NMC Group Research Articles

Tumoral inflammatory infiltrate does not predict metastases in thin primary cutaneous melanomas

BackgroundIn cutaneous melanomas in general, tumor inflammatory infiltrate (TII) can protect against distant metastases, but there is no consensus when only thin primary cutaneous melanomas (TPCM) are considered. ObjectiveTo investigate the presence of TII in TPCM and the relationship between TII and the occurrence of metastases. MethodsCase-control study including 50 patients with TPCM, 22 metastatic (MC group) and 28 non-metastatic (NMC group). The presence of TII was evaluated and, if present, qualified as mild, moderate or marked. ResultsThe mean age was 50.7 years in the MC and 56.2 years in the NMC group (p = 0.234), and the male sex predominated in the MC group (63.6%). The average Breslow thickness was higher in the MC when compared to that observed in the NMC (respectively 0.8 vs. 0.6 mm, p = 0.012). The presence of ulceration occurred in 22.7% of the MC and 17.9% of the NMC (p = 0.732). TII was present in all 50 TPCM, being marked or moderate in 67.9% of the NMC and 54.5% in the MC group (p = 0.503). In the multivariate analysis, the presence of moderate and marked TII had an Odds Ratio (OR) of 0.57 (95% Confidence Interval [CI]: 0.18‒1.8) and adjusted OR of 0.68 (95% CI 0.13‒3.99). Study limitationsSmall sample size. ConclusionsTII was present in all TPCM (with and without metastases), and it was not possible to demonstrate a protective effect of TII against the appearance of metastases.

Traumatic maxillofacial injuries: Patterns, outcomes, and long-term follow-up of a military cohort.

Maxillofacial trauma poses a distinct challenge on the modern battlefield, and data on its long-term implications are scarce. The aim of this study was to investigate maxillofacial injury characteristics, outcomes, and complications along the continuum of care among hospitalized military personnel from the pre-hospital setting through long-term rehabilitation. A registry-based study was undertaken of three national trauma and rehabilitation registries: The Israel Defense Forces Trauma Registry (IDF-TR), which records pre-hospital data. The Israeli National Trauma Registry for in-hospital data and the Israel Ministry of Defense Rehabilitation Department (MOD-RD) registry contain long-term disability data. The cohort comprised IDF soldiers who suffered maxillofacial injuries between 1997 and 2020. A total of 672 patients with maxillofacial injuries were included in the study, and 6.4% of all trauma admissions were related to maxillofacial injuries. Of these, 366 (54%) were injured in non-military (NMC) circumstances, and 306 (46%) were wounded in military circumstances (MC). The mechanisms of injury were mainly traffic-related among the NMC group compared with an explosion in the MC group. Maxillofacial fractures were frequently associated with traumatic brain injuries with higher rates in the NMC group than in the MC group (55% vs. 30%, p < .001). In a multivariate analysis, zygomatic and orbital fractures were associated with higher odds of concomitant head injury. The most common categories of long-term disability included central nervous system disorders, skull injuries, epilepsy, hearing impairment, ophthalmologic conditions, and post-traumatic stress disorder. Maxillofacial injuries are often associated with concomitant traumatic brain injury. Long-term disabilities associated with these injuries included the central nervous system, hearing, ophthalmologic impairments, and post-traumatic stress disorder.

The reproductive endocrine feature and conception outcome of women with unknown etiological menstrual cycle (36–45 days) with long follicular phase

