Onset Of Initiation Research Articles

Temperature dependent two-body abrasive wear of polycarbonate surfaces

During the lifetime of polycarbonate surfaces, which for example are used as helmets or protective eye visors, friction and abrasive wear may result from scratching or sliding cycles. Previous research showed that it is essential to understand the intrinsic mechanical response of the polymer in order to further investigate its frictional and wear response. The Eindhoven Glassy Polymer (EGP) model is a 3D elasto-viscoplastic constitutive model, developed to describe the intrinsic mechanical response of polymer glasses. Temperature is a crucial player in the intrinsic response and also plays a pivotal role in the resulting frictional response as tested via a single-asperity scratch test. In the current study, a finite element model is used to investigate the effect of temperature on the frictional response of polycarbonate and detect the onset of crack formation and wear initiation. The results show that temperature has a strong effect on the intrinsic response of the polymer, i.e. drop in yield stress and altered strain-hardening and strain-softening response. However, it has a minute effect on its frictional response, the simulation model is able to capture this response quantitively. In addition, cracks are observed experimentally at elevated temperature. A critical positive hydrostatic stress value is selected as a criterion for crack formation. It has been shown that at elevated temperatures the value of the maximum positive hydrostatic stress increases due to the altered intrinsic response of the material on one hand, and the increased adhesion between the tip and the polymer on the other hand.

Late Onset of Estrogen Therapy Impairs Carotid Function of Senescent Females in Association with Altered Prostanoid Balance and Upregulation of the Variant ERα36.

Recent analysis of clinical trials on estrogen therapy proposes the existence of a therapeutic window of opportunity for the cardiovascular benefits of estrogens, which depend on women’s age and the onset of therapy initiation. In this study, we aimed to determine how vascular senescence and the onset of estrogen treatment influence the common carotid artery (CCA) function in senescent and non-senescent females. Ovariectomized female senescence-accelerated (SAMP8) or non-senescent (SAMR1) mice were treated with vehicle (OVX) or 17β-estradiol starting at the day of ovariectomy (early-onset, E2E) or 45 days after surgery (late-onset, E2L). In SAMR1, both treatments, E2E and E2L, reduced constriction to phenylephrine (Phe) in CCA [(AUC) OVX: 193.8 ± 15.5; E2E: 128.1 ± 11.6; E2L: 130.2 ± 15.8, p = 0.004] in association with positive regulation of NO/O2- ratio and increased prostacyclin production. In contrast, E2E treatment did not modify vasoconstrictor responses to Phe in OVX-SAMP8 and, yet, E2L increased Phe vasoconstriction [(AUC) OVX: 165.3 ± 10; E2E: 183.3 ± 11.1; E2L: 256.3 ± 30.4, p = 0.005]. Increased vasoconstriction in E2L-SAMP8 was associated with augmented thromboxane A2 and reduced NO production. Analysis of wild-type receptor alpha (ERα66) expression and its variants revealed an increased expression of ERα36 in E2L-SAMP8 in correlation with unfavorable effects of estrogen in those animals. In conclusion, estrogen exerts beneficial effects in non-senescent CCA, regardless of the initiation of the therapy. In senescent CCA, however, estrogen loses its beneficial action even when administered shortly after ovariectomy and may become detrimental when given late after ovariectomy. Aging and onset of estrogen treatment are two critical factors in the mechanism of action of this hormone in CCA.

Identifying factors associated with treatment delay in leptospirosis: A retrospective study of patients admitted to hospital in Reunion (Indian Ocean) between 2014 and 2015

BackgroundLeptospirosis is a life-threatening zoonotic disease for which delayed treatment onset has been associated to poor prognosis. The purpose of the study was to identify the determinants of therapeutic delay in hospitalized leptospirosis cases. Patients and methodsWe carried out a retrospective multicenter study in the 4 public hospitals of Reunion Island, South Western Indian Ocean. Medical records of confirmed leptospirosis cases occurring in 2014–2015 were reviewed for socio-economic, demographic, geographic and medical data. The primary outcome measure was the therapeutic delay, defined as the time elapsed between the onset of symptoms and initiation of antibiotics. ResultsOf the 117 patients included, 107 were men, with an average age of 44.9±15years. The median therapeutic delay was 4 days (interquartile: 2–5 days) and this delay was not found to be associated with severity. The following were found to be at increased risk of having a longer therapeutic delay: cases occurring outside the epidemic period, or rainy season (OR 2.8 [1.08–7.3], P=0.04) and cases with first medical evaluation in primary health care (OR 4.63 [1.43–14.93]; P=0.01) instead of emergency unit. No socio-economic or geographic characteristics were found to be linked to a longer therapeutic delay. ConclusionAlthough delayed treatment was not associated to disease severity, our results indicate that leptospirosis awareness is needed all year in the subtropical area of Reunion Island and particularly in primary care.

