Robustness and stability of doubly periodic patterns of the focusing nonlinear Schrödinger equation.

The nonlinear Schrödinger equation possesses doubly periodic solutions expressible in terms of the Jacobi elliptic functions. Such solutions can be realized through doubly periodic patterns observed in experiments in fluid mechanics and optics. Stability and robustness of these doubly periodic wave profiles in the focusing regime are studied computationally by using two approaches. First, linear stability is considered by Floquet theory. Growth will occur if the eigenvalues of the monodromy matrix are of a modulus larger than unity. This is verified by numerical simulations with input patterns of different periods. Initial patterns associated with larger eigenvalues will disintegrate faster due to instability. Second, formation of these doubly periodic patterns from a tranquil background is scrutinized. Doubly periodic profiles are generated by perturbing a continuous wave with one Fourier mode, with or without the additional presence of random noise. Effects of varying phase difference, perturbation amplitude, and randomness are studied. Varying the phase angle has a dramatic influence. Periodic patterns will only emerge if the perturbation amplitude is not too weak. The growth of higher-order harmonics, as well as the formation of breathers and repeating patterns, serve as a manifestation of the classical problem of Fermi-Pasta-Ulam-Tsingou recurrence.

Survival Analysis as a Basis for Testing Hypotheses when Using Quantitative Ordinal Scale Disease Severity Data.

Disease severity in plant pathology is often measured by the amount of a plant or plant part that exhibits disease symptoms. This is typically assessed using a numerical scale, which allows a standardized, convenient, and quick method of rating. These scales, known as quantitative ordinal scales (QOS), divide the percentage scale into a predetermined number of intervals. There are various ways to analyze these ordinal data, with traditional methods involving the use of midpoint conversion to represent the interval. However, this may not be precise enough, as it is only an estimate of the true value. In this case, the data may be considered interval-censored, meaning that we have some knowledge of the value but not an exact measurement. This type of uncertainty is known as censoring, and techniques that address censoring, such as survival analysis (SA), use all available information and account for this uncertainty. To investigate the pros and cons of using SA with QOS measurements, we conducted a simulation based on three pathosystems. The results showed that SA almost always outperformed midpoint conversion with data analyzed using a t test, particularly when data were not normally distributed. Midpoint conversion is currently a standard procedure. In certain cases, the midpoint approach required a 400% increase in sample size to achieve the same power as the SA method. However, as the mean severity increases, fewer additional samples are needed (approximately an additional 100%), regardless of the assessment method used. Based on these findings, we conclude that SA is a valuable method for enhancing the power of hypothesis testing when analyzing QOS severity data. Future research should investigate the wider use of survival analysis techniques in plant pathology and their potential applications in the discipline.

Experiences that matter in bipolar disorder: a qualitative study using the capability, comfort and calm framework.

BACKGROUND: When assessing the value of an intervention in bipolar disorder, researchers and clinicians often focus on metrics that quantify improvements to core diagnostic symptoms (e.g., mania). Providers often overlook or misunderstand the impact of treatment on life quality and function. We wanted to better characterize the shared experiences and obstacles of bipolar disorder within the United States from the patient's perspective. METHODS: We recruited 24 individuals diagnosed with bipolar disorder and six caretakers supporting someone with the condition. Participants were involved in treatment or support services for bipolar disorder in central Texas. As part of this qualitative study, participants discussed their everyday successes and obstacles related to living with bipolar disorder during personalized, open-ended interviews. Audio files were transcribed, and Nvivo software processed an initial thematic analysis. We then categorized themes into bipolar disorder-related obstacles that limit the patient's capability (i.e., function), comfort (i.e., relief from suffering) and calm (i.e., life disruption) (Liu et al., FebClin Orthop 475:315-317, 2017; Teisberg et al., MayAcad Med 95:682-685, 2020). We then discuss themes and suggest practical strategies that might improve the value of care for patients and their families. RESULTS: Issues regarding capability included the struggle to maintain identity, disruptions to meaningful employment, relationship loss and the unpredictable nature of bipolar disorder. Comfort related themes included the personal perception of diagnosis, social stigma and medication issues. Calm themes included managing dismissive doctors, finding the right psychotherapist and navigating financial burdens. CONCLUSIONS: Qualitative data from patients with bipolar disorder helps identify gaps in care or practical limitations to treatment. When we listen to these individuals, it is clear that treatments must also address the unmet psychosocial impacts of the condition to improve patient care, capability and calm.

