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OBJECTIVE: This study examined pretreatment variables to predict outcome in two treatments for bulimia nervosa. METHOD: Patients were offered either 16 weeks of cognitive-behavioral therapy (CBT) or a self-treatment manual followed by up to 8 weeks of CBT (sequential group). Using complete data, stepwise regression analyses were performed. RESULTS: It was found that a longer duration of illness and lower binge frequency predicted a better outcome both at the end of treatment (p < .001) and at 18 months of follow-up (p < .005). In the sequential group, lower pretreatment binge frequency predicted better outcome at the end of treatment (p < .05) and at 18 months of follow-up (p < .05). In the CBT group, longer duration of illness predicted better outcome at the end of treatment (p < .02). DISCUSSION: It is concluded that (1) those with more frequent binging may require a more intense intervention and (2) those who have been ill longer may be more motivated to respond to treatment. [ABSTRACT FROM AUTHOR]

In a monopolistically competitive model with production externalities, where individuals voluntarily provide offsets which compensate for degradation of environmental quality caused by their income earning activities, this paper examines how an increase in the population size affects the equilibrium levels of environmental quality, offsets, and net contributions. Whether labor supply is institutionally constrained or not, as the population size increases, environmental quality decreases and converges to zero. However, since offsets increase and converge to the degradation rate of environmental quality, the carbon neutrality theorem holds: net contributions are zero. These results are independent of the specification of the utility function., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor immunity. Here, we report the first open-label, phase Ib clinical trial of a personalized neoantigen-based vaccine, NEO-PV-01, in combination with PD-1 blockade in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. This analysis of 82 patients demonstrated that the regimen was safe, with no treatment-related serious adverse events observed. De novo neoantigen-specific CD4 + and CD8 + T cell responses were observed post-vaccination in all of the patients. The vaccine-induced T cells had a cytotoxic phenotype and were capable of trafficking to the tumor and mediating cell killing. In addition, epitope spread to neoantigens not included in the vaccine was detected post-vaccination. These data support the safety and immunogenicity of this regimen in patients with advanced solid tumors (Clinicaltrials.gov: NCT02897765)., Competing Interests: Declaration of Interests P.A.O.: research funding paid to the institution—Bristol-Myers Squibb, Merck, AstraZeneca, Celldex, CytomX, GlaxoSmithKline, ARMO Biosciences, Neon Therapeutics; consultant—Array, Bristol-Myers Squibb, Merck, Genentech, Pfizer, Novartis, Neon Therapeutics, CytomX, Celldex. S.H.-L.: consultant—Amgen, Bristol-Myers Squibb, Genmab, Xencor; research support—Bristol-Myers Squibb, Merck, and Vaccinex. B.C.: member of the speakers’ bureaus for Regeneron and Sanofi. R.G.: advisory board member—Achilles; consultant—Horizon Pharma (spouse), GenePlus. A.N.: research funding from NCI, EMD Serono, MedImmune, Healios Oncology Nutrition, Atterocor, Amplimmune, ARMO BioSciences, Eli Lilly, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol-Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Kymab, PsiOxus, and Immune Deficiency Foundation (spouse); advisory board member—CytomX Therapeutics, Novartis, Kymab, and Genome; travel and accommodation expense—ARMO BioSciences. N.B.: scientific advisory board member—Checkpoint Sciences, Curevac, Primevax, Novartis, Avidea, BI, Rome Therapeutics, Neon Therapeutics, Roche, and Genentech. Extramural member of the Parker Institute for Cancer Immunotherapy K.M.: advisory boards or consultant—Nektar, ImaginAb, Neoleukin, and Akrevia; DSMB—IOvance. M.M.A.: research grants—Genentech, Bristol-Myers Squibb, AstraZeneca, Lilly; consultant—Genentech, Bristol-Myers Squibb, AstraZeneca, Merck, Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, Gritstone, and Neon Therapeutics M.D.H.: research funding—Bristol-Myers