Objective To explore the reproductive endocrine feature and conception outcome of women with unknown etiological long menstrual cycle (LMC) (36–45 days) with long follicular phase. Methods In the cohort study, we included 80 women with unknown etiological long menstrual cycle of biphasic basal body temperature (BBT) lasting for 36–45 days and 87 controls with normal cycle of biphasic BBT into LMC group and NMC group, respectively. Serum hormone levels, fasting glucose, and insulin of participants were tested, and ovulation was observed by ultrasound. The conception outcome was followed up within 12 menstrual cycles. Results In the LMC group, the rate of abnormality of HOMA-insulin resistance index (40.0% vs. 20.7%, p < .01), luteal phase defect (30.9% vs. 13.8%, p < .05) and abnormality of FSH/LH ratio (15.6% vs. 5.7%, p < .05) were all significantly higher, but the serum estradiol level on the day before ovulation (261.10 pg/mL vs. 320.26 pg/mL, p < .01) was lower. The rate of poor ovulation quality (31.3% vs.15.4%, p < .05) in the LMC group was significantly higher than the NMC group. In the LMC group, the natural conception rate within 12 menstrual cycles was lower (41.9% vs. 66.2%, p < .01), whereas the spontaneous abortion rate in early pregnancy (29.0% vs. 9.8%, p < .05) and the conversion rate (21.6% vs. 5.2%, p < .01) to anovulation within 12 cycles were significantly higher. Conclusions Women with unknown etiological menstrual cycle (36–45 days) with long follicular phase have greater endocrine abnormality and higher risk of spontaneous abortion, infertility, and conversion to anovulation. Moderate early intervention may be advisable for these women, especially those who wish to get pregnant.

Neurodevelopmental toxicity of alumina nanoparticles to zebrafish larvae: Toxic effects of particle sizes and ions

The aim of this study was to explore the mechanism of neurodevelopmental toxicity of alumina nanoparticles (AlNPs) on zebrafish larvae, specifically, the toxic effects of AlNPs of different particle sizes and of dissolved aluminum ions. AlNPs with sizes of 13 nm (13 nm-Al) and 50 nm (50 nm-Al) were used as the main research objects; while nanocarbon particles with sizes of 13 nm (13 nm-C) and 50 nm (50 nm-C) as particle-size controls; and an aluminum chloride solution (Al3+) as an ion control. Zebrafish embryos were exposed to different treatments from 6 h post-fertilization (hpf) to 168 hpf. Deformities were observed at different time points. Neurodevelopmental behavior tests were carried out, and oxidative stress responses and transcriptional alterations in autophagy-related genes were assessed. Malformations occurred in the 13 nm-Al, 50 nm-Al, and Al3+ treated groups at different developmental stages of zebrafish larval, but no malformations were observed in the 13 nm-C or 50 nm-C groups. In addition, the average speed, distance travelled and thigmotaxis in zebrafish larvae decreased in the AlNPs treated group, and the effects were related to the particle sizes. Furthermore, increases in the oxidative stress response and autophagy-related genes expression were also related to the particle sizes of AlNPs as well. In conclusion, the mechanism underlying the neurodevelopmental toxicity of AlNPs on zebrafish larvae mainly depended on the size of the nanoparticles, and dissolved Al3+ also contributes to the toxic effects.

Modic changes are associated with activation of intense inflammatory and host defense response pathways – molecular insights from proteomic analysis of human intervertebral discs