Validity and severity thresholds for the depression subscale of the affective self rating scale: An equipercentile equating study using classical test theory.

BACKGROUND: The Affective Symptoms Scale (ASRS) is a unique instrument designed to separately measure depressive and manic symptoms in mood disorders. We validated the ASRS against the Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS-16). METHODS: A retrospective study of 258 patients who completed the PHQ-9, QIDS-16 and ASRS as part of routine clinical care. To establish meaningful clinical thresholds for the depression subscale of the ASRS, it was equated with the QIDS and the PHQ-9. RESULTS: The depression subscale of the ASRS had significant positive correlations with the QIDS-16 and the PHQ-9 (respectively, r= 0.8, t[253] = 19.8, p < 0.001, and r= 0.8, t[245] = 28.2, p < 0.001). The equipercentile equating method with the PHQ-9 indicated that the thresholds corresponded to ASRS depression subscale scores of 5.4, 10.6, 16.1, and 23. Equating with the QIDS indicated that thresholds corresponded to ASRS depression subscale scores of 5.1, 11, 18.4, and 27.5. LIMITATIONS: Limitations include a small sample size that did not allow more detailed statistical analysis, such as Item Response Theory. The population is a heterogenous population at a university outpatient setting. CONCLUSIONS: The ASRS depression subscale significantly correlated with the PHQ-9 and QIDS-16. Our proposed threshold scores for the ASRS are 5, 11, 16 and 23 to indicated mild, moderate, severe and very severe depression respectively.

Pediatric hematology/oncology healthcare professional emotional health during COVID-19.

OBJECTIVES: Little is known about the impact of coronavirus disease 2019 (COVID-19) on healthcare professional emotional health in pediatric hematology/oncology. Primary objective was to describe anxiety, depression, positive affect, and perceived stress among pediatric hematology/oncology healthcare professionals following a COVID-19 outbreak. Secondary objectives were to compare these outcomes based on contact with a positive person, and to identify risk factors for worse outcomes. MATERIALS AND METHODS: We included 272 healthcare professionals working with pediatric hematology/oncology patients. We determined whether respondents had direct or indirect contact with a COVID-19-positive individual and then measured outcomes using the Patient-Reported Outcomes Measurement Information System (PROMIS) depression, anxiety, and positive affect measures, and the Perceived Stress Scale. RESULTS: Among eligible respondents, 205 agreed to participate (response rate 75%). Sixty-nine (33.7%) had contact with a COVID-19-positive person. PROMIS anxiety, depression, and positive affect scores were similar to the general United States population. Those who had contact with a COVID-19-positive individual did not have significantly different outcomes. In multiple regression, non-physicians had significantly increased anxiety (nurses: p = 0.013), depression (nurses: p = 0.002, pharmacists: p = 0.038, and other profession: p = 0.021), and perceived stress (nurses: p = 0.002 and other profession: p = 0.011) when compared to physicians. CONCLUSIONS: Pediatric hematology/oncology healthcare professionals had similar levels of anxiety, depression, and positive affect as the general population. Contact with a COVID-19-positive individual was not significantly associated with outcomes. Non-physician healthcare professionals had more anxiety, depression, and perceived stress when compared to physicians. These findings may help to develop programs to support healthcare professional resilience.

Organised hematoma mimicking sino-nasal malignancy in patients post-radiotherapy.

