Publications by authors named "Philip John"

154 Publications

The road to tranquil equanimity: excerpts from the Bhagavad Gita - psychiatry in sacred texts.

Br J Psychiatry 2021 Mar;218(3):130

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http://dx.doi.org/10.1192/bjp.2020.214DOI Listing
March 2021

Binary blended fly ash concrete with improved chemical resistance in natural and industrial environments.

Environ Sci Pollut Res Int 2021 Feb 2. Epub 2021 Feb 2.

Corrosion Science and Technology Division, MCG, Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, HBNI, Kalpakkam, Tamil Nadu, 603102, India.

This study reports the enhanced chemical resistance of a blended concrete mix (CFNI) made with 40 wt.% fly ash, 2 wt.% nanoparticles, and 2 wt.% sodium nitrite inhibitor as partial replacement of cement against calcium leaching, acid and sulfate attacks. The concrete test specimens of four different compositions were fabricated and immersed in natural seawater, 3% sulfuric acid solution, and 10% magnesium sulfate solution for 120 days. Long-term chemical deterioration of the concrete systems is evaluated by assessing visual changes of the specimens and solutions along with the changes in percentage mass loss, compressive strength of the concrete, pH of the solution, and dimensions. The results indicate that CFNI concrete exhibits a superior resistance against chemical attack under all the three aggressive environments. Detailed chemical characterization of the specimens, carried out using XRD, FTIR, and thermogravimetric analysis, reveal a reduced CaO content, absence of deterioration phases like ettringite, brucite, and enhanced C-S-H content in the CFNI concrete. The addition of nanoparticles and inhibitors into fly ash concrete has lowered w/c ratio, increased surface pH, enabled conversion of soluble calcium hydroxide into insoluble calcium silicate hydrate, filled pores/voids, and reduced shrinkage and cracking. The compact microstructure of the CFNI prevented leaching and reduced the ingress of aggressive chemical ions into the concrete. Our results demonstrate that incorporation of nanoparticles and inhibitor into the fly ash concrete composition is ideally suited for the design of high-quality, low-permeable concrete structures that is the key for enhanced chemical resistance in natural and industrial environments.
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http://dx.doi.org/10.1007/s11356-021-12453-4DOI Listing
February 2021

Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis.

Nat Commun 2021 01 12;12(1):338. Epub 2021 Jan 12.

Computational Oncology Service, Department of Epidemiology & Biostatistics, Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.

Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. Here we leverage peripheral blood sequencing data from 32,442 cancer patients to jointly characterize gene mutations (n = 14,789) and mCAs (n = 383) in CH. Recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal alterations, indicating that these selection mechanisms are operative early in clonal evolution. CH with composite genotypes defines a patient group at high risk of leukemia progression (3-year cumulative incidence 14.6%, CI: 7-22%). Multivariable analysis identifies mCA as an independent risk factor for leukemia development (HR = 14, 95% CI: 6-33, P < 0.001). Our results suggest that mCA should be considered in conjunction with gene mutations in the surveillance of patients at risk of hematologic neoplasms.
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http://dx.doi.org/10.1038/s41467-020-20565-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804935PMC
January 2021

Infrared thermal imaging based study of localized cold stress induced thermoregulation in lower limbs: The role of age on the inversion time.

J Therm Biol 2020 Dec 14;94:102781. Epub 2020 Nov 14.

Smart Materials Section, Corrosion Science and Technology Division, Materials Characterization Group, Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, HBNI, Kalpakkam, Tamil Nadu, PIN 603102, India.

Thermoregulatory control of human body temperature is of paramount importance for normal bodily functions. Exposure of the upper and lower limbs to localized cold stress can cause cold-induced injuries and often lower limbs are more susceptible to damages from cold-induced injuries. In this study, we use infrared thermal imaging to probe localized cold stress induced cutaneous vasoconstriction of lower limbs in 33 healthy subjects. The cold stress is actuated by applying ice to the plantar surfaces of the lower limbs for 180 s and after removal of the cold stress, infrared thermography is utilized to non-invasively monitor the time-dependent variations in vein pixel temperatures on the dorsal surfaces of the stimulated and non-stimulated feet. It is observed that the vein pixel temperature of the stimulated foot showed a non-monotonic variation with time, consisting of an initial decrease and the presence of an inversion time, beyond which temperature is regained. The initial decrease in vein pixel temperature of the stimulated foot is attributed to the reduced blood flow caused by the cold stress induced severe vasoconstriction. Beyond the inversion time, the vein pixel temperature is found to increase due to rewarming of the surrounding skin. Experimental findings indicate that the inversion time linearly increased with the age of the subject, indicating a reduced thermoregulatory efficiency for the aged subjects. This study provides a thermal imaging-based insight into the skin temperature re-distribution during the early stages of blood perfusion in lower limbs, after an exposure to a localized acute cold stress. Statistical analyses reveal that subject height, weight, body-mass index and gender do not influence the inversion time significantly. The experimental findings are important towards rapid evaluation of personnel fitness for deployment in extreme cold environment, treatment of cold-induced injuries and probing of thermoregulatory impairments.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102781DOI Listing
December 2020

Cancer therapy shapes the fitness landscape of clonal hematopoiesis.

Nat Genet 2020 11 26;52(11):1219-1226. Epub 2020 Oct 26.

Computational Oncology Service, Department of Epidemiology & Biostatistics, Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Acquired mutations are pervasive across normal tissues. However, understanding of the processes that drive transformation of certain clones to cancer is limited. Here we study this phenomenon in the context of clonal hematopoiesis (CH) and the development of therapy-related myeloid neoplasms (tMNs). We find that mutations are selected differentially based on exposures. Mutations in ASXL1 are enriched in current or former smokers, whereas cancer therapy with radiation, platinum and topoisomerase II inhibitors preferentially selects for mutations in DNA damage response genes (TP53, PPM1D, CHEK2). Sequential sampling provides definitive evidence that DNA damage response clones outcompete other clones when exposed to certain therapies. Among cases in which CH was previously detected, the CH mutation was present at tMN diagnosis. We identify the molecular characteristics of CH that increase risk of tMN. The increasing implementation of clinical sequencing at diagnosis provides an opportunity to identify patients at risk of tMN for prevention strategies.
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http://dx.doi.org/10.1038/s41588-020-00710-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891089PMC
November 2020

Polydimethylsiloxane-graphene oxide nanocomposite coatings with improved anti-corrosion and anti-biofouling properties.