Analysis of deficit irrigation strategies by using SUBSTOR-Potato model in a semi-arid area

AbstractIn areas where water is scarce, the use of regulated deficit irrigation, combined with decision support system tools, may decrease the impact of agriculture on natural water resources, as well as on energy consumption, thereby improving the profitability of farms. With this aim, the SUBSTOR-Potato model (incorporated in the DSSAT Program) was evaluated with a 2-year field test (2011 and 2012) conducted in a semi-arid area (Albacete, Spain) applying four irrigation levels (120, 100, 80 and 60% of irrigation requirements). Subsequently, the model was used for simulating the potato yield under several deficit irrigation strategies (ISs) during 30 years of a semi-arid climate (1988–2017) and determining the most profitable option. The considered ISs were deemed those most suitable from the yield and water productivity point of view by some authors. The model performance for tuber yield was satisfactory with an index of agreement >0.91 and errors between 0.71 and 3.06 × 103 kg/ha. The ISs simulated with SUBSTOR-Potato showed that slight deficit irrigation (5–10%) may increase the water productivity and profitability of the farms. Moreover, tuber formation (from onset of tuber initiation to harvest) was shown to be the most sensitive stage, therefore it is highly recommended to avoid deficit during this stage, which would cause a large reduction in yield (around 8 t/ha, depending on the level of deficit suffered by the crop).

Predicting fatigue crack initiation from coupled microstructure and corrosion morphology effects

The onset of fatigue crack initiation is driven by the microstructure and the corrosion morphology; however, these mechanisms are rarely studied synergistically. In this work, characterizations of the microstructural features and the corrosion morphology resulting from two different environmental exposures are instantiated into crystal plasticity models. Fatigue indicator parameters (FIPs) are calculated from the micromechanical fields to quantify failure. The FIPs compare favorably to predict the experimentally observed location of fatigue crack initiation. These results show the potential behind analyzing environmentally-assisted fatigue crack initiation from a multivariable perspective.

Failure Studies of Selectively Heated Sintered P/M Al–4 wt% Ti Composite During Cold Axial Forming

In the upsetting process, flow of metal starts from centre region to outer region and failure occurs due to nucleation of void, growth of void and finally void coalescence into micro-crack. These micro-cracks extend in the hoop direction and fracture occurs at the equatorial region due to the presence of accumulated stresses. Hence, the failure of the components strongly depends on the stress accumulated on the failure zone. In the present work, the failure zone was identified through upsetting experiments on powder metallurgical Al–4 wt% Ti composites that have different initial relative densities and an aspect ratio of 1. It was found that the failure occurs at the equatorial region due to accumulation of maximum principal stresses. These accumulated stresses affect the failure limit of the work piece during cold upsetting. Hence, it is necessary to relieve these accumulated stresses for better failure limit in various engineering applications. Thus, this work is aimed at relieving the accumulated stresses on the failure zone by heating selectively on the region where more work hardening has taken place during the deformation stage. As the heating has been performed only at selected locations, the mechanical properties of the samples are not expected to deteriorate due to the heating step. As a result, initiation and progression of failure can be delayed by selective heating before the onset of failure initiation. Selective heating relieve the accumulated stresses and delay the failure onset, thereby increasing the failure limit of the metal.