INTRODUCTION: Organised hematoma (OH) in the para-nasal sinus and nasal cavity is a rare, non-neoplastic, benign disease which can be locally aggressive. In clinical practice, OH is easily misdiagnosed as malignancy and over-treated. CASE SUMMARY: These patients with OH had a common history of malignant neoplasms post-radiotherapy, including two cases of nasopharyngeal carcinoma and one case of tonsil cancer with jaw osteosarcoma. All of the patients presented with symptoms of epistaxis and blood-tinged rhinorrhea. All of the patients received endoscopic endonasal surgery under navigation. DISCUSSION: All of the patients had a good recovery after surgery. There's no recurrence after follow-up at 6 months. We therefore hypothesised that radiotherapy could be a cause of the OH. Although OH is uncommon and difficult to diagnose, a history of malignancy and imaging features with appropriate treatment are key.

Quantitative Ordinal Scale Estimates of Plant Disease Severity: Comparing Treatments Using a Proportional Odds Model.

Studies in plant pathology, agronomy, and plant breeding requiring disease severity assessment often use quantitative ordinal scales (i.e., a special type of ordinal scale that uses defined numeric ranges); a frequently used example of such a scale is the Horsfall-Barratt scale. Parametric proportional odds models (POMs) may be used to analyze the ratings obtained from quantitative ordinal scales directly, without converting ratings to percent area affected using range midpoints of such scales (currently a standard procedure). Our aim was to evaluate the performance of the POM for comparing treatments using ordinal estimates of disease severity relative to two alternatives, the midpoint conversions (MCs) and nearest percent estimates (NPEs). A simulation method was implemented and the parameters of the simulation estimated using actual disease severity data from the field. The criterion for comparison of the three approaches was the power of the hypothesis test (the probability to reject the null hypothesis when it is false). Most often, NPEs had superior performance. The performance of the POM was never inferior to using the MC at severity <40%. Especially at low disease severity (≤10%), the POM was superior to using the MC method. Thus, for early onset of disease or for comparing treatments with severities <40%, the POM is preferable for analyzing disease severity data based on quantitative ordinal scales when comparing treatments and at severities >40% is equivalent to other methods.

Hemophagocytic lymphohistiocytosis is a sign of poor outcome in pediatric Epstein-Barr virus-associated post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation.

EBV-related PTLD developing after HSCT is a potentially life-threatening disease. HLH is uncommon after allogeneic HSCT. Data on outcome of patients with PTLD and concomitant HLH after allogeneic HSCT are limited. In this retrospective study, we collected demographic, clinical, laboratory, and outcome data for 408 patients who underwent allogeneic HSCT from 2006 to 2015. Graft source included CB (n = 135; 33.1%), PBSCs (n = 34; 8.3%), and BM (n = 239; 58.6%). Eight out of 408 patients (2%) developed EBV-PTLD with a median age at HSCT of 5.9 years (range: 2.3-17.3). All eight patients received ATG as part of the conditioning regimen. Graft source was PBSC in three patients (37.5%), BM in four patients (50%), and CB in one patient (12.5%). Donors were matched unrelated in five patients (62.5%) and matched sibling in three patients (37.5%). Seven out of eight patients developed EBV-PTLD within the first 100-day post-HSCT. Lymph node biopsy revealed early lesions in three patients, polymorphic in three patients, and monomorphic PTLD in two patients. Three patients (37.5%) died within 1 month of EBV-PTLD diagnosis. All deceased patients developed HLH manifestations with two of them meeting HLH diagnostic criteria and one having an incomplete workup. PTLD after allogeneic HSCT with manifestations of HLH is associated with high mortality. Early identification and treatment of EBV-PTLD seems imperative to control the disease, especially if signs of HLH are evolving.

Collection of hematopoietic stem cells and immune effector cells in small children.