Patients with modic changes (MC) form a distinct clinical subset with reports of higher intensity of pain, poor clinical and surgical outcomes and higher incidence of recurrence. MC also is an independent risk factor for increased post-operative surgical site infection. This study aimed to investigate the biological changes at molecular level, in discs with MCs. We also aim to identify biological biomarkers and potential targets for molecular therapy. Experimental analysis MATERIALS AND METHODS: Nucleus pulposus (NP) from 24 patients undergoing microdiscectomy for disc herniation [14 discs with MC and 10 without modic changes (NMC)] were procured. The overall expression of proteins, biological processes, protein-protein and metabolite interactions were analysed and compared. Host defense response proteins (HDRPs) and immunological pathways activated in patients with MC were documented and analysed. Label-free proteomic approach with stringent filters revealed a total of 208 proteins in MC and 193 in NMC groups. 45 proteins were specific to MC; 30 to NMC and 163 common to both. Downregulated proteins in MC belonged to components of extracellular matrix such as collagens (COL- 6A1, 6A2, 6A3, 11A1, 12A1, and 20A1), and proteoglycans (versican (VCAN), and biglycan (BGN)). Inflammatory molecules [plasminogen (PLG), angiogenin (ANG), fibroblast growth factor-binding protein 2 (FGFBP2), tetranectin (CLEC3B), cartilage acidic protein 1(CRTAC1), kininogen (KNG-1), chitinase-3-like protein 2 (CHI3L2), and ferritin (FTL) were expressed only in the MC group. The significantly altered pathways in MC included Fc Fragment of IgG Receptor IIIa (FCGR3A)-mediated phagocytosis, regulation of Toll-like receptors (TLR) by endogenous ligand, neutrophil and platelet degranulation. 50 HDRPs were identified in the study, 14 of which were specific to MC and included acute phase reactants, antimicrobial peptides, complement cascade proteins, inflammatory molecule and stress response proteins. Metabolite-protein interaction analysis revealed a significant interaction between 19 proteins, specifically involving ubiquitin mediating proteasome degradative pathway and an association with the metabolite-glutamic acid in the MC group. Accumulation of glutamic acid in MC discs was confirmed by quantitative amino acid analysis using High-performance liquid chromatography. Our study confirms that MC represents an intense inflammatory status and activation of host defense response and immunological pathways. Downstream effects leading to ubiquitin mediated proteasomal degradation of ECM proteins and the resulting metabolites such as glutamic acid could cause excessive pain and needs further investigation. We have documented the expression of inflammatory molecules, immune mechanisms and host defense response proteins which throw molecular insights into the pathological mechanisms of MC. Further, ubiquitin mediated proteasomal degradation and accumulation of glutamate in discs with MC might serve as targets for molecular therapy.

Nicotine and modafinil combination protects against the neurotoxicity induced by 3,4-Methylenedioxymethamphetamine in hippocampal neurons of male rats

MDMA (3,4-Methylenedioxymethamphetamine) is a common recreational drug of abuse which causes neurodegeneration. Nicotine and modafinil provide antioxidant and neuroprotective properties and may be beneficial in the management of MDMA-induced neurotoxicity. The purpose of this study was to characterize how acute and chronic administration of nicotine and/or modafinil exert protective effects against the MDMA-induced impaired cognitive performance, oxidative stress, and neuronal loss. Adult male rats were divided into three groups, namely control, MDMA and treatment (modafinil and/or nicotine). MDMA (10 mg/kg) was administered intraperitoneally during a three-week schedule (two times/day for two consecutive days/week). The treated-groups were classified based on the acute or chronic status of treatment. In the groups which underwent acute treatments, nicotine (0.5 mg/kg) and/or modafinil (100 mg/kg) were injected just prior to the MDMA administration (acute nicotine (NA), acute modafinil (MA), and acute nicotine and modafinil (NMA)). In the rats which received chronic treatments, nicotine (0.5 mg/kg) and/or modafinil (100 mg/kg) were injected every day during the three week-schedule administration of MDMA (chronic nicotine (NC), chronic modafinil (MC), and chronic nicotine and modafinil (NMC)). Learning and memory performance, as well as avoidance response, were assessed by Morris water maze and Shuttle box, respectively. Our findings indicate enhanced learning and memory and avoidance response in the NMC group. By TUNEL test and Cresyl Violet staining we evaluated neuronal loss and apoptosis in the hippocampal CA1 and found increased neuronal viability in the NMC group. On the other hand, chronic administration of modafinil and nicotine significantly down-regulated the caspase 3 and up-regulated both BDNF and TrkB levels in the MDMA-received rats. The serum levels of glutathione peroxidase (GPx) and total antioxidant capacity (TAC) were evaluated and we found that the alterations of serum levels of GPx and TAC were considerably prevented in the NMC group. The overall results indicate that nicotine and modafinil co-administration rescued brain from MDMA-induced neurotoxicity. We suggest that nicotine and modafinil combination therapy could be considered as a possible treatment to reduce the neurological disorders induced by MDMA.

