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1.
Blood ; 142(8): 700-710, 2023 08 24.
Article in English | MEDLINE | ID: mdl-37319437

ABSTRACT

In the ABA2 study, the T-cell costimulation blockade agent, abatacept, was safe and effective in preventing acute graft-versus-host disease (aGVHD) after unrelated-donor hematopoietic cell transplant (HCT), leading to US Food and Drug Administration approval. Here, we performed a determination of abatacept pharmacokinetics (PK), which enabled an examination of how abatacept exposure-response relationships affected clinical outcomes. We performed a population PK analysis of IV abatacept using nonlinear mixed-effect modeling and assessed the association between abatacept exposure and key transplant outcomes. We tested the association between the trough after dose 1 (Ctrough_1) and grade (GR) 2 or 4 aGVHD (GR2-4 aGVHD) through day +100. An optimal Ctrough_1 threshold was identified via recursive partitioning and classification tree analysis. This demonstrated that abatacept PK was characterized by a 2-compartment model with first-order elimination. The ABA2 dosing regimen was based on previous work targeting a steady-state abatacept trough of 10 µg/mL. However, a higher Ctrough_1 (≥39 µg/mL, attained in ∼60% of patients on ABA2) was associated with a favorable GR2-4 aGVHD risk (hazard ratio, 0.35; 95% confidence interval, 0.19-0.65; P < .001), with a Ctrough_1 <39 µg/mL associated with GR2-4 aGVHD risk indistinguishable from placebo (P = .37). Importantly, no significant association was found between Ctrough_1 and key safety indicators, including relapse, and cytomegalovirus or Epstein-Barr virus viremia. These data demonstrate that a higher abatacept Ctrough_1 (≥39 µg/mL) was associated with a favorable GR2-4 aGVHD risk, without any observed exposure-toxicity relationships. This trial was registered at www.clinicaltrials.gov as #NCT01743131.


Subject(s)
Epstein-Barr Virus Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Abatacept/adverse effects , Epstein-Barr Virus Infections/etiology , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Herpesvirus 4, Human
2.
Small ; 18(6): e2105776, 2022 02.
Article in English | MEDLINE | ID: mdl-34821030

ABSTRACT

The spatial and compositional complexity of 3D structures employed in today's nanotechnologies has developed to a level at which the requirements for process development and control can no longer fully be met by existing metrology techniques. For instance, buried parts in stratified nanostructures, which are often crucial for device functionality, can only be probed in a destructive manner in few locations as many existing nondestructive techniques only probe the objects surfaces. Here, it is demonstrated that grazing exit X-ray fluorescence can simultaneously characterize an ensemble of regularly ordered nanostructures simultaneously with respect to their dimensional properties and their elemental composition. This technique is nondestructive and compatible to typically sized test fields, allowing the same array of structures to be studied by other techniques. For crucial parameters, the technique provides sub-nm discrimination capabilities and it does not require access-limited large-scale research facilities as it is compatible to laboratory-scale instrumentation.


Subject(s)
Nanostructures , Nanostructures/chemistry , Nanotechnology
3.
Proc Natl Acad Sci U S A ; 116(23): 11165-11170, 2019 06 04.
Article in English | MEDLINE | ID: mdl-31110011

ABSTRACT

The source of water (H2O) and hydroxyl radicals (OH), identified on the lunar surface, represents a fundamental, unsolved puzzle. The interaction of solar-wind protons with silicates and oxides has been proposed as a key mechanism, but laboratory experiments yield conflicting results that suggest that proton implantation alone is insufficient to generate and liberate water. Here, we demonstrate in laboratory simulation experiments combined with imaging studies that water can be efficiently generated and released through rapid energetic heating like micrometeorite impacts into anhydrous silicates implanted with solar-wind protons. These synergistic effects of solar-wind protons and micrometeorites liberate water at mineral temperatures from 10 to 300 K via vesicles, thus providing evidence of a key mechanism to synthesize water in silicates and advancing our understanding on the origin of water as detected on the Moon and other airless bodies in our solar system such as Mercury and asteroids.