Apheresis procedures are standard of care for a wide range of indications in children, collection of hematopoietic stem cells being the most frequent one. With increasing numbers of hematopoietic stem cell transplants, advances in graft manipulation techniques and the development of innovative therapies using immune effector cells and gene therapy, apheresis within the pediatric population is growing in demand. While young children have higher circulating white blood cell counts and robustly mobilize hematopoietic stem cells, apheresis machines were designed for use within the adult population and apheresis procedures in children, particularly small children, can be more challenging as vascular access, collection techniques and impact of extracorporeal volumes increase the rate of adverse events. In this article we review topics of particular relevance to hematopoietic stem cell and immune effector cell collections in small children.

Epidemiology, risk factors and characteristics of pediatric stroke: a nationwide population-based study.

BACKGROUND: Stroke, classically characterized as an acute acquired neurological deficit, is an important leading cause of death and chronic morbidity in children. AIMS: This study reported the period prevalence, incidence and risk factors of pediatric stroke in Taiwan. METHODS AND PROCEDURES: All Taiwan inhabitants aged 1 month to 18 years registered in the National Health Insurance Research Database between 2010 and 2011 were enrolled in this study. Factors including age, sex, location and household income levels were collected. Incidence, period prevalence, mortality rate and the possible risks were completely evaluated. Outcomes and results: Hemorrhagic stroke has a significantly higher mortality rate than ischemic stroke (27.6% vs. 10.2%, P<0.05). Risk factors or underlying diseases for stroke were identified in 77.8% of the patients and 16.2% had more than one risk factor. The most common risk factors were vascular diseases (26.3%), infection (14.0%) and cardiac disorders (9.1%). CONCLUSIONS AND IMPLICATIONS: Infants younger than 2 years, boys and children in lower socioeconomic status have a significantly higher risk of stroke. Hemorrhagic stroke has a significantly higher mortality rate than ischemic stroke. More than half of the children with stroke had underlying diseases and the causes of hemorrhagic stroke are significantly different from ischemic stroke.

The utility of routine pre-chemotherapy screening with cardiac gated blood pool scan for patients at low risk of anthracycline toxicity.

Background Anthracycline-based chemotherapy is used in many malignancies. Current recommendations by several groups suggest cardiac monitoring prior to and during anthracycline therapy. We aim to review the usefulness of baseline cardiac screening for left ventricular ejection fraction to assess if it had any impact on chemotherapy decisions in patients to be treated with anthracycline-based regimens or any beneficial effect upon outcomes. Methods We conducted a retrospective three-year audit of cancer patients who underwent GBPS prior to anthracycline (doxorubicin) chemotherapy. Subjects were identified via records from the Department of Nuclear Medicine. Pharmacy dispensing records identified those who received doxorubicin. Patient demographics, cancer type, cardiac risk factors, GBPS ejection fraction (EF), and cumulative anthracycline dose were collected. Results From 1 August 2009 to 31 July 2012, 179 patients underwent GBPS pre-doxorubicin chemotherapy. The mean age was 59 years (range 21-89 years), with 51% being males. Only two patients (1.1%) had an abnormal EF < 50%, while 33 patients (18%) had an EF 51-59% and 144 patients (80%) had EF ≥ 60%. The two patients with reduced baseline EF still received anthracycline-based chemotherapy. All 135 patients without any known cardiovascular risk factors had normal EFs. The total number of patients who received anthracycline chemotherapy during the same period was 207. Thus 28 patients (13%) commenced anthracycline without a prior GBPS. Conclusion Only 1.1% of the screened patients had EF < 50%. These two patients still received doxorubicin chemotherapy despite a compromised EF, as their treating clinicians believed that the benefits of chemotherapy outweighed the risk of potential cardiac toxicity. Our audit questions the practice of routine cardiac evaluation pre-anthracycline screening with GBPS. We propose that routine screening only be requested if cardiac risk factors are present.

Hard-hard coupling assisted anomalous magnetoresistance effect in amine-ended single-molecule magnetic junction.