Src‐phosphorylation at the α1‐Na/K‐ATPase is Associated with Microbiota Community Changes in Diet‐Induced NASH in the Murine

Background Obesity is a rising epidemic, leading to the increased prevalence of NAFLD/NASH (Non-alcoholic Fatty Liver Disease/Non-alcoholic steatohepatitis) that affects 25% of the US population. Gut microbiota has been implicated in NASH for its metabolic and inflammatory alterations, while the inhibition of Src phosphorylation (Src-p) signaling at the α1-Na/K-ATPase has been shown to attenuate established NASH. This study aimed to determine the effects of Src-p inhibition on gut microbiota communities and its association with NASH progression. Methods DNA from the terminal ileum microbiota habitat was obtained from rodents with diet induced NASH and amplified by PCR to develop DNA bacterial phylogenic sequence analysis of wild type and treated animals at 12, 24 and 48 weeks. For animals at 24 weeks, Src-p inhibition was correlated with liver morphological changes, intestinal CD4+/CD8+ ratio, and liver macrophage CD14+ expression. Differences among groups were evaluated by ANOVA/t-test and Principal Component Analysis (PCA). Results Microbiota communities varied significantly at all time points (12, 24 and 48 weeks, p<0.01, PCA), with an increase of Verrucomicrobia and a decrease of Bacteroidetes and Firmicutes in the HFD vs. NMC group. Microbiota communities regressed to their wild type state at 24 weeks through Src-p inhibition (p<0.05). This Src-p inhibited microbiota phenotype was associated with a decrease in liver inflammation and senescence, as well as associated with lower ileum CD4+ & CD8+ T cell levels and higher liver CD14+ expression (p<0.05). Conclusions Intestinal microbiota changes in NASH are significantly associated with Src-phosphorylation at the α1-Na/K-ATPase. Src-p inhibition returned microbiota communities to their wild type, concomitantly observed with amelioration of liver inflammation, cellular senescence, and both adaptive and innate immune responses in the gut and liver.

Src-phosphorylation at the α1-Na/K-ATPase Modulates Liver Cell Senescence and Microbiota Communuty Changes on Diet Induced NASH in the Rodent

Background: The global incidence of chronic liver disease and its sequels ESLD and HCC are increasing due to obesity and increase in life expectancy. We hypothesized Western diet accelerates aging cell processes inducing liver cell portfolio to senescence/apoptotic activity with altered metabolic cycles and disturbed gut-microbiota communities mainly though a Src pathway. Methods: Mice were exposed to NMC or HFD. Livers and plasma were collected at weeks 12, 24 and 48. Body compartments were determined by MRI spectroscopy. The terminal ileum (TI) and its microbiota were collected. Total DNA was extracted from contents of ileum and microbial community profiling was achieved by sequencing 16S rRNA v3-v4 hypervariable regions. Quantitative protein expression of Tp53, mTOR1, Src, SIRT7, FOX01, Grb2 were determined by Western Blots. Principal component analyses (PCA) was conducted. Results: TBW increases with aging manly due to an increase in the fat compartment with decreased lean mass and total body water (p< 005); changes that correlated with an increased proportion of liver cells in senescence/apoptosis (p< 0.05). Morphological changes correlated with Src peak gene expression. A significant increase in Verrucomicrobia was observed in the HFD group when compared to the NMC group (p< 0.05). Additionally, a significant decrease in Bacteroidetes was noted (p< 0.05). pNaKtide, a 33 amino-peptide that blocks the activation of Src at the α1-Na/K-ATPase subunit abrogated metabolic, genetic and morphologic changes establishing a wild phenotype. Conclusions: Blockage of the α1-Na/K-ATPase//Src amplification loop restored both physiological liver cell aging, and wild type gut-microbiota communities.