Evidence that systemic therapies for psoriasis may reduce psoriatic arthritis occurrence

Contemporary biologic therapies for psoriasis are independently licensed for psoriatic arthritis (PsA). Since skin disease generally predates PsA and PsA has a subclinical phase, we investigated the pattern of PsA evolution in psoriasis treated with biologic agents compared to other medications including oral therapy, topical agents or no treatments. A retrospective chart review was performed in psoriasis patients with musculoskeletal symptoms referred for rheumatological assessment. Patients who had a final diagnosis of PsA were identified. The frequency and clinical features of PsA were compared for biologics versus the other strategies. Between 2015-18, 203 psoriasis patients were referred for musculoskeletal symptoms with 25 on biologics, 31 on non-biologic systemic therapies and 147 on topical/no therapies. A final diagnosis of PsA was similar in all groups (biologics: 36%; non-biologic systemic treatments: 35.4%; none/local treatments: 37.4%). Most patients had musculoskeletal symptoms before systemic therapy initiation but new onset PsA was evident in 12% (3/25) biologics treated patients, 9.6% (3/31) in non-biologic systemic therapy patients and was significantly higher in patients on topical/no therapy (55/147; 37.4%, p<0.001). Among patients with PsA, none of the patients on biologics exhibited dactylitis compared to 28.6% of other systemic treatments and 48.6% of none/local treatments (p=0.046). New symptoms and signs leading to PsA diagnosis appear to decrease with systemic treatments. The characteristic PsA dactylitis lesion was not evident in the biologic therapy group.

PS1548 SAFETY AND EFFICACY OF CANNABIDIOL FOR SEVERE ACUTE GRAFT VERSUS HOST DISEASE - A PHASE I/II STUDY

Background: Steroid refractory severe (grade 3–4) acute graft vs. host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplant (allo-HCT) and thus represents a major unmet medical need. Cannabidiol (CBD), a safe and non-psychotropic ingredient of marijuana, has been shown to exhibit potent immune-modulatory and anti-inflammatory properties in various inflammatory diseases including in GVHD setting, as reported by us in 2015. Aims: to examine the safety and efficacy of CBD for the treatment of steroid refractory severe acute GVHD Methods: We conducted a phase 1/2 prospective study (NCT 02392780). Upon recruitment, CBD was orally administered at a dose of 150 mg twice daily for up to 90 days. First line treatment consisting of cyclosporine or tacrolimus and high-dose methylprednisolone was continued, and tapered off slowly according to clinical response. Study endpoints included cumulative incidence of patients achieving either very good partial response (VGPR) or complete response (CR) and patients achieving partial response (PR) of their GVHD. Further endpoints included incidence of chronic GVHD and safety. Results: Between June 2014 and November 2016, 10 consecutive patients with severe acute GVHD following allo-HCT for hematological malignancy were enrolled (median age = 59, range, 31–70 years). Most patients had acute leukemia (9/10). All donors were HLA matched- sibling (5/10) or unrelated (5/10). Conditioning regimen was mostly myeloablative (8/10), with primary GVHD prophylaxis consisting of cyclosporine A and methotrexate (9/10). Acute GVHD occurred after donor lymphocyte infusion (DLI) for relapse of hematological malignancy in 4/10 patients: in 3/10 it appeared within day 100 of transplantation and in 3/10 during immunosuppression tapering off. Median duration between onset of GVHD and CBD initiation was 13 (range 5–52) days. Patients received CBD for a median of 84 days (range 11–258). Overall, CBD was well tolerated and no grade 3–4 toxicities were attributed to CBD. One patient (#10) developed severe sepsis 5 days from enrollment, and died 16 days later. Among the 9 evaluable patients, 8/9 responded to the treatment and achieved either CR (6/9) or VGPR (2/9). All responses were durable, apart from one patient (#2) who decided to stop treatment with a subsequent flare-up of fatal acute GvHD. In all responders (8/9), response to treatment was noted already one week after CBD initiation. Mean time to best response was 45.9 days with a median of 37 days (SD = 32.1, range 3–97). All responders could decrease substantially immunosuppressive treatment. None of the patients developed chronic GVHD while consuming CBD. Only one patient (#6) developed chronic GVHD, involving eye and mouth, after CBD cessation. Median follow up was 7 months (range 21 days - 46 months). At last follow up, 3 patients were alive, all in CR without acute or chronic GVHD at a median of 4.7 years post-transplant (range 4–6 years). Two patients died of relapse (#07 who was transplanted with refractory disease; #08 whose GvHD developed after relapse and DLI). Three patients died of late infectious complications (more than 6 months after enrollment).Summary/Conclusion: Considering the dismal prognosis of patients with severe refractory acute GVHD, the results of this study are encouraging, albeit with the limitation of our small sample size. Further prospective studies are warranted to confirm these preliminary results.