We proposed a single-molecule magnetic junction (SMMJ), composed of a dissociated amine-ended benzene sandwiched between two Co tip-like nanowires. To better simulate the break junction technique for real SMMJs, the first-principles calculation associated with the hard-hard coupling between a amine-linker and Co tip-atom is carried out for SMMJs with mechanical strain and under an external bias. We predict an anomalous magnetoresistance (MR) effect, including strain-induced sign reversal and bias-induced enhancement of the MR value, which is in sharp contrast to the normal MR effect in conventional magnetic tunnel junctions. The underlying mechanism is the interplay between four spin-polarized currents in parallel and anti-parallel magnetic configurations, originated from the pronounced spin-up transmission feature in the parallel case and spiky transmission peaks in other three spin-polarized channels. These intriguing findings may open a new arena in which magnetotransport and hard-hard coupling are closely coupled in SMMJs and can be dually controlled either via mechanical strain or by an external bias.

A Multicenter Retrospective Analysis Stressing the Importance of Long-Term Follow-Up after Hematopoietic Cell Transplantation for ß-Thalassemia.

Allogeneic hematopoietic cell transplantation (HCT) is curative in patients with ß-thalassemia major. However, most reports on HCT outcomes lack long-term follow-up data with the exception of single-center reports. An international multicenter retrospective data collection and analysis was conducted in 176 ß-thalassemia patients who were 1 year or beyond after first HCT to evaluate follow-up methods and outcomes at 7 centers. Median age at HCT was 5.5 years (range, .6 to 18.5), and median follow-up was 7 years (range, 1 to 20). HCT was predominantly from HLA-matched related donors (91%) with bone marrow as stem cell source (91%) and myeloablative conditioning regimens (88%). Late mortality or persistent chronic graft-versus-host disease (GVHD) was rare (<2%). Graft rejection was reported in 23% (24% of these occurred beyond 1 year) post-HCT. Of 119 patients with donor chimerism results available for ≥4 years post-HCT, 50% had >95%, 22% had 50% to 95%, 7% had 20% to 50% and 25 (21%) had <20% donor chimerism. Organ dysfunction was identified in 10% pre-HCT and in 20% post-HCT even without complete clinical details on all patients. Hypogonadism and elevated creatinine for age were most commonly reported and significantly higher in recipients ≥ 7 years at the time of HCT (P = .007) and in those with pre-existing morbidity before HCT (P = .02). Outcomes were unaffected by pre-HCT ferritin or GVHD. Mean z scores for height and weight were low at baseline and remained low post-HCT (79%), confirming that growth impairment from disease lacked recovery post-HCT during this follow-up period. HCT for ß-thalassemia has a high rate of cure and low mortality, especially in the young and from HLA-matched related donors. Half of the number of recipients live with mixed chimerism that requires continued follow-up because of a risk of late graft rejection (14%). Organ function after HCT when <7 years of age was generally preserved. Hypogonadism, renal dysfunction, and growth impairment that failed to correct were late complications identified most frequently in older transplant recipients. Systematic follow-up of individual organs such as lung and heart were inadequate but important. These data support the development of simple measures of uniformly tracking long-term HCT outcomes and organ functions in children and adolescents who undergo HCT for thalassemia, allowing for systematic identification and implementation of standardized surveillance strategies and interventions.

Entropy production and irreversibility of dissipative trajectories in electric circuits.

We experimentally examine the equivalence between the entropy production evaluated from irreversibility of trajectories and the physical dissipation in dissipative processes via electric resistor-capacitor (RC) circuits. The examinations are performed for two nonequilibrium steady states that are driven by an injected current and temperature difference, respectively. Such an equivalence demonstrates a parameter-free method to evaluate the entropy production of a system. The effects of configurational and temporal resolutions are also studied.

Electrical autonomous Brownian gyrator.