Failure mode analysis of lithium ion batteries operated for low Earth orbit CubeSat applications

Abstract Three types of 18-65 cylindrical lithium-ion cells with different positive active materials (NCA – nickel cobalt aluminium, NMC – nickel manganese cobalt, LFP – lithium iron phosphate), negative active material graphite average particle sizes (2 – 30 µm) and electrode designs (high power, high energy) were tested using an accelerated low earth orbit (LEO) CubeSat power profile cycle. Each design yields a unique energy density, power capability and cycle life. Each cell type was tested in a 3P group configuration at 10°C in atmospheric pressure (101 kPa-abs) and under vacuum (0.2 kPa-abs). Cell groups were operated in their respective pressure condition until they failed to successfully execute the accelerated LEO cycle. In atmospheric pressure and vacuum, both NMC groups failed due to internal resistance (IR) growth. The atmospheric pressure NCA group failed due to excessive internal gas build-up triggering the current interrupt device (CID) to electrically disconnect. The NCA group in vacuum failed from both IR growth and capacity degradation. The LFP groups both in atmospheric pressure and vacuum have completed approximately 5078 LEO cycles or 2800 equivalent cycles of initial measured coulombic capacity and are still operational with 19% and 21% capacity degradation from their initial measured coulombic capacity, respectively.

Is the bone fusion affected by Modic-2 changes in single-level anterior cervical discectomy and fusion?

To explore the impact of Modic changes (MCs) on bone fusion after single-level anterior cervical discectomy and fusion (ACDF) with a zero-profile implant (the Zero-P implant system).From November 2014 to November 2017, a total of 116 patients who underwent single-level ACDF with the Zero-P implant were divided into two groups according to MRI showing type 2 MCs (MC2) or no MCs (i.e., the MC2 group and the NMC group, respectively). A total of 92 (79.3%) patients were classified into the NMC group, and 24 (20.7%) patients were classified into the MC2 group. The clinical outcomes and fusion rates were retrospectively evaluated between the 2 groups preoperatively and postoperatively at 3, 6, and 12 months, and the final follow-up.The Japanese Orthopedic Association (JOA) scores and the visual analogue scale (VAS) scores of neck pain were significantly improved compared to the preoperative scores in both the NMC and MC2 groups (P < .05). However, there were no differences in JOA or VAS scores between the 2 groups (P > .05). The fusion rates of the NMC and MC2 groups at 3, 6, and 12 months postoperatively, and the final follow-up were 33.7% and 12.5%, 77.2% and 54.2%, 89.1% and 87.5%, and 97.8% and 95.8%, respectively. The fusion rates were significantly lower at 3 and 6 months after surgery in the MC2 group than in the NMC group (P < .05).The presence of MC2 did not affect the clinical outcome but delayed the fusion time following ACDF with the Zero-P implant system.Level of Evidence is Level 3.

Impact of postoperative major complications on long-term survival after radical resection of gastric cancer

BackgroundThis study was designed to evaluate the impact of postoperative major complications on long-term survival following curative gastrectomy.MethodsThis retrospective study included 239 patients with gastric cancer undergoing gastrectomy at the Beijing Cancer Hospital from February 2012 to January 2013. Survival curves were compared between patients with major complications (mC group) and those without major complications (NmC group). Multivariate analysis was conducted to identify independent prognostic factors.ResultsPostoperative complication and mortality rates were 24.7 and 0.8%, respectively. The severity of complications was graded in accordance with the Clavien–Dindo classification. The incidence of minor complications (grades I-II) and major complications (grades III–V) was 9.2 and 15.5%, respectively. The 3-year overall survival (OS) and disease-free survival (DFS) rates were better in the NmC group than in the mC group (p = 0.014, p = 0.013). Multivariate analysis identified major complications as an independent prognostic factor for OS and DFS. After stratification by pathological stage, this trend was also observed in stage II patients.ConclusionsPostoperative major complications adversely affect OS and DFS. The prevention and early diagnosis of complications are essential to minimize the negative effects of complications on surgical safety and long-term patient survival.