Squibb; consultant—Merck, Bristol-Myers Squibb, AstraZeneca, Genentech/Roche, Nektar, Syndax, Mirati, Blueprint, Immunai, and Shattuck Labs; travel support/honoraria—AstraZeneca, Eli Lilly, Merck, and Bristol-Myers Squibb; and a patent has been filed by MSK related to the use of tumor mutation burden to predict the response to immunotherapy (PCT/US2015/062208), which has received licensing fees from PGDx. J.J.L.: honoraria/consultant—Pfizer, C4 Therapeutics, Nuvalent, and Genentech; institutional research funding—Neon, Hengrui Therapeutics, Turning Point Therapeutics, and Novartis; travel fees—Pfizer; CME funding—OncLive. T.F.: research funding—Janssen; research funding to the institute—Seattle Genetics, Incyte, Bristol-Myers Squibb, Neon Therapeutics, and Roche/Genentech. R.B.G.: board of directors—Alkermes plc and Infinity Pharmaceuticals; scientific advisory board—Leap Therapeutics; stockholder and employee—Neon Therapeutics/BioNTech US. Stockholder and either current or past employees of Neon Therapeutics/BioNTech US: M.E.B., K.N.B., T.E.S., V.K., S.J.T., R.B., R.R.C., B.T., J.S., A.P., D.H., D.B., Y.S.T., J.Z.D., Y.W., Y.H., Z.H., A.W., L.D.C., M.A.M., K.M., J.G., Z.S.K., M.S.R., M.D., E.F., and L.S., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors, including those targeting programmed cell death protein 1 (PD-1), are reshaping cancer therapeutic strategies. Evidence suggests, however, that tumor response and patient survival are determined by tumor programmed death ligand 1 (PD-L1) expression. We hypothesized that preconditioning of the tumor immune microenvironment using targeted, virus-mediated interferon (IFN) stimulation would up-regulate tumor PD-L1 protein expression and increase cytotoxic T cell infiltration, improving the efficacy of subsequent checkpoint blockade. Oncolytic viruses (OVs) represent a promising form of cancer immunotherapy. For brain tumors, almost all studies to date have used direct intralesional injection of OV, because of the largely untested belief that intravenous administration will not deliver virus to this site. We show, in a window-of-opportunity clinical study, that intravenous infusion of oncolytic human Orthoreovirus (referred to herein as reovirus) leads to infection of tumor cells subsequently resected as part of standard clinical care, both in high-grade glioma and in brain metastases, and increases cytotoxic T cell tumor infiltration relative to patients not treated with virus. We further show that reovirus up-regulates IFN-regulated gene expression, as well as the PD-1/PD-L1 axis in tumors, via an IFN-mediated mechanism. Finally, we show that addition of PD-1 blockade to reovirus enhances systemic therapy in a preclinical glioma model. These results support the development of combined systemic immunovirotherapy strategies for the treatment of both primary and secondary tumors in the brain., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Several prognostic indices have been devised to optimize patient selection for phase 1 oncology trials with no consensus as to the optimal score and none qualifying as a marker of treatment response., Methods: Multivariate predictors of overall survival (OS) were tested on 118 referred patients to develop the Hammersmith Score (HS). The score's ability to predict OS, progression-free survival (PFS), and 90-day mortality (90DM) was compared with other prognostic indices. Changes in HS were recalculated during treatment., Results: Albumin<35 g/L, lactate dehydrogenase>450 U/L, and sodium<135 mmol/L emerged as independent prognostic factors. These were used with equal weighting to devise the HS, a compound prognostic index ranging from 0 to 3. High (HS=2-3) score predicted worse OS (hazard ratio [HR]=6.5, P<.001), PFS (HR=2.8, P=.01), and 90DM (OR=9.0, P<.001). HS was a more accurate multivariate predictor of OS (HR=6.4, P<.001, C-index=0.72), PFS (HR=2.7, P=.03), and 90DM (area under the ROC curve 0.703) compared with other scores. Worsening of the HS during treatment predicted for shorter OS (P<.001). HS retained prognostic and predictive ability following external validation., Conclusions: HS is a simple, validated index to optimize patient selection and predict survival benefit from phase 1 oncology treatments. Prospective validation is ongoing., (© 2013 American Cancer Society.)