Environ Sci Pollut Res Int 2021 Feb 8;28(6):7404-7422. Epub 2020 Oct 8.

Corrosion Science and Technology Division, Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam, 603102, India.

We demonstrate enhanced anti-corrosion and anti-biofouling properties of graphene oxide-silica-polydimethylsiloxane (GSP) coating on carbon steel (CS). Electrochemical analyses of GSP-coated carbon steel exposed to Gram-positive Bacillus sp., Gram-negative Pseudomonas sp., and freshwater bacterial cultures for 72 h showed a 3-5 orders of magnitude reduction in i values and high impedance values (10 Ω) as compared with polished specimens. The corrosion protection efficiency of GSP-coated specimens was 99.9% against Bacillus sp. and freshwater culture and it was 89.6% against Pseudomonas sp. Evaluation of anti-biofouling property of GSP coating using microbiological and epifluorescence microscopic techniques showed three order reductions in total viable cells on GSP-coated specimens exposed to bacterial cultures. Confocal laser scanning microscopic analysis of biofilm architecture confirmed a significant reduction of biomass and biofilm thickness on GSP-coated CS demonstrating an excellent anti-biofouling activity of GSP.
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http://dx.doi.org/10.1007/s11356-020-11068-5DOI Listing
February 2021

Rare broncho-pulmonary arterial fistula in a healthy 9-year-old girl.

BMJ Case Rep 2020 Oct 1;13(10). Epub 2020 Oct 1.

Pediatric Respirology, Hospital for Sick Children, Toronto, Ontario, Canada.

A 9-year-old previously well girl presented with multiple episodes of large volume haemoptysis and right sided consolidation. She continued to have haemoptysis despite intravenous antibiotics. CT chest suggested a right mainstem endobronchial lesion; this was not seen on bronchoscopy where an extensive blood clot was removed. Distal flexible bronchoscopy could not identify the source of bleeding. CT angiogram revealed a broncho-pulmonary arterial fistula, a rare cause of haemoptysis in children. Endovascular embolisation resulted in short-term symptom resolution; however, haemoptysis recurred months later, leading to re-embolisation. This case highlights a stepwise approach to the workup of large volume haemoptysis.
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http://dx.doi.org/10.1136/bcr-2020-234865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534672PMC
October 2020

Chemotherapy and COVID-19 Outcomes in Patients With Cancer.

J Clin Oncol 2020 10 14;38(30):3538-3546. Epub 2020 Aug 14.

Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: Coronavirus-2019 (COVID-19) mortality is higher in patients with cancer than in the general population, yet the cancer-associated risk factors for COVID-19 adverse outcomes are not fully characterized.

Patients And Methods: We reviewed clinical characteristics and outcomes from patients with cancer and concurrent COVID-19 at Memorial Sloan Kettering Cancer Center until March 31, 2020 (n = 309), and observed clinical end points until April 13, 2020. We hypothesized that cytotoxic chemotherapy administered within 35 days of a COVID-19 diagnosis is associated with an increased hazard ratio (HR) of severe or critical COVID-19. In secondary analyses, we estimated associations between specific clinical and laboratory variables and the incidence of a severe or critical COVID-19 event.

Results: Cytotoxic chemotherapy administration was not significantly associated with a severe or critical COVID-19 event (HR, 1.10; 95% CI, 0.73 to 1.60). Hematologic malignancy was associated with increased COVID-19 severity (HR, 1.90; 95% CI, 1.30 to 2.80). Patients with lung cancer also demonstrated higher rates of severe or critical COVID-19 events (HR, 2.0; 95% CI, 1.20 to 3.30). Lymphopenia at COVID-19 diagnosis was associated with higher rates of severe or critical illness (HR, 2.10; 95% CI, 1.50 to 3.10). Patients with baseline neutropenia 14-90 days before COVID-19 diagnosis had worse outcomes (HR, 4.20; 95% CI, 1.70 to 11.00). Findings from these analyses remained consistent in a multivariable model and in multiple sensitivity analyses. The rate of adverse events was lower in a time-matched population of patients with cancer without COVID-19.

Conclusion: Recent cytotoxic chemotherapy treatment was not associated with adverse COVID-19 outcomes. Patients with active hematologic or lung malignancies, peri-COVID-19 lymphopenia, or baseline neutropenia had worse COVID-19 outcomes. Interactions among antineoplastic therapy, cancer type, and COVID-19 are complex and warrant further investigation.
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http://dx.doi.org/10.1200/JCO.20.01307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571792PMC
October 2020

Efficacy of imidazolium and piperidinium based ionic liquids on inhibiting biofilm formation on titanium and carbon steel surfaces.

Anal Chim Acta 2020 Aug 21;1126:38-51. Epub 2020 Jun 21.

Corrosion Science and Technology Division, Metallurgy and Materials Group Indira Gandhi Centre for Atomic Research, Kalpakkam, 603102, India; Homi Bhabha National Institute, Kalpakkam, 603102, India.