130-OR: Does the Duration of Prediabetes Status Affect Reversibility with Lifestyle Intervention?

Background: Intensive lifestyle intervention (ILI) prevents progression from prediabetes (Predm) to type 2 diabetes (T2D). Here we assessed reversion to normal glucose regulation (NGR) following ILI. Subjects and Methods: The PROP-ABC (Pathobiology and Reversibility of Prediabetes in a Biracial Cohort) study followed an established cohort of African Americans (AA) and European Americans (EA) with parental T2D for 5 years and initiated ILI in subjects with Predm and those with newly incident Predm. ILI was started after variable intervals from onset of Predm, targeting 10% weight loss through calorie restriction, physical activity, and meal replacements. Serial assessments included anthropometry, fasting plasma glucose (FPG) and lipid levels, OGTT, IVGTT and insulin sensitivity. The primary endpoint was reversion to NGR. Results: We studied 210 PROP-ABC participants: mean (SD) age 53.3(9.28) y; BMI 30.6(6.70) kg/m2; 70% female, 52.4% AA, 47.6% EA. Predm subjects (N=138) initiated ILI after a latency of 4.08 (2.02) years (range 3 months-8 years), and were stratified into &amp;lt; 3 years (n=32), 3-5 years (n=59) or &amp;gt;5 years (n=47), between onset of Predm and initiation of ILI. Control (N=72) were NGR subjects not receiving ILI. After 5y, FPG (-6.91±1.13 mg/dl vs.1.23 ± 1.43 mg/dl, P=0.0008), 2hPG (-8.23 ±3.27 mg/dl vs.-4.90 ± 8.63 mg/dl, P=0.08) and weight (-2.64 ± 0.85 kg vs. 1.24±1.13 kg, P= 0.04) decreased among ILI participants vs. control. Reversion to NGR occurred in 43.5%, stable Predm in 50%, and T2D in 6.5%. These outcomes did not differ significantly by time to initiation of ILI (chi-square P=0.901). Reversion to NGT occurred within 12 months of ILI and was significantly predicted by BMI, waist size, insulin sensitivity, insulin secretion, and HDL-c (P= 0.04-0.001). Conclusion: Starting ILI within 3 months to 8 years of occurrence of prediabetes prevented T2D in &amp;gt;90% and restored NGR in ~44% of AA and EA subjects with parental T2D, regardless of time to initiation of ILI. Disclosure N.A. Umekwe: None. I. Owei: None. A.A. Brewer: None. L. French: None. D.J. James: None. F. Ariganjoye: None. S. Dagogo-Jack: Board Member; Self; Jana Care Inc. Consultant; Self; Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Sanofi-Aventis. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Stock/Shareholder; Self; Dance Biopharm Holdings Inc. Funding National Institutes of Health (R01DK067269)

Diversification of cytokinin phosphotransfer signaling genes in Medicago truncatula and other legume genomes

BackgroundLegumes can establish on nitrogen-deprived soils a symbiotic interaction with Rhizobia bacteria, leading to the formation of nitrogen-fixing root nodules. Cytokinin phytohormones are critical for triggering root cortical cell divisions at the onset of nodule initiation. Cytokinin signaling is based on a Two-Component System (TCS) phosphorelay cascade, involving successively Cytokinin-binding Histidine Kinase receptors, phosphorelay proteins shuttling between the cytoplasm and the nucleus, and Type-B Response Regulator (RRB) transcription factors activating the expression of cytokinin primary response genes. Among those, Type-A Response Regulators (RRA) exert a negative feedback on the TCS signaling. To determine whether the legume plant nodulation capacity is linked to specific features of TCS proteins, a genome-wide identification was performed in six legume genomes (Cajanus cajan, pigeonpea; Cicer arietinum, chickpea; Glycine max, soybean; Phaseolus vulgaris, common bean; Lotus japonicus; Medicago truncatula). The diversity of legume TCS proteins was compared to the one found in two non-nodulating species, Arabidopsis thaliana and Vitis vinifera, which are references for functional analyses of TCS components and phylogenetic analyses, respectively.ResultsA striking expansion of non-canonical RRBs was identified, notably leading to the emergence of proteins where the conserved phosphor-accepting aspartate residue is replaced by a glutamate or an asparagine. M. truncatula genome-wide expression datasets additionally revealed that only a limited subset of cytokinin-related TCS genes is highly expressed in different organs, namely MtCHK1/MtCRE1, MtHPT1, and MtRRB3, suggesting that this “core” module potentially acts in most plant organs including nodules.ConclusionsFurther functional analyses are required to determine the relevance of these numerous non-canonical TCS RRBs in symbiotic nodulation, as well as of canonical MtHPT1 and MtRRB3 core signaling elements.