4.
Pestic Biochem Physiol ; 186: 105174, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35973765

ABSTRACT

The cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is one of the most destructive agricultural pests due to photosynthate removal and horizontal transmission of plant viruses. Horizontal transmission of plant viruses by aphids occurs during distinct feeding behavioral events, such as probing for non-persistent viruses or phloem feeding for persistent viruses. We employed toxicity bioassays and electrical penetration graph (EPG) methodology to compare toxicity and quantify changes to feeding behavior and toxicity of A. gossypii after exposure to commercialized aphicides. Commercialized aphicides containing flupyradifurone, sulfoxaflor, thiamethoxam, thiamethoxam + lambda cyhalothrin, and bifenthrin induced >90% aphid mortality within 4 h of exposure. Flupyradifurone was the most acutely toxic aphicide studied with an LT50 of 8.9 min after exposure, which was approximately 3-fold lower than bifenthrin and thiamethoxam + lambda cyhalothrin. This was supported by our EPG results that showed a significant reduction in the proportion of aphids that continued to probe on cotton 4 h after exposure to flonicamid, thiamethoxam, flupyradifurone, bifenthrin, and thiamethoxam + lambda cyhalothrin. The commercialized aphicides containing spirotetramat, flonicamid, thiamethoxam, flupyradifurone, bifenthrin, sulfoxaflor, and pymetrozine significantly (P < 0.05) decreased the time to first probe when compared to the untreated control. Lastly, E1 (phloem salivation) and E2 (phloem ingestion) waveforms were significantly (P < 0.05) reduced for flupyradifurone, flonicamid, thiamethoxam, sulfoxaflor, and thiamethoxam. These data provide a comparative study for the development of new aphicides aiming to induce acute lethality and reduce aphid transmission of plant viruses.


Subject(s)
Aphids , Insecticides , Animals , Feeding Behavior , Insecticides/toxicity , Survivorship , Thiamethoxam
5.
Plant Physiol ; 182(4): 2111-2125, 2020 04.
Article in English | MEDLINE | ID: mdl-32051180

ABSTRACT

Aminophospholipid ATPases (ALAs) are lipid flippases involved in transporting specific lipids across membrane bilayers. Arabidopsis (Arabidopsis thaliana) contains 12 ALAs in five phylogenetic clusters, including four in cluster 3 (ALA4-ALA7). ALA4/5 and ALA6/7, are expressed primarily in vegetative tissues and pollen, respectively. Previously, a double knockout of ALA6/7 was shown to result in pollen fertility defects. Here we show that a double knockout of ALA4/5 results in dwarfism, characterized by reduced growth in rosettes (6.5-fold), roots (4.3-fold), bolts (4.5-fold), and hypocotyls (2-fold). Reduced cell size was observed for multiple vegetative cell types, suggesting a role for ALA4/5 in cellular expansion. Members of the third ALA cluster are at least partially interchangeable, as transgenes expressing ALA6 in vegetative tissues partially rescued ala4/5 mutant phenotypes, and expression of ALA4 transgenes in pollen fully rescued ala6/7 mutant fertility defects. ALA4-GFP displayed plasma membrane and endomembrane localization patterns when imaged in both guard cells and pollen. Lipid profiling revealed ala4/5 rosettes had perturbations in glycerolipid and sphingolipid content. Assays in yeast revealed that ALA5 can flip a variety of glycerolipids and the sphingolipid sphingomyelin across membranes. These results support a model whereby the flippase activity of ALA4 and ALA5 impacts the homeostasis of both glycerolipids and sphingolipids and is important for cellular expansion during vegetative growth.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , Hypocotyl/genetics , Hypocotyl/metabolism , Sphingolipids/metabolism
6.
Blood ; 132(17): 1737-1749, 2018 10 25.
Article in English | MEDLINE | ID: mdl-30154114

ABSTRACT

The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD4+ and CD4+CD45RA+ cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD4+ cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Hematopoietic Stem Cell Transplantation , Immune Reconstitution/immunology , Severe Combined Immunodeficiency/genetics , Severe Combined Immunodeficiency/mortality , Severe Combined Immunodeficiency/therapy , Genotype , Humans , Lymphocyte Count , Retrospective Studies
7.
Int J Syst Evol Microbiol ; 70(6): 3639-3646, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32501783