In the present study, the efficacies of three different cationic and anionic ionic liquids (ILs) on biofilm formation on materials used in cooling water systems were evaluated. Two imidazolium based ILs; 1-Ethyl 3-Methylimidazolium tetrafluoroborate - (IL-E) and 1-Butyl-3-methylimidazolium chloride - (IL-I) with anionic fluoride and chloride groups and one piperidinium based IL, N-methyl-N-propylpiperidinium bis(trifluoromethylsulfonyl)imide - (IL-M) with fluoromethyl group as anion were used. The efficacy of these ILs were evaluated on planktonic and sessile cells of major biofilm formers in cooling water systems using Gram negative bacterium Pseudomonas sp. and Gram positive bacterium Bacillus sp. Further their effect on inhibiting biofilm formation on titanium and carbon steel surfaces were also evaluated. Results showed that planktonic cells of Pseudomonas sp. and Bacillus sp. were effectively inhibited by 25 ppm of IL-M and IL-E, respectively. For both bacteria, 50 ppm of IL-I was enough to inhibit and eradicate the sessile cell formation. Among the three ILs, IL-E was the best in inhibiting the adhesion of bacterial cells on Ti and CS surfaces. These results suggest that Imidazolium based ILs are effective in controlling sessile cell formation and eradicating mature biofilm as compared to piperidinium based IL. Further, Imidazolium based IL with fluoride anion (IL-E) was the best in inhibiting adhesion of these bacterial cells and thereby biofilm formation on material surfaces. This study establishes the feasibility of using ILs in cooling water system for bacterial biofilm control along with other conventional biofouling control methods.
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http://dx.doi.org/10.1016/j.aca.2020.05.072DOI Listing
August 2020

Outils de dépistage pour l’évaluation virtuelle de la cognition.

Can Fam Physician 2020 07;66(7):e185-e186

Spécialiste en médecine gériatrique à Ottawa (Ontario).

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365164PMC
July 2020

Screening tools for virtual assessment of cognition.

Can Fam Physician 2020 07;66(7):502-503

Geriatric specialist in Ottawa, Ont.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365161PMC
July 2020

Observation of soft glassy behavior in a magnetic colloid exposed to an external magnetic field.

Soft Matter 2020 Aug 14;16(30):7126-7136. Epub 2020 Jul 14.

Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, HBNI, Kalpakkam 603 102, India.

We provide the first experimental evidence for soft glassy behavior in a sterically stabilized magnetic colloid (ferrofluid) of relatively low volume fraction (φ = 0.037) when a uniform magnetic field is applied at a sufficiently high rate (fast quench). Fast magnetic-field quenches favor structural arrest of field-induced aggregates, owing to insufficient time to settle into lower energy states, thereby pushing the system to a frustrated metastable configuration like a repulsive glass. Brownian dynamics simulations are used to show that the polydisperse ferrofluid (as in experiments) forms thick ropes aligned along the field direction, while a monodisperse ferrofluid does not. The simulations show that there is practically no ordering of the thin, monodisperse chains, while the thick, polydisperse ropes show positional ordering with a typical center-center separation between the particles in different ropes of about 0.39 μm. As a consequence of structural arrest, the ferrofluid exhibits aging with broken time-translational invariance, a hallmark of glassy dynamics. The superposition of strain and creep compliance curves obtained from rheological measurements at different waiting times in the effective time domain corroborates the soft glassy behavior when exposed to a magnetic field applied at a fast ramp rate.
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http://dx.doi.org/10.1039/d0sm00830cDOI Listing
August 2020

Enhanced magnetic heating efficiency at acidic pH for magnetic nanoemulsions stabilized with a weak polyelectrolyte.

J Colloid Interface Sci 2020 Nov 27;579:582-597. Epub 2020 Jun 27.

Smart Materials Section, Corrosion Science and Technology Division, Materials Characterization Group, Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, HBNI, Kalpakkam, Tamil Nadu 603102, India. Electronic address:

Hypothesis: Magnetic fluid hyperthermia has attracted considerable attention for cancer therapeutics. Magnetic nanoemulsions are potential candidates for multi-modal hyperthermia due to the possibility of volumetric loading with suitable chemo/photo-therapy agents. Often, the nanocarriers are stabilized using organic molecules that behave differently under varying pH and hence, an understanding of their interfacial behaviour is important for practical applications.

Experiments: We probe the magnetic heating efficiency of poly acrylic acid (PAA) stabilized oil-in-water magnetic nanoemulsions, as a function of pH, where the conformational changes of the PAA molecules are studied using dynamic light scattering and inter-droplet force measurements.

Findings: A ~50% enhanced heating efficiency is observed when solution pH is reduced from ~9 to 3, which is attributed to the coil-to-globule conformational changes of the PAA molecules. The increased ionization of the carboxylic acid groups, at higher pH, leads to reduced hydrophobicity that results in an increase in the interfacial thermal resistance causing a lower magneto-thermal heating efficiency at higher pH. The proposed interfacial heat transfer hypothesis is experimentally verified using thermal imaging, where a lower rate of heat transfer is obtained at higher pH. The observed enhanced hyperthermia efficiency at low pH is beneficial for designing efficient pH-responsive nano-carriers for multi-modal hyperthermia.
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http://dx.doi.org/10.1016/j.jcis.2020.06.093DOI Listing
November 2020

Validation of a digital pathology system including remote review during the COVID-19 pandemic.

Mod Pathol 2020 11 22;33(11):2115-2127. Epub 2020 Jun 22.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

