxford Nanopore Technology (ONT) have helped in the generation of longer reads of DNA in a shorter duration with lower cost. Increasing accuracy of base-calling algorithms, high throughput, error-correction strategies, and ease of using the mobile sequencer MinION in remote areas lead to its adoption for routine microbial genome sequencing. To investigate whether MinION-only sequencing is sufficient for WGS and downstream analysis in resource-limited settings, we sequenced the genomes of 14 suspected N. gonorrhoeae isolates from Nairobi, Kenya. METHODS: Using WGS, the isolates were confirmed to be cases of N. gonorrhoeae (n = 9), and there were three co-occurrences of N. gonorrhoeae with Moraxella osloensis and N. meningitidis (n = 2). N. meningitidis has been implicated in sexually transmitted infections in recent years. The near-complete N. gonorrhoeae genomes (n = 10) were analyzed further for mutations/factors causing AMR using an in-house database of mutations curated from the literature. RESULTS: We observe that ciprofloxacin resistance is associated with multiple mutations in both gyrA and parC. Mutations conferring tetracycline (rpsJ) and sulfonamide (folP) resistance and plasmids encoding beta-lactamase were seen in all the strains, and tet(M)-containing plasmids were identified in nine strains. Phylogenetic analysis clustered the 10 isolates into clades containing previously sequenced genomes from Kenya and countries across the world. Based on homology modeling of AMR targets, we see that the mutations in GyrA and ParC disrupt the hydrogen bonding with quinolone drugs and mutations in FolP may affect interaction with the antibiotic. CONCLUSION: Here, we demonstrate the utility of mobile DNA sequencing technology in producing a consensus genome for sequence typing and detection of genetic determinants of AMR. The workflow followed in the study, including AMR mutation dataset creation and the genome identification, assembly, and analysis, can be used for any clinical isolate. Further studies are required to determine the utility of real-time sequencing in outbreak investigations, diagnosis, and management of infections, especially in resource-limited settings.

9.
Br J Oral Maxillofac Surg ; 59(10): 1157-1165, 2021 12.
Article in English | MEDLINE | ID: mdl-34281738

ABSTRACT

Due to the risk of occult cervical metastasis, elective neck dissection (END) is recommended in the management of patients with early oral cavity squamous cell carcinoma (OSCC) and a clinically node-negative (cN0) neck. This paper presents a systematic review and meta-analysis of studies that recorded isolated regional recurrence (RR) in the pathologically node-negative neck dissection (pN0) neck following END in order to quantify the failure rate. Pubmed and Ovid databases were systematically searched for relevant articles published between January 2009 and January 2019. Studies reporting RR following END in patients with OSCC who had no pathological evidence of lymph node metastasis were eligible for inclusion in this meta-analysis. In addition, a selection of large head and neck units were invited to submit unpublished data. Search criteria produced a list of 5448 papers, of which 18 studies met the inclusion criteria. Three institutions contributed unpublished data. This included a total of 4824 patients with median follow-up of 34 months (2.8 years). Eight datasets included patients staged T1-T4 with RR 17.3% (469/2711), 13 datasets included patients staged T1-T2 with RR 7.5% (158/2113). Overall across all 21 studies, isolated neck recurrence was identified in 627 cases giving a RR of 13.0% (627/4824) on meta-analysis. Understanding the therapeutic effectiveness of END provides context for evaluation of clinical management of the cN0 in these patients. A pathologically negative neck does not guarantee against future recurrence.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Neck Dissection , Neoplasm Staging , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck
10.
ESMO Open ; 6(4): 100172, 2021 08.
Article in English | MEDLINE | ID: mdl-34242968