Intervention for Feeding Difficulties in Children With a Complex Medical History: A Randomized Clinical Trial.

This study aimed to compare outcomes of different multidisciplinary feeding therapy approaches in children with feeding difficulties. Children aged 2 to 6 years with feeding difficulties and a medically complex history (MC) were recruited. Children with feeding difficulties and a nonmedically complex history (NMC) were included as a comparison group. Participants attended a clinical assessment, and eligible participants were randomized to receive targeted feeding intervention incorporating either operant conditioning or systematic desensitization. Parents could elect to receive intervention in an intensive (10 sessions in a week) or weekly (10 sessions during 10 weeks) format. Both groups received immersive parent training. A review was completed 3 months post-intervention. In total, 98 participants were eligible to participate (MC, n = 43; NMC, n = 55). Data from 20 children from the MC group (47%) and 41 children from the NMC group (75%) were included in the final analysis. Clinically significant improvements were observed following both arms of therapy, consistent with previous research. Parents of children in the MC arm were significantly more likely to elect for intensive intervention than weekly (MC = 12/20, 60%; 12/41, 29%; P = 0.02). Both therapy protocols were considered clinically effective. The difference in attrition rates between the etiological groups suggests primary differences in how service delivery should be managed. Progress for the medically complex child may be slower while medical issues are stabilized, or while the focus for parents shifts to other developmental areas. In planning services for a medically complex group, therefore, it is essential that consideration be given to medical and family needs.

Effects of Non-Uniform Temperature on In-Situ Current Distribution and Non-Uniform State of Charge Measurements for LiFePO4 and LiNiMnCoO2 Cells

Understanding internal state non-uniformity occurring across the electrodes in large-format Lithium-ion batteries, and among parallel-connected cells, is a critical part of the cell and battery module design process. Two five-cell parallel groups were tested using LiFePO4/C6 (LFP), and LiNiMnCoO2/C6 (NMC) chemistries. Pulse and full-capacity discharges were performed at various States of Charge (SOC), C-rates, average temperatures, and levels of temperature non-uniformity. In pulse testing, the current non-uniformity was lower for the LFP group compared to the NMC group. The hottest cell in the LFP group produced up to 40% more current than average, while this was up to 80% for NMC. Conversely, under charge depleting conditions the NMC group experienced less current non-uniformity, and in certain cases provided a nearly uniform current distribution in the presence of non-uniform temperature. Higher temperature sensitivity in the impedance causes larger current non-uniformity under pulse conditions. However, due to the presence of non-uniform SOC in charge depletion conditions, the Open Circuit Voltage (OCV) versus SOC gradient plays a significant role in controlling the current distribution, where steeper OCV versus SOC minimizes the effect of the non-uniform impedance.

Current Distribution Measurements in Parallel-Connected Lithium-Ion Cylindrical Cells under Non-Uniform Temperature Conditions

Understanding internal state non-uniformity that occurs across the electrodes in large-format Lithium-ion batteries, and among parallel-connected cells, is a critical part of the cell and battery module design process. Two separate groups of parallel-connected 18650 cells were tested using LiFePO4/C6 (LFP), and LiNiMnCoO2/C6 (NMC) chemistries. Pulse and full-capacity discharges were performed at various States of Charge (SOC), C-rates, average temperatures, and levels of temperature non-uniformity. Current non-uniformity for the pulse testing was always lower for the LFP group compared to the NMC group. The hottest cell in the LFP group produced up to 40% more current than average, while this was up to 80% for NMC. Conversely, under charge depleting conditions the NMC group experienced less current non-uniformity, and in certain cases provided a nearly uniform current distribution in the presence of non-uniform temperature. The results indicate that higher temperature sensitivity in the impedance of a cell will cause larger current non-uniformity under pulse conditions. However, due to the presence of non-uniform SOC for charge depleting, the Open Circuit Voltage (OCV) versus SOC gradient plays a significant role in dictating the current distribution behavior, where steeper OCVs provide a corrective action that minimizes the effect of the non-uniform impedance.