ABSTRACT

A Gram-stain-negative, microaerophilic, non-motile, rod-shaped bacterium strain designated PMP191FT, was isolated from a human peritoneal tumour. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the organism formed a lineage within the family Chitinophagaceae that was distinct from members of the genus Pseudoflavitalea (95.1-95.2 % sequence similarity) and Pseudobacter ginsenosidimutans (94.4 % sequence similarity). The average nucleotide identity values between strain PMP191FT and Pseudoflavitalea rhizosphaerae T16R-265T and Pseudobacter ginsenosidimutans Gsoil 221T was 68.9 and 62.3% respectively. The only respiratory quinone of strain PMP191FT was MK-7 and the major fatty acids were iso-C15 : 0, iso-C15 : 1 G and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The polar lipids consisted of phosphatidylethanolamine and some unidentified amino and glycolipids. The G+C content of strain PMP191FT calculated from the genome sequence was 43.4 mol%. Based on phylogenetic, phenotypic and chemotaxonomic evidence, strain PMP191FT represents a novel species and genus for which the name Parapseudoflavitalea muciniphila gen. nov., sp. nov. is proposed. The type strain is PMP191FT (=DSM 104999T=ATCC BAA-2857T = CCUG 72691T). The phylogenetic analyses also revealed that Pseudobacter ginsenosidimutans shared over 98 % sequence similarly to members of the genus Pseudoflavitalea. However, the average nucleotide identity value between Pseudoflavitalea rhizosphaerae T16R-265T, the type species of the genus and Pseudobacter ginsenosidimutans Gsoil 221T was 86.8 %. Therefore, we also propose that Pseudobacter ginsenosidimutans be reclassified as Pseudoflavitalea ginsenosidimutans comb. nov.


Subject(s)
Bacteroidetes/classification , Peritoneal Neoplasms/microbiology , Phylogeny , Bacterial Typing Techniques , Bacteroidetes/isolation & purification , Baltimore , Base Composition , DNA, Bacterial/genetics , Fatty Acids/chemistry , Glycolipids/chemistry , Humans , Phosphatidylethanolamines/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Vitamin K 2/analogs & derivatives , Vitamin K 2/chemistry
8.
Pediatr Blood Cancer ; 67(4): e28167, 2020 04.
Article in English | MEDLINE | ID: mdl-31925920

ABSTRACT

We describe 12 pediatric patients (8-16 years) with primary refractory (N = 6) or first relapse (N = 6) Hodgkin lymphoma (HL) treated with ifosfamide, gemcitabine, and vinorelbine (IGEV). The overall response rate to IGEV was 100%, with seven (58%) complete responses (CR) and five (42%) partial responses. Successful CD34+ stem cell mobilization was achieved in all patients. Following subsequent autologous stem cell transplantation, 10 patients (83%) achieved CR. At a median follow-up of 71 months, 11 patients had no evidence of disease. Five-year second event-free survival and overall survival were 83% ± 11.0% and 90.0% ± 9.5%, respectively. IGEV is an effective salvage regimen for children with relapsed/refractory HL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Hematopoietic Stem Cell Mobilization , Hodgkin Disease , Salvage Therapy , Stem Cell Transplantation , Adolescent , Autografts , Child , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Female , Hodgkin Disease/mortality , Hodgkin Disease/therapy , Humans , Ifosfamide/administration & dosage , Male , Survival Rate , Vinorelbine/administration & dosage , Gemcitabine
9.
J Opt Soc Am A Opt Image Sci Vis ; 37(9): 1417-1422, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32902429

ABSTRACT

When encoding diffractive lenses onto a spatial light modulator (SLM), there is a Nyquist limit to the smallest focal length that can be formed. When this limit is surpassed, a two-dimensional array of lenslets is formed. There have been very few discussions on the performance of these lenslets. In this work, we focus on the phase distribution of these lenses in the array. We show that, for certain values of the focal length, the lenslets are all in perfect phase. We show that this situation happens for a total number of N/4 different discrete equidistant sub-Nyquist focal lengths, where N×N is the number of pixels in the SLM. We find other distances in between where the array is composed of two sets of lenslets with a relative π phase among them. Finally, we illustrate these phase distributions in the application to generate an array of vortex producing lenses. We expect that these results might be useful for high-accuracy interferometric or multiple imaging where this phase must be exactly the same for each replica.