Remote digital pathology allows healthcare systems to maintain pathology operations during public health emergencies. Existing Clinical Laboratory Improvement Amendments regulations require pathologists to electronically verify patient reports from a certified facility. During the 2019 pandemic of COVID-19 disease, caused by the SAR-CoV-2 virus, this requirement potentially exposes pathologists, their colleagues, and household members to the risk of becoming infected. Relaxation of government enforcement of this regulation allows pathologists to review and report pathology specimens from a remote, non-CLIA certified facility. The availability of digital pathology systems can facilitate remote microscopic diagnosis, although formal comprehensive (case-based) validation of remote digital diagnosis has not been reported. All glass slides representing routine clinical signout workload in surgical pathology subspecialties at Memorial Sloan Kettering Cancer Center were scanned on an Aperio GT450 at ×40 equivalent resolution (0.26 µm/pixel). Twelve pathologists from nine surgical pathology subspecialties remotely reviewed and reported complete pathology cases using a digital pathology system from a non-CLIA certified facility through a secure connection. Whole slide images were integrated to and launched within the laboratory information system to a custom vendor-agnostic, whole slide image viewer. Remote signouts utilized consumer-grade computers and monitors (monitor size, 13.3-42 in.; resolution, 1280 × 800-3840 × 2160 pixels) connecting to an institution clinical workstation via secure virtual private network. Pathologists subsequently reviewed all corresponding glass slides using a light microscope within the CLIA-certified department. Intraobserver concordance metrics included reporting elements of top-line diagnosis, margin status, lymphovascular and/or perineural invasion, pathology stage, and ancillary testing. The median whole slide image file size was 1.3 GB; scan time/slide averaged 90 s; and scanned tissue area averaged 612 mm. Signout sessions included a total of 108 cases, comprised of 254 individual parts and 1196 slides. Major diagnostic equivalency was 100% between digital and glass slide diagnoses; and overall concordance was 98.8% (251/254). This study reports validation of primary diagnostic review and reporting of complete pathology cases from a remote site during a public health emergency. Our experience shows high (100%) intraobserver digital to glass slide major diagnostic concordance when reporting from a remote site. This randomized, prospective study successfully validated remote use of a digital pathology system including operational feasibility supporting remote review and reporting of pathology specimens, and evaluation of remote access performance and usability for remote signout.
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http://dx.doi.org/10.1038/s41379-020-0601-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306935PMC
November 2020

Use of Tissue Plasminogen Activator in Abdominal Abscesses in Children-A Single-Center Randomized Control Trial.

Can Assoc Radiol J 2020 Apr 13:846537120914263. Epub 2020 Apr 13.

Image Guided Therapy, Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada.

Purpose: To establish the efficacy of once-per-day intracavitary tissue plasminogen activator (tPA) in the treatment of pediatric intra-abdominal abscesses.

Methods: A single-center prospective, double-blinded, randomized controlled trial of the use of intracavitary tPA in abdominal abscesses in children. Patients were randomized to either tPA-treatment or saline-treatment groups. Primary outcome was drainage catheter dwell (hours). Secondary outcomes were length of hospital stay, times to discharge, clinical and sonographic resolution, and adverse events (AEs).

Results: Twenty-eight children were randomized to either group (n = 14 each). Demographics between groups were not significantly different (age = .28; weight = .40; gender = .44). There were significantly more abscesses in the tPA-treated group ( = .03). Abscesses were secondary to perforated appendicitis (n = 25) or postappendectomy (n = 3). Thirty-four abscesses were drained, 4 aspirated, 3 neither drained/aspirated. There was no significant difference in number of drains ( = .14), drain size ( = .19), primary outcome ( = .077), or secondary outcomes found. No procedural or intervention drug-related AEs occurred. No patient in the saline-treated group required to be switched/treated with tPA.

Conclusion: No significant difference in the length of catheter dwell time, procedure time to discharge, or time to resolution was found. Intracavitary tPA was not associated with morbidity or mortality. The results neither support nor negate routine use of tPA in the drainage of intra-abdominal abscess in children. It is possible that a multicentre study with a larger number of patients may answer this question more definitively.
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http://dx.doi.org/10.1177/0846537120914263DOI Listing
April 2020

Comparison of therapy-related and de novo core binding factor acute myeloid leukemia: A bone marrow pathology group study.

Am J Hematol 2020 07 20;95(7):799-808. Epub 2020 Apr 20.

Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.

This multi-institutional study retrospectively evaluated clinicopathologic and genetic characteristics in 351 patients with core-binding-factor acute myeloid leukemia (CBF-AML), comprising 69 therapy-related (t-CBF-AML) and 282 de novo cases. The T-CBF-AML patients were older, had lower WBC counts, and slightly higher hemoglobin than patients with de novo disease. Secondary cytogenetic abnormalities were more frequent in patients with de novo disease than t-CBF-AML (57.1% vs 41.1%, P = .026). Patients with secondary cytogenetic abnormalities had longer overall survival (OS) than those without abnormalities (median 190 vs 87 months, P = .021); trisomy 8, trisomy 22, and loss of the X or Y chromosome were associated with longer OS. In the 165 cases performed of targeted gene sequencing, pathogenic mutations were detected in 75.7% of cases, and were more frequent in de novo than in therapy-related disease (P = .013). Mutations were found in N/KRAS (37.0%), FLT3 (27.8%), KIT (17.2%), TET2 (4.9%), and ASXL1 (3.9%). The TET2 mutations were associated with shorter OS (P = .012) while N/KRAS mutation was associated with longer OS in t(8;21) AML patients (P = .001). The KIT mutation did not show prognostic significance in this cohort. Although they received similar therapy, t-CBF-AML patients had shorter OS than de novo patients (median 69 vs 190 months, P = .038). In multivariate analysis of all patients, older age and absence of any secondary cytogenetic abnormalities were significant predictors of shorter OS. Among the t-CBF-AML subset, age and hemoglobin were significant on multivariate analysis. This study demonstrated that although de novo and t-CBF-AML patients share many features, t-CBF-AML patients have worse clinical outcome than de novo patients.
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http://dx.doi.org/10.1002/ajh.25814DOI Listing
July 2020

Is Routine Preprocedural Bloodwork Needed for Elective Central Venous Access Device Removals in Children without Bleeding Dyscrasias?

J Vasc Interv Radiol 2020 Feb 26;31(2):276-281.e1. Epub 2019 Dec 26.

Division of Image Guided Therapy, Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada.

Purpose: To assess the utility of routine preprocedural bloodwork during elective removal of central venous access devices (CVADs) with respect to bleeding complications.

Materials And Methods: Patients who underwent removal of a CVAD (tunneled central venous catheter [CVC] or port) by the interventional radiology service between January 2009 and December 2013 were retrospectively reviewed. Removals for infection or malfunction, without preprocedural bloodwork, with another concurrent procedure at the time of CVAD removal, or in patients with a bleeding dyscrasia were excluded. Peripherally inserted central catheter removals and temporary CVAD removals were also excluded. Routine preprocedural bloodwork included hemoglobin, platelet count, partial thromboplastin time, and International Normalized Ratio. Postprocedural complications were classified according to the Society of Interventional Radiology clinical practice guidelines.