ABSTRACT

BACKGROUND: More than 80% of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) patients harbor the (nucleophosmin) NPM1-ALK fusion gene t(2;5) chromosomal translocation. We evaluated the preclinical and clinical efficacy of ceritinib treatment of this aggressive lymphoma. MATERIALS AND METHODS: We studied the effects of ceritinib treatment in NPM1-ALK+ T-cell lymphoma cell lines in vitro and on tumor size and survival advantage in vivo utilizing tumor xenografts. We treated an NPM1-ALK+ ALCL patient with ceritinib. We reviewed all hematologic malignancies profiled by a large hybrid-capture next-generation sequencing (NGS)-based comprehensive genomic profiling assay for ALK alterations. RESULTS: In our in vitro experiments, ceritinib inhibited constitutive activation of the fusion kinase NPM1-ALK and downstream effector molecules STAT3, AKT, and ERK1/2, and induced apoptosis of these lymphoma cell lines. Cell cycle analysis following ceritinib treatment showed G0/G1 arrest with a concomitant decrease in the percentage of cells in S and G2/M phases. Further, treatment with ceritinib in the NPM1-ALK+ ALCL xenograft model resulted in tumor regression and improved survival. Of 19 272 patients with hematopoietic diseases sequenced, 58 patients (0.30%) harbored ALK fusions that include histiocytic disorders, multiple myeloma, B-cell neoplasms, Castleman's disease, and juvenile xanthogranuloma. A multiple relapsed NPM1-ALK+ ALCL patient treated with ceritinib achieved complete remission with ongoing clinical benefit to date, 5 years after initiation of therapy. CONCLUSIONS: This ceritinib translational study in NPM1-ALK+ ALCL provides a strong rationale for a prospective study of ceritinib in ALK+ T-cell lymphomas and other ALK+ hematologic malignancies.


Subject(s)
Lymphoma, Large-Cell, Anaplastic , Anaplastic Lymphoma Kinase/genetics , Humans , Lymphoma, Large-Cell, Anaplastic/drug therapy , Lymphoma, Large-Cell, Anaplastic/genetics , Nucleophosmin , Prospective Studies , Pyrimidines , Receptor Protein-Tyrosine Kinases/genetics , Sulfones
11.
Ann R Coll Surg Engl ; 103(7): e223-e226, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34192495

ABSTRACT

Hip disarticulation is the removal of the entire lower limb through the hip joint by detaching the femur from the acetabulum. This major ablative procedure is rarely performed for infection but may be required in severe necrotising fasciitis. We present a single centre retrospective review of all cases of emergency hip disarticulations in patients with necrotising fasciitis between 2010 and 2020. All five patients included in the review presented with acute lower limb pain and sepsis. Three patients had comorbidities predisposing them to necrotising fasciitis. Three were deemed to be high risk and two were at intermediate risk of developing necrotising fasciitis. There were two deaths in the postoperative period. Of the three survivors, two required revision surgery for a completion hindquarter amputation and one for flap closure. All three survivors had good functional outcomes after discharge from hospital. Despite its associated morbidity, emergency amputation of the entire lower limb is a life-saving treatment in cases of rapidly progressing necrotising fasciitis and should be considered as a first-line option in managing this condition.


Subject(s)
Disarticulation/methods , Emergency Treatment/methods , Fasciitis, Necrotizing/surgery , Hip Joint/surgery , Sepsis/prevention & control , Streptococcal Infections/surgery , Adult , Aged, 80 and over , Fasciitis, Necrotizing/complications , Fasciitis, Necrotizing/microbiology , Fasciitis, Necrotizing/mortality , Female , Hospital Mortality , Hospitals, District/statistics & numerical data , Hospitals, General/statistics & numerical data , Humans , Lower Extremity , Male , Retrospective Studies , Sepsis/microbiology , Severity of Illness Index , Streptococcal Infections/complications , Streptococcal Infections/microbiology , Streptococcal Infections/mortality , Streptococcus/isolation & purification , Treatment Outcome
12.
Int J Oral Maxillofac Surg ; 50(12): 1533-1539, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33714613

ABSTRACT

The evaluation of speech outcomes after resection and reconstruction of the oral tongue remains largely unsystematic. A cross-sectional study was performed to analyse the speech outcomes of patients who underwent curative treatment with appropriate reconstruction. Sixty-nine patients were assessed for speech intelligibility and phonetics using a validated speech intelligibility assessment tool in the local language. Volume defects were classified as class I (less than one third), II (one third to half), III (half to two-thirds), or IV (two-thirds to total glossectomy). Defect location was defined as lateral, tip, or sulcus. The χ2 test and Kruskal-Wallis test were used to test volume and location as predictors. Twenty-six patients had class I defects, 29 had class II defects, seven had class III defects, and seven had class IV defects. Twenty-two patients (31.9%) received adjuvant radiotherapy. Mean vowel, consonant, word, and paragraph intelligibility were 99.27%, 86.86%, 85.52%, and 88.72%, respectively. The incremental volume of the glossectomy defect was significantly correlated with speech intelligibility scores and phonatory alterations. In classes II and III, tip resection significantly affected interdental sounds. All patients in class III had affected alveolar and alveo-palatal sounds. The results positively corroborated the volume and location of the glossectomy defect to a classification system.