10.
Arch Toxicol ; 94(7): 2413-2421, 2020 07.
Article in English | MEDLINE | ID: mdl-32388820

ABSTRACT

Previous rat toxicity studies of alpha-glycosyl isoquercitrin (AGIQ), a water-soluble flavonol glycoside derived from rutin, revealed systemic yellow bone discoloration. This investigative study was conducted to determine the AGIQ metabolite(s) responsible for the discoloration. Female Sprague-Dawley rats were administered dietary AGIQ at doses of 0%, 1.5%, 3.0%, or 5.0% (0, 1735.0, 3480.8, and 5873.7 mg/kg/day, respectively) for 14 days, followed by a 14- or 28-day recovery period. Measurements of quercetin in urine and quercetin, quercetin 3-O-glucuronide, kaempferol, and 3-o-methylquercetin metabolites of AGIQ in bone (femur), white and brown fat, and cerebrum samples were conducted following the exposure period and each recovery period. Gross examination of the femur revealed yellow discoloration that increased in intensity with dose and was still present in a dose-related manner following both recovery periods. Quercetin, at levels correlating with AGIQ dose, was measured in the urine following the 14-day exposure period and, at lower concentrations, 14 or 28 days following cessation of AGIQ exposure. All four metabolites were present in a dose-dependent manner in the femur following 14 days of dietary exposure; only quercetin, quercetin 3-O-glucuronide, and 3-o-methylquercetin were present during the recovery periods. Quercetin, quercetin 3-O-glucuronide, and 3-o-methylquercetin were detected in white fat (along with kaempferol), brown fat (excluding quercetin due to analytical interference), and cerebrum samples, indicating systemic availability of the metabolites. Collectively, these data implicate quercetin, quercetin 3-O-glucuronide, or 3-o-methylquercetin (or a combination thereof) as the most likely metabolite of AGIQ causing the yellow discoloration of bone in rats administered dietary AGIQ.


Subject(s)
Femur/drug effects , Pigmentation Disorders/chemically induced , Pigmentation/drug effects , Quercetin/toxicity , Animals , Biotransformation , Female , Femur/pathology , Pigmentation Disorders/pathology , Quercetin/analogs & derivatives , Quercetin/metabolism , Rats, Sprague-Dawley , Time Factors
11.
Int J Mol Sci ; 21(4)2020 Feb 18.
Article in English | MEDLINE | ID: mdl-32085403

ABSTRACT

The neurotransmitter levels of representatives from five different diagnosis groups were tested before and after participation in the MNRI®-Masgutova Neurosensorimotor Reflex Intervention. The purpose of this study was to ascertain neurological impact on (1) Developmental disorders, (2) Anxiety disorders/OCD (Obsessive Compulsive Disorder), PTSD (Post-Traumatic Stress disorder), (3) Palsy/Seizure disorders, (4) ADD/ADHD (Attention Deficit Disorder/Attention Deficit Disorder Hyperactive Disorder), and (5) ASD (Autism Spectrum Disorder) disorders. Each participant had a form of neurological dysregulation and typical symptoms respective to their diagnosis. These diagnoses have a severe negative impact on the quality of life, immunity, stress coping, cognitive skills, and social assimilation. This study showed a trend towards optimization and normalization of neurological and immunological functioning, thus supporting the claim that the MNRI method is an effective non-pharmacological neuromodulation treatment of neurological disorders. The effects of MNRI on inflammation have not yet been assessed. The resulting post-MNRI changes in participants' neurotransmitters show significant adjustments in the regulation of the neurotransmitter resulting in being calmer, a decrease of hypervigilance, an increase in stress resilience, behavioral and emotional regulation improvements, a more positive emotional state, and greater control of cognitive processes. In this paper, we demonstrate that the MNRI approach is an intervention that reduces inflammation. It is also likely to reduce oxidative stress and encourage homeostasis of excitatory neurotransmitters. MNRI may facilitate neurodevelopment, build stress resiliency, neuroplasticity, and optimal learning opportunity. There have been no reported side effects of MNRI treatments.