Sicca Syndrome Associated with Immune Checkpoint Inhibitor Therapy.

The objective of this study was to characterize the clinicopathologic features of sicca syndrome associated with immune checkpoint inhibitor (ICI) therapy. Consecutive patients with new or worsening xerostomia in the setting of ICI treatment for benign or malignant neoplastic disease were evaluated, including labial salivary gland biopsy (LSGB). Twenty patients (14 male; median age 57 years) had metastatic melanoma (n = 10), metastatic carcinoma (n = 6), or recurrent respiratory papillomatosis (n = 4) and were being treated with avelumab (n = 8), nivolumab (n = 5), pembrolizumab (n = 4), nivolumab/ipilimumab (n = 2), and M7824, a biologic targeting programmed cell death ligand 1 (PD-L1) and transforming growth factor ß (n = 1). Four had pre-existing autoimmune disease. Nineteen had very low whole unstimulated saliva flow; six had new dry eye symptoms. The median interval between ICI initiation and dry mouth onset was 70 days. Rheumatoid factor and anti-Sjögren's Syndrome-related Antigen A (Anti-SSA) were both positive in two subjects. LSGB showed mild-to-severe sialadenitis with diffuse lymphocytic infiltration and architectural distortion. There were lymphocytic aggregates in eight patients, composed mainly of CD3+ T cells with a slight predominance of CD4+ over CD8+ T cells. ICI targets (e.g., programmed cell death 1 and PD-L1) were variably positive. In direct response to the advent of the sicca immune-related adverse event, the ICI was held in 12 patients and corticosteroids were initiated in 10. Subjective improvement in symptoms was achieved in the majority; however, salivary secretion remained very low. ICI therapy is associated with an autoimmune-induced sicca syndrome distinct from Sjögren's syndrome, often abrupt in onset, usually developing within the first 3 months of treatment, and associated with sialadenitis and glandular injury. Improvement can be achieved with a graded approach depending on severity, including withholding the ICI and initiating corticosteroids. However, profound salivary flow deficits may be long term. Sicca syndrome has been reported as an immune-related adverse event (irAE) of immune checkpoint inhibitor therapy (ICI) for neoplastic diseases. Severe dry mouth (interfering with eating or sleeping) developed abruptly, typically within 90 days, after initiation of ICI therapy. Salivary gland biopsies demonstrated mild-to-severe sialadenitis distinct from Sjögren's syndrome, with diffuse T-cell lymphocytic infiltration and acinar injury. Recognition of the cardinal features of ICI-induced sicca will spur appropriate clinical evaluation and management, including withholding of the ICI and corticosteroid, initiation. This characterization should help oncologists, rheumatologists, and oral medicine specialists better identify patients that develop ICI-induced sicca to initiate appropriate clinical evaluation and therapy to reduce the likelihood of permanent salivary gland dysfunction.

Effect of Selective Heating on Formability and Densification of Powder Metallurgy Preforms During Upsetting

In this work, a new method of selective heating is proposed to increase the deformation behaviour of cylindrical sintered aluminium preforms during the process. Initially, cold upsetting is carried out using 0.5 MN hydraulic press machine at 0.1 s−1 strain rate and the failure locations of the preforms are predicted for various initial relative densities with the aspect ratio of 1 during the deformation process. After the prediction of this failure location, various conditions of selective heating are attempted uniformly on the deformed preforms after a certain stage of deformation before the onset of the failure initiation, using portable gas cartridge at a different temperature and time to assess their consequence on formability behaviour. The detailed experimental results are evaluated for the formability of the selectively heated preforms under different variables such as flow stress, relative density, axial strain, formability stress index and stress ratio parameter. As a result, the initiation of failure and its progression can be delayed by selectively heating the samples before the onset of the failure initiation. Selective heating of the failure location may relieve the accumulated stresses and delay the onset of failure to a later strain level thereby increasing the formability of the metal.