Results: There were 802 CVAD removals in 777 patients (351 female, 426 male). Average patient age was 8.6 years (range, 5 wk to 19 y). In total, 246 permanent CVCs and 556 ports were removed. A total of 802 cases had preprocedural bloodwork. Of the 49 patients who had a bleeding complication after the procedure (6.1%; 49 of 802), 44 had normal findings on preprocedural bloodwork and 5 had abnormal findings. There was no statistically significant difference in bleeding complications between those with normal and abnormal bloodwork results (P = .7740).

Conclusions: Routine bloodwork is not necessary before elective CVAD removal in children without a bleeding dyscrasia. Most children have normal findings on preprocedural bloodwork, and the incidence of postprocedural bleeding is low and not determined by bloodwork results.
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http://dx.doi.org/10.1016/j.jvir.2019.10.012DOI Listing
February 2020

Empowerment of Workers in Oral Health Care: A Kerala Experience.

Int J Clin Pediatr Dent 2019 Jul-Aug;12(4):268-272

Department of Pedodontics, Pushpagiri College of Dental Sciences, Thiruvalla, Kerala, India.

Introduction: Oral diseases are a serious public health problem, which affects the overall health of a person. The lack of available and affordable oral health services, especially in a developing country like India, not only results in aggravation of the disease, but also enhances the cost of treatment and care. Education and involvement of community workers like workers aid to remove stigma, discrimination and provide better atmosphere conducive for patients with various diseases.

Aim: To assess the knowledge and practice of oral health care among the AWWs of the Pulikeezh block Panchayath before and after an oral health education training.

Materials And Methods: A self-administered questionnaire was distributed to workers of the Pulikeezh block Panchayath, Thiruvalla, Kerala before and after an oral health education training within a period of 3 months.

Result: The mean knowledge and practice scores in the pretest were found to be 9.6 + 2.2 and 5.0 + 1.0 respectively. The posttest conducted after a 3-month period showed an increase in the knowledge and practice score with a mean of 10.9 + 2.2 and 5.7 + 0.6 respectively. The increase in knowledge and practice was statistically significant ( < 0.0001).

Conclusion: Empowered women are recognizably key agents in the change process who can play an effective role for health promotion. AWWs can function as oral health guides who can create awareness and help in prevention oral diseases.

Clinical Significance: As the oral health of an individual is set in the preschool period and more than 90% of dental diseases are preventable; preventive factors established around this age will determine the person's dental health for many years to come. The inclusion of oral health education in centers can be helpful in prevention of dental diseases.

How To Cite This Article: Cherian SA, Joseph E, Empowerment of Workers in Oral Health Care: A Kerala Experience. Int J Clin Pediatr Dent 2019;12(4):268-272.
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http://dx.doi.org/10.5005/jp-journals-10005-1636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898873PMC
December 2019

Klippel-Trenaunay Syndrome.

Authors:
Philip R John

Tech Vasc Interv Radiol 2019 Dec 23;22(4):100634. Epub 2019 Sep 23.

Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Canada. Electronic address:

Klippel-Trenaunay syndrome or KTS is a complex vascular syndrome associated with overgrowth occurring as a result of somatic mutations in the PIK3CA gene. Patients are diagnosed on the basis of physical findings, sometimes with supportive imaging, of commonly a segmental anomaly with a cutaneous port-wine stain, lymphatic and venous malformations and overgrowth. The severity of the component vascular malformations and the degree of overgrowth varies from patient to patient which demands care given by a multi-professional team with regular follow-up in a specialist clinic. Some patients may present with acute life-threatening problems, often as a result of veno-thromboembolic events (VTEs) especially following surgical and invasive radiological procedures. Awareness of such problems is vital and prophylactic measures to reduce such risks are paramount. The interventional radiologist is vital to the care team as he/she can undertake procedures including endovascular closure of significant venous anomalies which predispose to such VTEs. Although these procedures can be lengthy and complex, they can now provide a minimally invasive means to reduce the risk from life-threatening and sometimes fatal VTEs. The results however from such interventions will require long-term studies which to date are unavailable.
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http://dx.doi.org/10.1016/j.tvir.2019.100634DOI Listing
December 2019

A Small-Molecule Pan-Id Antagonist Inhibits Pathologic Ocular Neovascularization.

Cell Rep 2019 10;29(1):62-75.e7

Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Id helix-loop-helix (HLH) proteins (Id1-4) bind E protein bHLH transcription factors, preventing them from forming active transcription complexes that drive changes in cell states. Id proteins are primarily expressed during development to inhibit differentiation, but they become re-expressed in adult tissues in diseases of the vasculature and cancer. We show that the genetic loss of Id1/Id3 reduces ocular neovascularization in mouse models of wet age-related macular degeneration (AMD) and retinopathy of prematurity (ROP). An in silico screen identifies AGX51, a small-molecule Id antagonist. AGX51 inhibits the Id1-E47 interaction, leading to ubiquitin-mediated degradation of Ids, cell growth arrest, and reduced viability. AGX51 is well-tolerated in mice and phenocopies the genetic loss of Id expression in AMD and ROP models by inhibiting retinal neovascularization. Thus, AGX51 is a first-in-class compound that antagonizes an interaction formerly considered undruggable and that may have utility in the management of multiple diseases.
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http://dx.doi.org/10.1016/j.celrep.2019.08.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896334PMC
October 2019

Template-Free One-Step Electrodeposition Method for Fabrication of Robust Superhydrophobic Coating on Ferritic Steel with Self-Cleaning Ability and Superior Corrosion Resistance.

Langmuir 2019 Oct 16;35(39):12665-12679. Epub 2019 Sep 16.