Subject(s)
Inflammation/pathology , Neurotransmitter Agents/metabolism , Adolescent , Adult , Attention Deficit Disorder with Hyperactivity/physiopathology , Attention Deficit Disorder with Hyperactivity/therapy , Autism Spectrum Disorder/physiopathology , Autism Spectrum Disorder/therapy , Dopamine/metabolism , Epinephrine/biosynthesis , Histamine/metabolism , Humans , Reflex/physiology , Serotonin Plasma Membrane Transport Proteins/metabolism , Young Adult
12.
Biol Blood Marrow Transplant ; 25(3): 556-561, 2019 03.
Article in English | MEDLINE | ID: mdl-30321596

ABSTRACT

Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for many nonmalignant disorders (NMD) and is curative or prevents disease progression. Reduced-intensity conditioning (RIC) in HSCT for NMD may reduce regimen-related acute toxicities and late complications. Myeloablation is often replaced by immune suppression in RIC regimens to support donor engraftment. The pace of immune reconstitution after immune suppression by RIC regimens is influenced by agents used, donor source, and graft-versus-host disease prophylaxis/treatment. In a multicenter trial (NCT 00920972) of HSCT for NMD, a RIC regimen consisting of alemtuzumab, fludarabine, and melphalan was substituted for myeloablation. Alemtuzumab was administered early (days -21 to -19) to mitigate major lymphodepletion of the incoming graft and the risk of graft rejection. Immune reconstitution and infectious complications were prospectively monitored for 1-year post-HSCT. Seventy-one patients met inclusion criteria for this report and received marrow or peripheral blood stem cell transplants. Immune reconstitution and infections are reported for related donor (RD) and unrelated donor (URD) transplants at 3 time-points (100days, 6 months, and 1 year post-HSCT). Natural killer cell recovery was rapid, and numbers normalized in both cohorts by day +100. Mean CD3, CD4, and CD8 T-lymphocyte numbers normalized by 6 months after RD HSCT and by 1 year in the URD group. CD4 and CD8 T-lymphocyte counts were significantly higher in patients who received RD HSCT at 6 months and at 1 year, respectively, post-HSCT compared with patients who received URD HSCT. The pace of CD19 B-cell recovery was markedly different between RD and URD cohorts. Mean B-cell numbers were normal by day 100 after RD HSCT but took 1 year post-HSCT to normalize in the URD cohort. Despite these differences in immune reconstitution, the timing and nature of infections did not differ between the groups, presumably because of comparable T-lymphocyte recovery. Immune reconstitution occurred at a faster pace than in prior reports using RIC with T-cell depletion. The incidence of infections was similar for both cohorts and occurred most frequently in the first 100days post-HSCT. Viral and fungal infections occurred at a lower incidence in this cohort, with "early" alemtuzumab compared with regimens administering serotherapy in the peritransplantation period. Patients were susceptible to bacterial infections primarily in the first 100days irrespective of donor source and had no increase in mortality from the same. The overall mortality rate from infections was 1.4% at 1 year. Close monitoring and prophylaxis against bacterial infections in the first 100days post-HSCT is necessary but is followed by robust immune reconstitution, especially in the T-cell compartment.


Subject(s)
Alemtuzumab/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Immune Reconstitution , Infections/etiology , Transplantation Conditioning/methods , Alemtuzumab/adverse effects , Child , Female , Graft Survival , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Lymphocyte Depletion , Male , Survival Analysis , Unrelated Donors
13.
Opt Express ; 27(3): 2374-2386, 2019 Feb 04.
Article in English | MEDLINE | ID: mdl-30732276

ABSTRACT

The robustness of the polarization spatial distribution of vector beams upon propagation is crucial for a number of applications, including optical communications and materials processing. This study has been commonly centered on Gouy phase effects on focused vector beams. In this work, we present a theoretical and experimental analysis of the Gouy phase's effects on the propagation of pure and hybrid vector beams. Experimental results at various axial planes, before and past the focus, are obtained by using a simplified liquid-crystal spatial light modulator-based optical system that allows the easy generation of these beams. Furthermore, a new alternative optical set-up that is devoid of moving elements is demonstrated, which simplifies this study. We experimentally verify the differences between pure and hybrid vector beams upon propagation. While the first ones remain stable, hybrid vector beams show Gouy phase effects that demonstrate an optical activity where the local polarization states rotate by an angle that depends on the propagation distance. Experimental results agree with the theory.