Subject(s)
Plastic Surgery Procedures , Tongue Neoplasms , Cross-Sectional Studies , Glossectomy , Humans , Speech Intelligibility , Tongue Neoplasms/surgery
13.
Soc Sci Med ; 272: 113719, 2021 03.
Article in English | MEDLINE | ID: mdl-33545496

ABSTRACT

OBJECTIVES: School racial/ethnic segregation in U.S. schoolsDifferences in school racial/ethnic composition may increase health disparities by concentrating educational opportunities that confer long-term health benefits in schools serving predominantly wwhite students. For racial minority students, high concentrations of white students may increase exposure to racismis also associated with psychologicstress, which may ultimately reduceing the long-term health benefits from educational opportunities. Meanwhile associations of racial/ethnic academic tacking within schools and health have been mixed. We sought to test whether: 1) differences in racial/ethnic composition between schools and, 2) racial/ethnic distribution of students in academic tracks within schools are associated with long-term health benefits or risks for white, Black and Latinx students. METHODS: We analyzed the National Longitudinal Study of Adolescent to Adult Health (12,438 participants, collected 1994-2008), to test whether the school-level segregation (percent of non-Latinx white students at participants' school during adolescence) was associated with adult health outcomes at ages 18-26 & 24-32, controlling for contextual factorscomparing Black, Latinx, and white students, and controlling for contextualf factors. A secondary analysis explored whether racial/ethnic cohorting across levels of English courses was associated with each health outcome. RESULTS: Attending a school with a higher percent of white students was associated with higher adult depression scores, substance abuse, and worse self-rated health for black Black students; lower depression scores, better self-rated health, and alcohol abuse for white students; and no health differences for Latinx students. Greater within school racial/ethnic cohorting across English courses was associated with increased odds of alcohol abuse for white students; decreased odds of alcohol abuse for Black and Latinx students; and decreased odds of drug abuse for Black students. CONCLUSION: Among Bblack youth, attending a school with a higher percentage of white students is associated with worse behavioral health in adulthood. Understanding the potential impacts of school racial/ethnic composition on health is critical to designing policies that maximize access to opportunity and health.Education policies should comprehensively address school quality and racism to maximize adult health.


Subject(s)
Ethnicity , Racial Groups , Adolescent , Adult , Black or African American , Humans , Longitudinal Studies , Schools , Young Adult
14.
Radiography (Lond) ; 27(2): 740-742, 2021 05.
Article in English | MEDLINE | ID: mdl-32943353

ABSTRACT

Gallstone ileus is a rare pathology, occurring in an estimated 0.5% of cases, which preferentially affect females and the elderly population. This rare pathology is the result of a fistulous connection between the bowel and gallbladder. This connection allows gallstones to pass into the bowel leading to mechanical obstruction. On rare occasions the enteric gallstone can act as a lead point causing intussusception. We present a rare case of intussusception secondary to gallstone ileus in a young, relatively asymptomatic patient. CT played a critical role in diagnosis and appropriate management of our patient.


Subject(s)
Gallstones , Ileus , Intestinal Obstruction , Intussusception , Aged , Female , Gallstones/complications , Gallstones/diagnostic imaging , Gallstones/surgery , Humans , Ileus/diagnostic imaging , Ileus/etiology , Ileus/surgery , Intussusception/diagnostic imaging , Intussusception/etiology , Intussusception/surgery
15.
Leukemia ; 35(3): 679-690, 2021 03.
Article in English | MEDLINE | ID: mdl-32606318

ABSTRACT

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes and is largely driven by the NOTCH/MYC pathway. Yet, additional oncogenic drivers are required for transformation. Here, we identify protein tyrosine phosphatase type 4 A3 (PRL3) as a collaborating oncogenic driver in T-ALL. PRL3 is expressed in a large fraction of primary human T-ALLs and is commonly co-amplified with MYC. PRL3 also synergized with MYC to initiate early-onset ALL in transgenic zebrafish and was required for human T-ALL growth and maintenance. Mass-spectrometry phosphoproteomic analysis and mechanistic studies uncovered that PRL3 suppresses downstream T-cell phosphorylation signaling pathways, including those modulated by VAV1, and subsequently suppresses apoptosis in leukemia cells. Taken together, our studies have identified new roles for PRL3 as a collaborating oncogenic driver in human T-ALL and suggest that therapeutic targeting of the PRL3 phosphatase will likely be a useful treatment strategy for T-ALL.