Corrosion Science and Technology Division, Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Homi Bhabha National Institute , Indira Gandhi Centre for Atomic Research , Kalpakkam - 603 102 , India.

The corrosion of ferritic steel, a widely used structural material in the power and nuclear industries exposed to humid coastal environments, is a major concern. Here, we present a template-free one-step electrodeposition method for the fabrication of a robust superhydrophobic (SHP) coating on ferritic steel with excellent mechanical stability, enhanced corrosion resistance, and self-cleaning ability. By varying the electrodeposition time and potential, the micronanoscale hierarchical surface structures were optimized. The coated SHP surfaces were characterized by water contact angle measurement, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The coated surfaces showed a characteristic cauliflower morphology of cerium myristate with micronanoscale features. The maximum water contact angle achieved was 162.8 ± 2.4°. Shear abrasion testing showed good mechanical durability for the prepared coatings. The as-prepared SHP coating showed a five order reduction in corrosion current density (4.14 × 10 A/cm) and corrosion rate (4.63 × 10 mm/y) as compared to the bare sample. Further, a six order enhancement in the polarization resistance (1.55 × 10 Ω) was also observed in agressive chloride solution, which confirmed the excellent corrosion resistance of the SHP coating. Electrochemical impedance spectroscopy (EIS) studies showed a high impedance modulus for SHP coated surfaces due to the presence of a compact protective layer of cerium myristate. This observed impedance modulus of the SHP surface was approximately four orders higher than the reported value on magnesium alloys. This study provides a new platform for obtaining a robust, mechanically stable, and corrosion resistant SHP coating with a self-cleaning ability on ferritic steel substrates that may be adapted for a range of materials in practical applications.
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http://dx.doi.org/10.1021/acs.langmuir.9b02045DOI Listing
October 2019

Effect of Surface Functionalization and Physical Properties of Nanoinclusions on Thermal Conductivity Enhancement in an Organic Phase Change Material.

ACS Omega 2018 Aug 20;3(8):9487-9504. Epub 2018 Aug 20.

Smart Materials Section, Corrosion Science and Technology Division, Materials Characterization Group, Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, HBNI, Kalpakkam 603102, Tamil Nadu, India.

We probe the role of surface functionalization and physical properties of nanoinclusions in thermal conductivity enhancement during liquid-solid phase transition in a hexadecane-based phase change material (PCM). Hexadecane-based PCM is loaded with six different nanoinclusions: carbon black nanopowder (CBNP), nickel nanoparticles (NiNPs), copper nanoparticles, silver nanowires (AgNWs), multiwalled carbon nanotubes, and graphene nanoplatelets (GNPs). The nanoinclusions CBNP, NiNP, AgNW, and GNP are surface-functionalized with oleic acid. Nanoinclusion-loaded PCM showed a large enhancement in thermal conductivity, which was more prominent in the solid state. Interestingly, a maximum thermal conductivity enhancement of ∼122% was observed in the solid state for the PCM loaded with 0.01 wt % CBNP. Higher thermal conductivity enhancement in the solid state is attributed to the formation of a nanocrystalline network structure during freezing of the PCM, consisting of a needlelike microstructure, which is confirmed by optical phase contrast microscopy. During solidification, the nanoinclusions are driven toward the grain boundaries, thereby forming a quasi-two-dimensional network of percolating structures with high thermal transport efficiency due to the enhancement of phonon-mediated heat transfer and near-field radiative heat transfer. Thermal conductivity increases with the increased loading of the nanoinclusions due to the formation of more interconnecting aggregates. Among the carbon-based nanoinclusions, the highest thermal conductivity enhancement is obtained for the PCM loaded with CBNP, which is attributed to the low fractal dimensions and volume-filling capability of CBNP aggregates. In the case of metallic nanoinclusions, the highest thermal conductivity enhancement is obtained for the PCM loaded with AgNW, which is due to the large aspect ratio of AgNW. The carboxylic group of oleic acid attached to the nanoinclusions is found to provide better steric stability with insignificant aggregation and improved thermal stability, which are beneficial for practical applications. Our results indicate that the initial thermal conductivity of carbon-based nanoinclusions has an insignificant role in the thermal conductivity enhancement of the PCM but the volume-filling capability of the nanoinclusion has a prominent role. The findings from the present study will be beneficial for tailoring the properties of nanoinclusion-loaded organic PCM for thermal energy storage and reversible thermal switching applications at room temperature.
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http://dx.doi.org/10.1021/acsomega.8b01084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644346PMC
August 2018

Real-World Outcomes of an Automated Physician Support System for Genome-Driven Oncology.

JCO Precis Oncol 2019 24;3. Epub 2019 Jul 24.

Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: Matching patients to investigational therapies requires new tools to support physician decision making. We designed and implemented Precision Insight Support Engine (PRECISE), an automated, just-in-time, clinical-grade informatics platform to identify and dynamically track patients on the basis of molecular and clinical criteria. Real-world use of this tool was analyzed to determine whether PRECISE facilitated enrollment to early-phase, genome-driven trials.

Materials And Methods: We analyzed patients who were enrolled in genome-driven, early-phase trials using PRECISE at Memorial Sloan Kettering Cancer Center between April 2014 and January 2018. Primary end point was the proportion of enrolled patients who were successfully identified using PRECISE before enrollment. Secondary end points included time from sequencing and PRECISE identification to enrollment. Reasons for a failure to identify genomically matched patients were also explored.

Results: Data were analyzed from 41 therapeutic trials led by 19 principal investigators. In total, 755 patients were accrued to these studies during the period that PRECISE was used. PRECISE successfully identified 327 patients (43%) before enrollment. Patients were diagnosed with 29 tumor types and harbored alterations in 43 oncogenes, most commonly (21.3%), (14.1%), and (8.7%). Median time from sequencing to enrollment was 163 days (interquartile range, 66 to 357 days), and from PRECISE identification to enrollment 87 days (interquartile range, 37 to 180 days). Common reasons for failing to identify patients before enrollment included accrual on the basis of molecular alterations that did not match pre-established PRECISE genomic eligibility (140 [33%] of 428) and external sequencing not available for parsing (127 [30%] of 428).