14.
Opt Lett ; 44(13): 3398-3401, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-31259970

ABSTRACT

Liquid crystal displays allow the easy implementation of diffractive optical elements. However, the shortest focal lengths for lenses are limited by Nyquist conditions. In this work, we show that focal lengths much lower than this Nyquist limit can be encoded onto devices having a large phase-dynamic range. Experimental results are included with a display showing 10π phase modulation reducing the Nyquist limit by a factor of about 1/10.

15.
Appl Opt ; 58(17): 4585-4591, 2019 Jun 10.
Article in English | MEDLINE | ID: mdl-31251274

ABSTRACT

Multimode optical fibers are gaining increased interest for higher data rate transmissions. In this work, we examine the propagation of beams in multimode optical fibers using the angular spectrum method for several values for the propagation constant V. We prepare a sequence of 4096 images over 200,000 steps, each representing a wavelength within the fiber. We perform a one-dimensional Fourier transform of these data and obtain the propagation constant for each transmitted mode. We then obtain the electric field profile for each transmitted mode. We find excellent agreement with weakly guided mode theory. This work represents another step in the use of this algorithm for analyzing more complicated optical fiber structures.

16.
Clin Infect Dis ; 67(4): 485-492, 2018 08 01.
Article in English | MEDLINE | ID: mdl-29617957

ABSTRACT

Background: During the 2014-2015 influenza season in the United States, 256 cases of influenza-associated parotitis were reported from 27 states. We conducted a case-control study and laboratory investigation to further describe this rare clinical manifestation of influenza. Methods: During February 2015-April 2015, we interviewed 50 cases (with parotitis) and 124 ill controls (without parotitis) with laboratory-confirmed influenza; participants resided in 11 states and were matched by age, state, hospital admission status, and specimen collection date. Influenza viruses were characterized using real-time polymerase chain reaction and next-generation sequencing. We compared cases and controls using conditional logistic regression. Specimens from additional reported cases were also analyzed. Results: Cases, 73% of whom were aged <20 years, experienced painful (86%), unilateral (68%) parotitis a median of 4 (range, 0-16) days after onset of systemic or respiratory symptoms. Cases were more likely than controls to be male (76% vs 51%; P = .005). We detected influenza A(H3N2) viruses, genetic group 3C.2a, in 100% (32/32) of case and 92% (105/108) of control specimens sequenced (P = .22). Influenza B and A(H3N2) 3C.3 and 3C.3b genetic group virus infections were detected in specimens from additional cases. Conclusions: Influenza-associated parotitis, as reported here and in prior sporadic case reports, seems to occur primarily with influenza A(H3N2) virus infection. Because of the different clinical and infection control considerations for mumps and influenza virus infections, we recommend clinicians consider influenza in the differential diagnoses among patients with acute parotitis during the influenza season.


Subject(s)
Influenza, Human/complications , Parotitis/virology , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Infant , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/isolation & purification , Male , Middle Aged , Parotitis/diagnosis , Parotitis/epidemiology , Seasons , United States , Young Adult
17.
Clin Infect Dis ; 67(4): 493-501, 2018 08 01.
Article in English | MEDLINE | ID: mdl-29617951

ABSTRACT

Background: During the 2014-2015 US influenza season, 320 cases of non-mumps parotitis (NMP) among residents of 21 states were reported to the Centers for Disease Control and Prevention (CDC). We conducted an epidemiologic and laboratory investigation to determine viral etiologies and clinical features of NMP during this unusually large occurrence. Methods: NMP was defined as acute parotitis or other salivary gland swelling of >2 days duration in a person with a mumps- negative laboratory result. Using a standardized questionnaire, we collected demographic and clinical information. Buccal samples were tested at the CDC for selected viruses, including mumps, influenza, human parainfluenza viruses (HPIVs) 1-4, adenoviruses, cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses (HSVs) 1 and 2, and human herpes viruses (HHVs) 6A and 6B. Results: Among the 320 patients, 65% were male, median age was 14.5 years (range, 0-90), and 67% reported unilateral parotitis. Commonly reported symptoms included sore throat (55%) and fever (48%). Viruses were detected in 210 (71%) of 294 NMP patients with adequate samples for testing, ≥2 viruses were detected in 37 samples, and 248 total virus detections were made among all samples. These included 156 influenza A(H3N2), 42 HHV6B, 32 EBV, 8 HPIV2, 2 HPIV3, 3 adenovirus, 4 HSV-1, and 1 HSV-2. Influenza A(H3N2), HHV6B, and EBV were the most frequently codetected viruses. Conclusions: Our findings suggest that, in addition to mumps, clinicians should consider respiratory viral (influenza) and herpes viral etiologies for parotitis, particularly among patients without epidemiologic links to mumps cases or outbreaks.