Prevalence of Bone Loss and the Short-Term Effect of Anti-retroviral Therapy on Bone Mineral Density in Treatment-Naïve Male Japanese Patients with HIV

Background: There have been few studies have shown the relationship between HIV and low Bone Mineral Density (BMD) in Asian countries. In particular, research on the early impact of anti-HIV drugs on BMD is scarce. Objective: We studied the prevalence of bone loss and changes of BMD after the start of Anti-Retroviral Therapy (ART) in Japanese naïve patients with HIV. Methods: Male patients with HIV who visited our hospital between 2010 and 2016 were enrolled. Patients underwent BMD analyses before and one year after ART. Changes in BMD after ART initiation were evaluated by paired t-tests. To identify clinical factors affecting BMD after ART initiation based on the BMD change ratio, multiple regression analysis was performed. Results: Thirty-one patients were followed up. By employing the T-scores in the lumbar spines and femoral necks, the prevalence of osteopenia and osteoporosis was found to be 38.7-45.2% and 6.2% respectively. There were significant BMD decreases after ART initiation. Use of Tenofovir Disoproxil Fumarate (TDF) / emtricitabine (FTC), use of Protease Inhibitors (PIs), and low CD4 cell counts were independent risk factors for lumbar spine BMD decrease. Urinary N-terminal telopeptide / creatinine was the independent risk factor for femoral neck BMD decrease. Conclusions: Low BMD was prevalent in our study cases. Low CD4 cell counts at the onset of ART initiation, TDF/FTC use, and PI use increased the risk of lumbar spine BMD decrease significantly more, while ART affected femoral neck BMD of patients with higher bone metabolic activity significantly more.

Liver injury by immune checkpoint inhibitors in patients with hepatocellular carcinoma.

341 Background: In patients with hepatocellular carcinoma (HCC) and baseline liver dysfunction, hepatic immune-related adverse events (HIRAEs) during immunotherapy have not been adequately characterized and their impact on subsequent treatment outcomes is not known. Methods: 40 patients with advanced/unresectable HCC and Child Pugh score A have been enrolled in first and second-line clinical trials of anti-programmed cell death protein 1 (PD-1) monoclonal antibodies (mAbs). HCC etiologies were: hepatitis C (32.5%), hepatitis B (7.5%), alcohol abuse (27.5%), other (32.5%). 7 received anti-PD-1 mAbs alone and 33 received combined regimens that included anti-PD-1 mAbs plus either anti-cytotoxic T lymphocyte antigen 4 (30.4%) or tyrosine kinase inhibitors (TKIs) (54.5%), or both (15.1%). We reviewed their liver function tests and HIRAEs onset was related to time to treatment failure (TTF). Results: Overall, 12 patients (30%) developed grade ≥ 3 hepatitis according to Common Toxicity Criteria for Adverse Events v. 4.03, resulting in 4 cases of grade 2 drug-induced liver injury per DILI Working Group criteria. Time between therapy initiation and hepatitis onset was 1.4 months (0.4-2.8) and median peak aminotransferase (AT) level was 258 IU/L (85-869). Out of 6 permanent treatment discontinuations due to adverse events (AEs), 4 were linked to hepatitis. Higher AT median levels at baseline were significantly linked to grade ≥ 3 hepatitis compared with lower grades (95 IU/L vs. 36 IU/L, respectively; p = 0.008). Etiology, age, treatment did not predict HIRAEs onset. TTF in patients in patients with grade ≥ 3 hepatitis was shorter than in the whole cohort (1.4 vs. 3.8 months, p = 0.041), while overall survival did not differ (p = 0.125). Conclusions: We observed a 30% incidence of clinically significant HIRAEs. HIRAEs represent the most frequent AEs leading to treatment discontinuation in patients with HCC undergoing treatments with immune checkpoint inhibitors. Baseline AT levels may identify patients at increased risk of grade ≥ 3 hepatitis.