Subject(s)
Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/metabolism , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Protein Tyrosine Phosphatases/metabolism , T-Lymphocytes/pathology , Animals , Apoptosis , Biomarkers, Tumor/genetics , Cell Proliferation , Female , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Neoplasm Proteins/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Prognosis , Protein Tyrosine Phosphatases/genetics , T-Lymphocytes/metabolism , Tumor Cells, Cultured , Xenograft Model Antitumor Assays , Zebrafish
17.
Front Neurorobot ; 14: 15, 2020.
Article in English | MEDLINE | ID: mdl-32226372

ABSTRACT

Walking is one of the most relevant tasks that a person performs in their daily routine. Despite its mechanical complexities, any change in the external conditions that applies some external perturbation, or in the human musculoskeletal system that limits an individual's movement, entails a motor response that can either be compensatory or adaptive in nature. Incidentally, with aging or due to the occurrence of a neuro-musculoskeletal disorder, a combination of such changes including reduced sensory perception, muscle weakness, spasticity, etc. has been reported, and this can significantly degrade the human walking performance. Various studies in gait rehabilitation literature have identified a need for the development of better rehabilitation paradigms and have implied that an efficient human robot interaction is critical. Understanding how humans respond to a particular gait alteration can be beneficial in designing an effective rehabilitation paradigm. In this context, the current work investigates human locomotor adaptation to resistive alteration to the hip and ankle strategies of walking. A cable-driven robotic system, which does not add mobility constraints, was used to implement resistive force interventions within the hip and ankle joints separately through two experiments with eight healthy adult participants in each. In both cases, the intervention was applied during the push-off phase of walking, i.e., from pre-swing to terminal swing. The results showed that subjects in both groups adopted a compensatory response to the applied intervention and demonstrated intralimb and interlimb adaptation. Overall, the participants demonstrated a deviant gait implying lower limb musculoskeletal adjustments as if to compensate for a hip or ankle abnormality.

18.
Health Res Policy Syst ; 18(1): 29, 2020 Mar 04.
Article in English | MEDLINE | ID: mdl-32131848

ABSTRACT

BACKGROUND: Systems transformation for health promotion, involving engagement from multiple disciplines and levels of influence, requires an investment in partnership development. Integrated youth service is a collaborative model that brings organisations together to provide holistic care for youth. Frayme is an international knowledge translation network designed to support the uptake and scaling of integrated youth service. Social network analysis (SNA) is the study of relationships among social units and is useful to better understand how partners collaborate within a network to achieve major objectives. The purpose of this paper is to apply SNA to the Frayme network in order to (1) examine the level and strength of partnerships, (2) identify the strategies being employed to promote the main objectives and (3) apply the findings to current research in youth mental health and system transformation. METHODS: The PARTNER tool includes a validated survey and analysis software designed to examine partner interconnections. This tool was used to perform the SNA and 51 of the 75 partners completed the survey (14 researchers, 2 advisory groups and 35 organisations). A network map was created and descriptive frequencies were calculated. RESULTS: The overall network scores for the Frayme network were 20.6% for density, 81.5% for centralisation and 71.7% for overall trust. The Frayme secretariat received a 3.84 out of a possible 4 for value. In addition, the youth and family advisories each received a value score of 4 and all Leadership Team organisations received a score of 2.97 or above. CONCLUSIONS: The Frayme secretariat links many partners who would otherwise be disconnected and acts as a significant conduit for novel information. Frayme may have the opportunity to enhance value perceptions among broader network members by profiling individual organisations and the potential leveraging opportunities that might exist through their work. These findings increase understanding with respect to the mechanisms of network development and will be helpful to inform partnership development in the future. In addition, they contribute to the literature with respect to knowledge translation practice as well as the scaling of collaborative interventions within youth mental health.