Subject(s)
Influenza, Human/complications , Influenza, Human/epidemiology , Parotitis/virology , Viruses/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mumps , Parotitis/epidemiology , Pharyngitis/virology , Seasons , Surveys and Questionnaires , United States/epidemiology , Young Adult
18.
Biol Blood Marrow Transplant ; 24(10): 2040-2046, 2018 10.
Article in English | MEDLINE | ID: mdl-29933069

ABSTRACT

We enrolled 150 patients in a prospective multicenter study of children with acute myeloid leukemia undergoing hematopoietic stem cell transplantation (HSCT) to compare the detection of measurable residual disease (MRD) by a "difference from normal" flow cytometry (ΔN) approach with assessment of Wilms tumor 1 (WT1) gene expression without access to the diagnostic specimen. Prospective analysis of the specimens using this approach showed that 23% of patients screened for HSCT had detectable residual disease by ΔN (.04% to 53%). Of those patients who proceeded to transplant as being in morphologic remission, 10 had detectable disease (.04% to 14%) by ΔN. The disease-free survival of this group was 10% (0 to 35%) compared with 55% (46% to 64%, P < .001) for those without disease. The ΔN assay was validated using the post-HSCT specimen by sorting abnormal or suspicious cells to confirm recipient or donor origin by chimerism studies. All 15 patients who had confirmation of tumor detection relapsed, whereas the 2 patients with suspicious phenotype cells lacking this confirmation did not. The phenotype of the relapse specimen was then used retrospectively to assess the pre-HSCT specimen, allowing identification of additional samples with low levels of MRD involvement that were previously undetected. Quantitative assessment of WT1 gene expression was not predictive of relapse or other outcomes in either pre- or post-transplant specimens. MRD detected by ΔN was highly specific, but did not identify most relapsing patients. The application of the assay was limited by poor quality among one-third of the specimens and lack of a diagnostic phenotype for comparison.


Subject(s)
Flow Cytometry , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Transplantation Conditioning , Unrelated Donors , WT1 Proteins/blood , Adolescent , Adult , Allografts , Child , Child, Preschool , Disease-Free Survival , Female , Humans , Infant , Infant, Newborn , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Male , Neoplasm, Residual , Transplantation, Homologous
19.
Appl Opt ; 57(19): 5319-5327, 2018 Jul 01.
Article in English | MEDLINE | ID: mdl-30117823

ABSTRACT

We examine single-mode optical fiber transmission using the angular spectrum method. We find excellent agreement with the theoretical solutions for the cylindrical single-mode optical fiber. Next, we examine fiber coupler configurations with 1×2, 1×3, and 1×5 designs. The input within the central fiber core is broadcast equally into the surrounding fiber cores and then returns with propagation distances as expected. Then we examine supermode theory for the 1×3 case. The initial energy is sent into different combinations of fiber cores where their phase relationship governs the output. Surprisingly, we find evidence of an unexpected mode in some of the multicore designs. We expect these results might be useful for exploration of more complicated fiber core arrays. However, computational times are short using this algorithm.

20.
Appl Opt ; 57(5): 1005-1010, 2018 Feb 10.
Article in English | MEDLINE | ID: mdl-29469877

ABSTRACT

We encode q-plates where the angular orientation of the principal axis is varied spatially with a nonstandard distribution. In the usual q-plate design, the orientation of the optical axis depends linearly on the azimuthal angle. In this work, we examine cases where this azimuthal dependence is nonlinear. We consider two cases: first, where the principal axis distribution is like an inverse-tangent function of the azimuth; and second, where it displays linear and flat segments. This last case is proposed as a new method for encoding binary data into the azimuthal lobes of the vector beam. We encode these patterns using a spatial light modulator system that allows new and exotic q-plate designs without the difficulty of fabricating individual plates. Experimental results are presented.

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