Treinamento aeróbio não altera pressão arterial de mulheres menopausadas e com síndrome metabólica

Arterial Hypertension (AH) is an aggravating condition for Metabolic Syndrome (MS), as well as being aggravated by it. Menopause can make hypertension treatment more difficult, as it favors the worsening of MS components. Although there is evidence that exercise training reduces blood pressure, whether menopause and SM affect the exercise-induced benefits is yet to be elucidated. To compare the effects of aerobic training on blood pressure in non-menopausal and menopausal women with MS METHODS: A total of 44 women were recruited and divided into four groups: non-menopausal control (NMC: 39.5 ± 3.6 years, n = 11); menopausal control (MC: 54.9 ± 5.9 years, n = 12), non-menopausal aerobics (NMA: 43.1 ± 6.8 years, n = 11) and menopausal aerobics (MA: 52.1 ± 5 years, n = 10). The exercise groups performed aerobic training for three months, five times a week, at an intensity between 60% and 70% of heart rate reserve. The resting blood pressure and blood pressure response after 60 minutes of exercise were measured before and after the training period. The two-way ANOVA test was used, considering a p value < 0.05. The training program resulted in a decrease in abdominal fat, blood glucose and improved VO2 max. Compared to pre-intervention values, Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) did not change after training in NMC, MC, MA and NMA groups (p > 0.05). Three months of aerobic training improved MS components, but did not alter resting blood pressure or the BP response after an acute exercise session in women with MS.

Conditioning Intensity in Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Diffuse Large B-Cell Lymphoma (DLBCL)

Abstract 501Non-myeloablative (NMC) and reduced intensity (RIC) conditioning approaches rely primarily on a graft-vs-lymphoma (GVL) effect and aim at reducing transplant-related mortality (TRM) associated with myeloablative conditioning (MAC). We analyzed outcomes for 396 adults (228 male) receiving alloHCT for DLBCL following MAC (n=165), RIC (n=143) or NMC (n=88) regimens between 2000 and 2009 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Conditioning regimens were classified using consensus criteria. Engraftment, cumulative incidences of acute and chronic graft-vs-host disease (GvHD), TRM, progression and probabilities of progression-free (PFS) and overall survival (OS) were compared between MAC and NMC/RIC.Common MAC regimens were cyclophosphamide (CY) + total body irradiation (TBI) (54%) and busulfan (BU) + CY (23%). Common RIC regimens were fludarabine (Flu) with melphalan (44%) or BU (39%) and for NMC, Flu with CY (48%) and low dose TBI (33%). Practice patterns changed with declining use of MAC regimens after 2003 (> 66% of total being MAC pre-2003 and <33% after). Donors were HLA matched siblings in 40%, 26%, 30% of MAC, RIC and NMC recipients, respectively, with 67% overall receiving unrelated donor (URD) grafts. Significant (p <0.05) baseline differences between the cohorts included: RIC and NMC recipients were older (54% and 58% >50 yrs vs 39% for MAC), more likely to have received prior autoHCT (36% and 51% vs 18%), prior radiation and more prior chemotherapy regimens (55 and 70% vs 44% with >3 regimens) than those with MAC. Recipients of RIC and NMC were less likely to have chemotherapy resistant disease (30% and 26% vs. 42% for MAC); and had a longer median interval from diagnosis to alloHCT (median 27 and 36 mo vs. 17 mo).Day 100 engraftment was more frequent in RIC and NMC recipients (99% and 97% with ANC >500/cu.mm vs. 88% for MAC, p <0.001). Acute (43–44%) and chronic GvHD incidence (37–42% at 5 years) was similar across the groups. Outcomes are summarized in Table 1. TRM at day +100 and at 5 years was significantly higher for MAC compared with RIC and NMC groups (See Table 1). Lymphoma relapse/progression at 5 years was significantly lower for MAC vs. RIC and NMC but 5 year PFS and OS at 5-years did not differ significantly. In multivariable analysis, NMC (HR 0.58, p=0.026) and later year of alloHCT (HR 0.49, p<0.001) were associated with lower TRM while Karnofsky status <90 (HR 1.51, p=0.011), chemo-resistant relapse (HR 2.79, p<0.001) and URD (HR 2.32, p<0.001) were associated with higher TRM. Higher incidence of relapse/progression was associated with NMC (HR 2.14, p=0.003), non-receipt of rituximab prior to alloHCT (HR 1.69, p=0.008) and chemo-resistant disease (HR 2.06, p=0.006). Conditioning intensity did not impact OS and PFS.In selected patients with advanced DLBCL, allogeneic HCT can induce long-term PFS irrespective of the intensity of conditioning with a lower incidence of TRM with RIC and NMC regimens. Due to increased toxicity, the use of MAC regimens has been declining in recent years. However, the incidence of RIC/NMC, risk of relapse/progression was concordantly higher in the RIC/NMC recipients so that survival did not differ significantly between conditioning regimens. Further studies are needed to clarify optimal conditioning strategies for advanced DLBCL aiming to further reduce TRM.Table 1:ParameterIntensity of Conditioning (95% CI)p-valueMACRICNMCTRM @day +100 at 5 yrs32% (25–39%)24% (17–31%)17% (10–26%)0.02956% (48–64%)47% (38–56%)36% (26–46%)0.007Relapse @ 5 yrs26% (19–33%)38% (30–46%)40% (30–50%)0.031OS @ 5 yrs18% (12–25%)20% (13–29%)26% (17–36%)0.365PFS @ 5 yrs18% (12–24%)15% (9–23%)25% (16–34%)0.309 [Display omitted] Disclosures:Montoto:Genentech: Research Funding; Roche: Honoraria.