Subject(s)
Adolescent Health Services/organization & administration , Health Promotion/organization & administration , International Agencies/organization & administration , International Cooperation , Mental Health Services/organization & administration , Social Networking , Translational Research, Biomedical/organization & administration , Adolescent , Child , Humans , Surveys and Questionnaires
19.
J Laryngol Otol ; 134(4): 350-353, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32172698

ABSTRACT

OBJECTIVES: Pharyngocutaneous fistulae are dreaded complications following total laryngectomy. This paper presents our experience using 3-5 ml gastrografin to detect pharyngeal leaks following total laryngectomy, and compares post-operative videofluoroscopy with clinical follow-up findings in the detection of pharyngocutaneous fistulae. METHODS: A retrospective case-control study was conducted of total laryngectomy patients. The control group (n = 85) was assessed clinically for development of pharyngocutaneous fistulae, while the study group (n = 52) underwent small-volume (3-5 ml) post-operative gastrografin videofluoroscopy. RESULTS: In the control group, 24 of 85 patients (28 per cent) developed pharyngocutaneous fistulae, with 6 requiring surgical correction. In the study group, 24 of 52 patients (46 per cent) had videofluoroscopy-detected pharyngeal leaks; 4 patients (8 per cent) developed pharyngocutaneous fistulae, but all cases resolved following non-surgical management. Patients who underwent videofluoroscopy had a significantly lower risk of developing pharyngocutaneous fistulae; sensitivity and specificity in the detection of pharyngocutaneous fistulae were 58 per cent and 100 per cent respectively. CONCLUSION: Small-volume gastrografin videofluoroscopy reliably identified small pharyngeal leaks. Routine use in total laryngectomy combined with withholding feeds in cases of early leaks may prevent the development of pharyngocutaneous fistulae.


Subject(s)
Cutaneous Fistula/diagnostic imaging , Diatrizoate Meglumine/administration & dosage , Fluoroscopy/methods , Laryngectomy/adverse effects , Pharyngeal Diseases/surgery , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cutaneous Fistula/prevention & control , Cutaneous Fistula/therapy , Female , Fluoroscopy/trends , Humans , Male , Mass Screening/instrumentation , Middle Aged , Pharynx/diagnostic imaging , Pharynx/pathology , Postoperative Complications/epidemiology , Retrospective Studies , Sensitivity and Specificity
20.
ANZ J Surg ; 89(5): E190-E194, 2019 05.
Article in English | MEDLINE | ID: mdl-30968539

ABSTRACT

BACKGROUND: Minimally invasive pancreaticoduodenectomy (PD) is a feasible option for periampullary tumours. However, it remains a complex procedure with no proven advantages over open PD (OPD). The aim of the study was to compare the outcomes between laparoscopic-assisted PD (LAPD) and OPD using a propensity score-matched analysis. METHODS: Retrospective review of 40 patients who underwent PD for periampullary tumours between January 2014 and December 2016 was conducted. The patients were matched 1:1 for age, gender, body mass index, Charlson comorbidty index, tumour size and haematological indices. Peri-operative outcomes were evaluated. RESULTS: LAPD appeared to have a longer median operative time as compared to OPD (LAPD, 425 min (285-597) versus OPD, 369 min (260-500)) (P = 0.066). Intra-operative blood loss was comparable between both groups. Respiratory complications were five times higher in the OPD group (LAPD, 5% versus OPD, 25%) (P = 0.077), while LAPD patients required less time to start ambulating post-operatively (LAPD, 2 days versus OPD, 2 days) (P = 0.021). Pancreas-specific complications and morbidity/mortality rates were similar. CONCLUSION: LAPD is a safe alternative to OPD in a select group of patients for an institution starting out with minimally invasive PD, and can be used to bridge the learning curve required for total laparoscopic PD.


Subject(s)
Laparoscopy/methods , Laparotomy/methods , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/methods , Adult , Aged , Blood Loss, Surgical , Cohort Studies , Female , Humans , Laparoscopy/adverse effects , Laparotomy/adverse effects , Male , Middle Aged , Operative Time , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreaticoduodenectomy/adverse effects , Patient Selection , Postoperative Complications/epidemiology , Postoperative Complications/physiopathology , Propensity Score , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...