Conclusion: PRECISE identified 43% of all patients accrued to a diverse cohort of early-phase, genome-matched studies. Purpose-built informatics platforms represent a novel and potentially effective method for matching patients to molecularly selected studies.
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http://dx.doi.org/10.1200/PO.19.00066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446398PMC
July 2019

Abnormal hemostasis in children with vascular anomalies, part I: Thrombocytopenias among different vascular anomalies.

Thromb Res 2020 12 13;196:626-634. Epub 2019 Jun 13.

Department of Paediatrics, Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address:

Long before the classification of vascular anomalies from the International Society for the Study of Vascular Anomalies (ISSVA) provided a framework to differentiate vascular anomalies, otherwise known as vascular birthmarks, it was recognized that patients with such lesions can present with acute life-threatening hemostatic and/or thrombotic complications, as well as chronic long-standing bleeding or thrombotic issues. Scenarios such as a rapidly growing vascular lesion with severe acute thrombocytopenia, a visceral hemorrhagic lesion, a lesion associated with repetitive and painful superficial thrombosis, and cases of unprovoked or post-procedural fatal pulmonary embolism highlight the wide spectrum of manifestations of abnormal coagulation in patients with vascular anomalies. The separation of vascular anomalies into two distinct groups, vascular tumors and vascular malformations, was followed by the characterization that their respective coagulopathies were due to either a derangement of platelets or to a disequilibrium of the patient's coagulation/fibrinolytic process. This configuration of coagulopathies will be the foundation for this two-chapter review series. In the initial review, coagulopathies where thrombocytopenia is the main feature will be characterized, whereas the second review will focus on vascular malformations that have a coagulation disorder secondary to some degree of coagulation consumption and/or fibrinolytic pathway derangement.
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http://dx.doi.org/10.1016/j.thromres.2019.06.004DOI Listing
December 2020

Clinical, immunophenotypic, and genomic findings of acute undifferentiated leukemia and comparison to acute myeloid leukemia with minimal differentiation: a study from the bone marrow pathology group.

Mod Pathol 2019 09 18;32(9):1373-1385. Epub 2019 Apr 18.

Department of Pathology and Laboratory Medicine, University of Chicago, Chicago, IL, USA.

Acute undifferentiated leukemia is a rare type of acute leukemia that shows no evidence of differentiation along any lineage. Clinical, immunophenotypic and genetic data is limited and it is uncertain if acute undifferentiated leukemia is biologically distinct from acute myeloid leukemia with minimal differentiation, which also shows limited myeloid marker expression and has been reported to have a poor prognosis. We identified 92 cases initially diagnosed as acute undifferentiated leukemia or acute myeloid leukemia with minimal differentiation from pathology databases of nine academic institutions with available diagnostic flow cytometric data, cytogenetic findings, mutational and clinical data. Outcome analysis was performed using Kaplan Meier test for the 53 patients who received induction chemotherapy. Based on cytogenetic abnormalities (N = 30) or history of myelodysplastic syndrome (N = 2), 32 cases were re-classified as acute myeloid leukemia with myelodysplasia related changes. The remaining 24 acute undifferentiated leukemia patients presented with similar age, blood counts, bone marrow cellularity, and blast percentage as the remaining 30 acute myeloid leukemia with minimal differentiation patients. Compared to acute myeloid leukemia with minimal differentiation, acute undifferentiated leukemia cases were characterized by more frequent mutations in PHF6 (5/15 vs 0/19, p = 0.016) and more frequent expression of TdT on blasts (p = 0.003) while acute myeloid leukemia with minimal differentiation cases had more frequent CD123 expression (p = 0.042). Outcome data showed no difference in overall survival, relapse free survival, or rates of complete remission between acute undifferentiated leukemia and acute myeloid leukemia with minimal differentiation groups (p > 0.05). Acute myeloid leukemia with myelodysplasia-related changes patients showed shorter survival when censoring for bone marrow transplant as compared to acute undifferentiated leukemia (p = 0.03) and acute myeloid leukemia with minimal differentiation (p = 0.002). In this largest series to date, the acute undifferentiated leukemia group shows distinct characteristics from acute myeloid leukemia with minimal differentiation, including more frequent PHF6 mutations and expression of TdT.
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http://dx.doi.org/10.1038/s41379-019-0263-3DOI Listing
September 2019

A Novel Approach to Enhance High Temperature Thermal Stability of Superparamagnetic Fe₃O₄ Nanoparticles.

J Nanosci Nanotechnol 2019 Sep;19(9):5624-5632

SMARTS, CSTD, Metallurgy and Materials Group Indira Gandhi Centre for Atomic Research, HBNI, Kalpakkam 603102, India.

We report a novel approach to enhance thermal stability of magnetite nanoparticles by entrapping them in silver matrix. The oleic acid capped nanoparticles of average crystallite size ˜10 nm were synthesized through co-precipitation, followed by hydrothermal microwave assisted capping of magnetite nanoparticles with Ag matrix in ethylene glycol solvent. At ˜160 °C the oleic acid is desorbed from the magnetite nanoparticles, and silver is deposited on negatively charged magnetite seeds through electrostatic attraction. The prepared particles are characterized by X-ray diffraction, high resolution transmission electron microscopy, dynamic light scattering and UV-vis spectroscopy. The surface plasmon resonance band at 479 nm and large average hydrodynamic diameter of ˜432 nm confirm the Ag matrix around the magnetite particles. Thermal stability of prepared particles was assessed using high temperature XRD, thermo gravimetric analysis and differential scanning calorimetry and the results are compared with that of oleic acid capped particles. Magnetite nanoparticles in silver matrix showed no phase conversion up to 900 °C, while oleic acid capped and bare nanoparticles are phase converted to nonmagnetic α-Fe₂O₃ phase between 400-450 °C, under vacuum annealing. A rapid growth of Fe₃O₄ nanoparticles at higher temperature was observed due to faster coalescence through diffusion and higher surface free energy of magnetite as compared to silver. The saturation magnetization of oleic acid capped magnetite particles in silver matrix before and after vacuum annealing at 900 °C were 25.4 and 46.7 emu/g, respectively. The retention of superparamagnetic behavior in silver matrix up to 900 °C is interesting for high temperature applications.
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http://dx.doi.org/10.1166/jnn.2019.16573DOI Listing
September 2019

Use of the Transrectal Ultrasound Probe in Aspiration and Drainage in Pediatric Patients: A Retrospective Observational Study.