In Conversation With: Dr. B R Shetty, Chairman, NMC Group, UAE

In Conversation With: Dr. B R Shetty, Chairman, NMC Group, UAE

Evidence for charge symmetry violation in parton distributions

A comparison of the structure functions measured in neutrino and charged lepton deep inelastic scattering can be used to test basic properties of parton distribution functions such as charge symmetry. Recent data from the CCFR and NMC groups indicate a substantial discrepancy between F 2 ν and F 2 μ in the small-χ region. We show that neither nuclear corrections nor strange quark effects can account for the observed discrepancy. These results suggest that the nucleon sea exhibits surprisingly large charge symmetry violation.

On the universality of the x and A dependence of the EMC effect and its relation to parton distributions in nuclei

It is shown that the latest results from the NMC (CERN) and E665 (Fermilab) groups on F 2 a(x) F 2 d(x) obtained in the shadowing region bring new evidence of the universal A dependence of distortions made in a free-nucleon structure function by a nuclear medium. The observed universality implies that one can consider separately hard ( A ≤ 4) and soft ( A > 4) parton distribution distortions. Soft distortions, which result in differencies between the deep-inelastic scattering cross-sections for nuclei with masses A 1, A 2 ≥ 4, can be explained as a consequence of the nuclear density variation, independent of x in the range 0.001 ≤ x ≤ 0.7. It is found that nuclear shadowing begins at x 1 = 0.0615 ± 0.0024, independent of A, which is consistent with models that allow for three-parton recombination processes.

Gottfried and Bjorken sum rules: The role of vector diquarks

A quark-diquark model of the nucleon is considered and the value of the Gottfried sum ruleSG, recently measured by the NMC group and found to differ considerably from the quark parton model expectation,SG=1/3, is computed allowing for both elastic and inelastic contributions from the diquarks. This approach fails to reproduce the data, unless vector diquark contributions persist at very largeQ2 values, contrary to the usual assumptions. The Bjorken sum rule andSU(6) violations due to the quark-diquark structure of the nucleon are also briefly discussed.