Multiscale analysis of fatigue crack initiation life for unidirectional composite laminates

Three dimensional (3D) finite element analysis along with a damage model based on kinetic theory of fracture (KTF) are used to determine the onset of fatigue crack initiation in unidirectional carbon fiber reinforced composites. In addition, the Multicontinuum theory (MCT) and micromechanics are employed separately to enable the assessment of the stress state distribution at the length scale level of the constituents. While the MCT is implemented in the macroscale model formulation, micromechanical analysis of a representative unit cell has been also developed to capture the stress field in the micro length scale level. An ABAQUS™ user material (UMAT) subroutine has been developed and used for implementing the formulation. Numerical examples of various tests including tension, three point bending, four point bending, and short beam shear test of a unidirectional (UD) laminate are considered and the results are compared against actual test data. A detailed discussion, challenges and future plans on the applicability of the KTF are concluding this work.

Pulmonary tuberculosis in Uzbekistan

Early diagnosis and prompt effective therapy are crucial for the prevention of tuberculosis (TB) transmission, particularly in regions with high levels of multi-drug resistant TB. This study aimed to evaluate the extent of delay in diagnosis and treatment of TB in Uzbekistan and identify associated risk factors. A cross-sectional study was performed on hospital patients with newly diagnosed TB. The time between the onset of respiratory symptoms and initiation of anti-TB treatment was assessed and delays were divided into patient, health system and total delays. Univariable and multivariable logistic regression analysis was used to evaluate determinants of diagnostic and treatment delay. Among 538 patients enrolled, the median delay from onset of symptoms until treatment with anti-TB drugs was 50 days. Analysis of the factors affecting health-seeking behaviour and timely treatment showed the presence of the patient factor. Self-medication was the first health-seeking action for 231 (43%) patients and proved to be a significant predictor of delay (p = 0.005), as well as coughing (p = 0.009), loss of weight (p = 0.001), and visiting private and primary healthcare facilities (p = 0.03 and p = 0.02, respectively).

Histological and proteomic approaches to study floral bud induction in relation to biennial bearing in apple

Biennial or alternate bearing in fruit trees leads to fluctuating yields, characterized by ‘On’ years with high crop loads followed by ‘Off’ years with little or no yield. To study the mechanism of biennial bearing in apple (Malus domestica Borkh.), the cultivars ‘Royal Gala’ as a regular bearer and ‘Fuji’ as a strongly alternating cultivar were investigated. ‘Off’ trees were completely thinned at full bloom, whereas ‘On’ trees were not thinned to maintain the natural high crop load. The first signs of floral bud initiation were detected for ‘Fuji’ at 70 days after full bloom (DAFB) and 120 DAFB for ‘Off’ and ‘On’ trees, respectively. In ‘Royal Gala’, initiated buds were observed not before 100 DAFB in both treatments. Hence, buds from ‘Fuji’ ‘Off’ trees committed to flowering about one month earlier than those from ‘Royal Gala’ ‘Off’ trees. In contrast, flower initiation of buds from ‘Royal Gala’ ‘On’ trees occurred 20 days earlier when compared to those from ‘Fuji’ ‘On’ trees. Electrospray ionization mass spectrometry (ESI-MS) coupled with ultra-high performance liquid chromatography (UHPLC) allowed the identification of 3011 proteins. A Student’s T-Test revealed 181 differentially expressed proteins between buds from ‘On’ and ‘Off’ trees. Specifically, 81 proteins were significantly upregulated in floral buds and 100 proteins in vegetative buds, respectively. The largest log2 fold change of 3.17 was identified for a zinc metalloprotease in buds from the ‘Fuji’ ‘On’ treatment. The protein with the highest up-regulation in ‘Fuji’ ‘Off’ buds was a nigrin b-like protein. Histological analysis of bud development has proven to be an essential and reliable tool to identify the time point of floral initiation in apple. Moreover, this study demonstrates that especially in biennial bearing cultivars, crop load heavily influences the onset of floral bud initiation and can differ for up to 50 days within the same cultivar depending on crop load. The identification of this critical period enables in-depth analysis of biochemical changes such as differences in protein profiles to further reveal the mechanism of biennial bearing in apple.