J Vasc Interv Radiol 2019 Jun 5;30(6):908-914. Epub 2019 Apr 5.

Division of Image Guided Therapy, Diagnostic Imaging, The Hospital for Sick Children, Department of Medical Imaging, University of Toronto, 555 University Avenue, 2810B, Toronto, Canada M5G 1X8.

Purpose: To retrospectively evaluate the safety and efficacy of transrectal ultrasound (TRUS) probe use for aspiration and drainage of pelvic abscesses in children.

Materials And Methods: Patient demographics, procedural details, technical success, safety, and clinical course of TRUS procedures were retrospectively analyzed. Between 2007 and 2016, 118 TRUS-guided procedures were performed in 115 children (60 males, 55 females); median age was 12.4 years (range, 2.4-17.9 years) and median weight was 45 kg (range, 12.6-112 kg). Ten children were 5 years of age or younger.

Results: In total, 113/118 procedures were performed under general anesthesia. The rectum accommodated the probe and needle guide without resistance in all children (technical feasibility, 100%). Abscesses were anterior to the rectum in 116/118 and posterior in 2/118. One hundred twelve collections were drained, 4 were aspirated, and 2 procedures were aborted, both subsequently successfully drained (2 and 3 days later). One patient underwent repeat drainage after 28 months. No major complications were reported. Median times to temperature normalization was 0 days (mean, 1.2; range, 0-13 days), catheter dwell time 5 days (mean, 6; range, 2-21 days), drain removal to discharge 1 day (mean, 2; range, 0-41 days), and follow-up 117 days (mean, 195; range, 5-2,690 days).

Conclusions: TRUS-guided drainage using the TRUS probe and needle guide is a safe and effective method for aspiration and drainage of pelvic abscesses in children as young as 2 years.
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http://dx.doi.org/10.1016/j.jvir.2018.09.023DOI Listing
June 2019

Growth of Pulmonary Arteriovenous Malformations in Pediatric Patients with Hereditary Hemorrhagic Telangiectasia.

J Pediatr 2019 May 8;208:279-281. Epub 2019 Mar 8.

Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada; Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. Electronic address:

The evolution of pulmonary arteriovenous malformations (PAVMs) over time in children with hereditary hemorrhagic telangiectasia (HHT) is not well-defined. Herein we demonstrate that, although new PAVMs did not evolve in children with HHT, existing PAVMs exhibit quantitative growth over time highlighting the need for ongoing follow-up throughout childhood.
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http://dx.doi.org/10.1016/j.jpeds.2018.12.069DOI Listing
May 2019

Weak localization and small anomalous Hall conductivity in ferromagnetic Weyl semimetal CoTiGe.

Sci Rep 2019 Mar 4;9(1):3342. Epub 2019 Mar 4.

Department of Physics, The Catholic University of America, Washington, DC, 20064, USA.

Several cobalt-based Heusler alloys have been predicted to exhibit Weyl Semimetal behavior due to time reversal symmetry breaking. CoTiGe is one of the predicted ferromagnetic Weyl semimetals. In this work, we report weak localization and small anomalous Hall conductivity in half-metallic CoTiGe thin films grown by molecular beam epitaxy. The longitudinal resistivity shows semimetallic behavior. Elaborate analysis of longitudinal magnetoconductance shows the presence of a weak localization quantum correction present even up to room temperature and reduction in dephasing length at lower temperature. Negative longitudinal magnetoresistance is observed from 5 to 300 K, but at 300 K magnetoresistance becomes positive above 0.5 T magnetic field. The anomalous Hall effect has been investigated in these thin films. The measured anomalous Hall conductivity decreases with increasing temperature, and a small anomalous Hall conductivity has been measured at various temperatures which may be arising due to both intrinsic and extrinsic mechanisms.
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http://dx.doi.org/10.1038/s41598-019-39037-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399263PMC
March 2019

Genetic mechanisms of primary chemotherapy resistance in pediatric acute myeloid leukemia.

Leukemia 2019 08 13;33(8):1934-1943. Epub 2019 Feb 13.

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Acute myeloid leukemias (AML) are characterized by mutations of tumor suppressor and oncogenes, involving distinct genes in adults and children. While certain mutations have been associated with the increased risk of AML relapse, the genomic landscape of primary chemotherapy-resistant AML is not well defined. As part of the TARGET initiative, we performed whole-genome DNA and transcriptome RNA and miRNA sequencing analysis of pediatric AML with failure of induction chemotherapy. We identified at least three genetic groups of patients with induction failure, including those with NUP98 rearrangements, somatic mutations of WT1 in the absence of apparent NUP98 mutations, and additional recurrent variants including those in KMT2C and MLLT10. Comparison of specimens before and after chemotherapy revealed distinct and invariant gene expression programs. While exhibiting overt therapy resistance, these leukemias nonetheless showed diverse forms of clonal evolution upon chemotherapy exposure. This included selection for mutant alleles of FRMD8, DHX32, PIK3R1, SHANK3, MKLN1, as well as persistence of WT1 and TP53 mutant clones, and elimination of FLT3, PTPN11, and NRAS mutant clones. These findings delineate genetic mechanisms of primary chemotherapy resistance in pediatric AML, which should inform improved approaches for its diagnosis and therapy.
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http://dx.doi.org/10.1038/s41375-019-0402-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687545PMC
August 2019