We study experimentally and theoretically the steady-state dynamics of a simple stochastic electronic system featuring two resistor-capacitor circuits coupled by a third capacitor. The resistors are subject to thermal noises at real temperatures. The voltage fluctuation across each resistor can be compared to a one-dimensional Brownian motion. However, the collective dynamical behavior, when the resistors are subject to distinct thermal baths, is identical to that of a Brownian gyrator, as first proposed by Filliger and Reimann [Phys. Rev. Lett. 99, 230602 (2007)PRLTAO0031-900710.1103/PhysRevLett.99.230602]. The average gyrating dynamics is originated from the absence of detailed balance due to unequal thermal baths. We look into the details of this stochastic gyrating dynamics, its dependences on the temperature difference and coupling strength, and the mechanism of heat transfer through this simple electronic circuit. Our work affirms the general principle and the possibility of a Brownian ratchet working near room temperature scale.

Epidermal growth factor-induced ANGPTL4 enhances anoikis resistance and tumour metastasis in head and neck squamous cell carcinoma.

Epidermal growth factor (EGF) is important for cancer cell proliferation, angiogenesis and metastasis in many types of cancer. However, the mechanisms involved in EGF-induced head and neck squamous cell carcinoma (HNSCC) metastasis remain largely unknown. In this study, we reveal that angiopoietin-like 4 (ANGPTL4) plays an important role in the regulation of EGF-induced cancer metastasis. We showed that EGF-induced ANGPTL4 expression promoted anoikis resistance and cancer cell migration and invasion in HNSCC. In addition, depletion of ANGPTL4 inhibited EGF-induced cancer cell invasion. Autocrine production of EGF-induced ANGPTL4 regulated the expression of matrix metalloproteinases (MMPs). The induction of MMP-1 gene expression by ANGPTL4-activated integrin ß1 signalling occurred through the AP-1 binding site in the MMP-1 gene promoter. Furthermore, down-regulation of MMP-1 impeded EGF- and recombinant ANGPTL4-enhanced HNSCC cell migration and invasion. Depletion of ANGPTL4 significantly blocked EGF-primed extravasation and metastatic seeding of tumour cells and MMP-1 expression in lungs. However, no effect of ANGPTL4 on tumour growth was observed. These results suggest that EGF-induced expression and autocrine production of ANGPTL4 enhances HNSCC metastasis via the up-regulation of MMP-1 expression. Inhibition of ANGPTL4 expression may be a potential strategy for the treatment of EGFR-mediated HNSCC metastasis.

The safety of autologous and metabolically fit bone marrow mesenchymal stromal cells in medically refractory Crohn's disease - a phase 1 trial with three doses.

BACKGROUND: Mesenchymal stromal cells ability to reset immune functionalities may be useful in Crohn's disease. AIM: To perform a first-in-human phase 1 safety clinical trial of metabolically fit autologous bone marrow-derived mesenchymal stromal cells in 12 subjects with Crohn's disease utilising three doses. METHODS: Autologous mesenchymal stromal cells were derived from marrow aspirate and propagated for 2-3 weeks with fibrinogen depleted human platelet lysate and subsequently administered to subjects without interval cryobanking. Twelve subjects received a single mesenchymal stromal cell intravenous infusion of 2, 5 or 10 million cells/kg BW(n = 4/group). Infused mesenchymal stromal cells were analysed for cell surface marker expression, IDO(indoleamine 2,3-dioxygenase) upregulation by IFNγ stimulation, and inhibition of third party peripheral blood mononuclear cell proliferation in vitro. The primary end point measured was safety and tolerability; clinical response was assessed as a secondary endpoint. RESULTS: All patients tolerated the mesenchymal stromal cell infusion well and no dose limiting toxicity was seen. Seven patients had serious adverse events of which five were hospitalisations for Crohn's disease flare. Two of these serious adverse events were possibly related to the mesenchymal stromal cells infusion. Five subjects showed clinical response 2 weeks after the infusion. Mesenchymal stromal cell phenotype, cytokine responsiveness, and peripheral blood mononuclear cell proliferation blockade were not different among the patients. CONCLUSION: Single infusion of fresh autologous bone marrow mesenchymal stromal cells propagated ex vivo using human platelet lysate-supplemented media was safe and feasible at intravenous doses of up to 10 million cells/kg BW in patients with Crohn's disease.