Gobbling activity of eastern wild turkeys relative to male movements and female nesting phenology in South Carolina

ABSTRACTWild turkeys (Meleagris gallopavo) use a polygynous mating system, and males must balance fitness benefits of courtship displays against costs of their reproductive strategies. Wild turkeys are the only gamebird species in the contiguous United States hunted primarily during their reproductive period. Managers attempt to implement seasons that allow for hunter satisfaction while limiting effects to reproduction and ensuring sustainable populations. To minimize illegal harvest, managers often attempt to set spring hunting seasons when gobbling activity is high and females are actively incubating nests. Gobbling activity varies significantly both temporally and spatially, and relationships between gobbling activity and reproductive phenology are unclear. We used autonomous recording units and Global Positioning System transmitters to monitor gobbling activity by male eastern wild turkeys (M. g. silvestris) and evaluate fine‐scale movements of male wild turkeys and nesting chronology of females on the Webb Wildlife Management Area Complex in South Carolina, USA, during 2015–2016. Based on 19,126 gobbles and movement ecology data from 99 wild turkeys (70 F, 29 M), we found no discernable pattern to support the hypothesis that gobbling activity increases with onset of incubation by females. We also observed no definable relationship between daily movements of males and gobbling activity, likely driven by the considerable daily variability in gobbling activity. We noted apparent lags in gobbling activity relative to nest initiation (onset of laying), and offer that understanding mechanisms underlying these apparent lags may be important to improving our understanding of reproductive ecology in wild turkeys. Research evaluating confounding influences of hunting activity and male mortality during the breeding season on gobbling activity and wild turkey population dynamics is warranted. © 2018 The Wildlife Society.

Onsets of progression and second treatment determine survival of patients with symptomatic Waldenström macroglobulinemia

AbstractFew reports assess prognosis during follow-up of patients with symptomatic Waldenström macroglobulinemia (WM). In 121 WM patients treated between 1993 and 2016, we analyzed the prognostic role during the clinical course of the initial International Prognostic Scoring System for WM (IPSSWM). Then, we assessed onset of response, progression, and second treatment initiation coded as time-dependent covariates. High-risk IPSSWM was an adverse prognostic factor for survival after first treatment initiation (SAFTI). Nevertheless, the corresponding Dxy concordance index obtained in multiple landmark analyses decreased from 0.24 to 0.08 during the first 6 years, in accordance with a departure from the proportional hazard assumption. By contrast with onset of response (whatever its level), onset of progression and initiation of second-line treatment retained prognostic value for SAFTI (P = .02 and P = .006, respectively). These findings were confirmed in cause-specific Cox models for deaths related to WM, but not for unrelated deaths. Time to progression after first-line treatment and time to initiation of second-line treatment had no prognostic value for survival after these 2 events. These results were confirmed in an independent series of 119 patients homogeneously treated with chemoimmunotherapy. Finally, after second-line and third-line treatment, onset of progression had significant prognostic value for subsequent risk of related death only. Thus, taking initial IPSSWM and delayed response to treatment into account, only onset of progression and second treatment initiation provided additional prognostic information for SAFTI. Therefore, progression-free survival or time to next treatment may be satisfactory surrogate end points of SAFTI in WM.

Numerical Investigation of Rainfall-Induced Landslide in Mudstone Using Coupled Finite and Discrete Element Analysis

In this study, the role of water infiltration on a rainfall-induced landslide in mudstone is investigated. Finite element analysis (FEA) and discrete element analysis (DEA) were employed to explore the driving mechanism in the prefailure regime and the dynamic runout process in the postfailure regime, respectively. The driving mechanism was revealed in terms of the pore water pressures, saturation, and displacement of the sliding zone. To account for water infiltration associated with the dynamic runout process of the landsliding, the sliding friction coefficient in DEA was examined. Based on the results, satisfactory agreement between the numerical analysis and landslide behavior was realized. In prefailure regime, the onset of landslide initiation was found through assessment of rapid change of source displacement (RCSD). The estimated seepage force was about 0.5 N at landslide initiation. In postfailure regime, the results demonstrate that water infiltration and transition in steepness play significant roles in the behavior of the dynamic runout process. The landsliding exhibited a maximum speed of 4.41 m/s and decelerated as it reached a more gentle slope. Overall, the study indicated that the coupling of FEA and DEA can be used to investigate the role of water infiltration and provide useful insights. The approach can be further applied for studies on many other rainfall-induced geohazards to disclose the role of water infiltration with the prefailure and postfailure characteristics.