Background: Adequate organ function and good performance status (PS) are common eligibility criteria for phase I trials. As inflammation is pathogenic and prognostic in cancer we investigated the prognostic performance of inflammation-based indices including the neutrophil (NLR) and platelet to lymphocyte ratio (PLR)., Methods: We studied inflammatory scores in 118 unselected referrals. NLR normalization was recalculated at disease reassessment. Each variable was assessed for progression-free (PFS) and overall survival (OS) on uni- and multivariate analyses and tested for 90 days survival (90DS) prediction using receiving operator curves (ROC)., Results: We included 118 patients with median OS 4.4 months, 23% PS>1. LDH≥450 and NLR≥5 were multivariate predictors of OS (p<0.001). NLR normalization predicted for longer OS (p<0.001) and PFS (p<0.05). PS and NLR ranked as most accurate predictors of both 90DS with area under ROC values of 0.66 and 0.64, and OS with c-score of 0.69 and 0.60. The combination of NLR+PS increased prognostic accuracy to 0.72. The NLR was externally validated in a cohort of 126 subjects., Conclusions: We identified the NLR as a validated and objective index to improve patient selection for experimental therapies, with its normalization following treatment predicting for a survival benefit of 7 months. Prospective validation of the NLR is warranted.

A nine-month in situ bioremediation study was conducted in Makua Military Reservation (MMR) in Oahu, Hawaii (USA) to evaluate the potential of molasses to enhance biodegradation of royal demolition explosive (RDX) and high-melting explosive (HMX) contaminated soil below the root zone. MMR has been in operation since the 1940's resulting in subsurface contamination that in some locations exceeds USEPA preliminary remediation goals for these chemicals. A molasses-water mixture (1 : 40 dilution) was applied to a treatment plot and clean water was applied to a control plot via seven flood irrigation events. Pore water samples were collected from 12 lysimeters installed at different depths in 3 boreholes in each test plot. The difference in mean concentrations of RDX in pore water samples from the two test plots was very highly significant (p < 0.001). The concentrations differences with depth were also very highly significant (p < 0.001) and degradation was greatly enhanced at depths from 5 to 13.5 ft. biodegradation was modeled as first order and the rate constant was 0.063 per day at 5 ft and decreased to 0.023 per day at 11 ft to 13.5 ft depth. Enhanced biodegradation of HMX was also observed in molasses treated plot samples but only at a depth of 5 ft. The difference in mean TOC concentration (surrogate for molasses) was highly significant with depth (p = 0.003) and very highly significant with treatment (p < 0.001). Mean total nitrogen concentrations also differed significantly with treatment (p < 0.001) and depth (p = 0.059). The molasses water mixture had a similar infiltration rate to that of plain water (average 4.12 ft per day) and reached the deepest sensor (31 ft) within 5 days of application. Most of the molasses was consumed by soil microorganisms by about 13.5 feet below ground surface and treatment of deeper depths may require greater molasses concentrations and/or more frequent flood irrigation. Use of the bioremediation method described herein could allow the sustainable use of live fire training ranges by enhancing biodegradation of explosives in situ and preventing them from migrating to through the vadose zone to underlying ground water and off-site.

A 15-week treatability study was conducted in a greenhouse to evaluate the potential effects of molasses on the bioremediation and phytoremediation potential of Guinea Grass (Panicum maximum) for treating energetic contaminated soil from the open burn/open detonation area of the Makua Military Reservation, Oahu, HI (USA). The energetics in the soil were royal demolition explosive (RDX) and high-melting explosive (HMX). Among the 6 treatments employed in this study, enhanced removal of RDX was observed from treatments that received molasses and went to completion. The RDX degradation rates in treatments with molasses diluted 1:20 and 1:40 were comparable suggesting that the lower dose worked as well as the higher dose. Treatments without molasses degraded RDX slowly and residuals remained after 15 weeks. The bacterial densities in molasses-treated units were much greater than those without molasses. Phytoremediation alone seems to have little effect on RDX disappearance. For HMX, neither bioremediation nor phytoremediation was found to be useful in reducing the concentration within the experimental period. The concentrations of nitrogen and phosphorous in the soil did not change significantly during the experiment, however, a slight increase in soil pH was observed in all treatments. The study showed that irrigating with diluted molasses is effective at enhancing RDX degradation mainly in the root zone and just below it. The long term sustainability of active training ranges can be enhanced by bioremediation using molasses treatments to prevent RDX deposited by on-going operations from migrating through the soil to groundwater and off-site., (Copyright © 2012 Elsevier B.V. All rights reserved.)

An investigation was carried out to identify the class characteristics of Polish people writing in English and to specifically identify those characteristics that separate Polish handwriting from English handwriting. In the first stage, 40 Polish and 40 English handwriting samples were collected and systematically examined. In total, 31 features were identified that occurred in ≥25% of the Polish handwriting samples and therefore considered class characteristics. Of these, chi-square analyses identified 21 class characteristics that occurred significantly more in Polish compared to English handwriting. Twenty-one of the class characteristics in the Polish handwriting had similar constructions to the copybook pattern thus supporting the theory that class characteristics frequently stem from the taught writing system. In the second stage, an algorithm was developed using seventeen of the class characteristics that successfully discriminated between a further 13 Polish and 12 English handwriting samples., (© 2010 American Academy of Forensic Sciences.)

Background: There is controversy as to whether PTSD can develop following a brain injury with a loss of consciousness. However, no studies have specifically examined the influence of the memories that the individuals may or may not have on the development of symptoms., Aims: To consider how amnesia for the traumatic event effects the development and profile of traumatic stress symptoms., Method: Fifteen hundred case records from an Accident and Emergency Unit were screened to identify 371 individuals with traumatic brain injury who were sent questionnaires by post. The 53 subsequent valid responses yielded three groups: those with no memory (n = 14), untraumatic memories (n = 13) and traumatic memories (n = 26) of the index event. The IES-R was used as a screening measure followed by a structured interview (CAPS-DX) to determine caseness and provide details of symptom profile., Results: Groups with no memories or traumatic memories of the index event reported higher levels of psychological distress than the group with untraumatic memories. Ratings of PTSD symptoms were less severe in the no memory groups compared to those with traumatic memories., Conclusions: Psychological distress was associated with having traumatic or no memories of an index event. Amnesia for the event did not protect against PTSD; however, it does appear to protect against the severity and presence of specific intrusive symptoms.

Rat monoclonal anti-idiotype antibodies (mAb2) were raised against two mouse monoclonal antibodies (mAb1), 1D10 and 2A6, with specificity for the M-like protein of Streptococcus equi. The capacity of the mAb2 to inhibit the binding between the corresponding mouse mAb1 against which the mAb2 were raised and the M-like protein was investigated in an inhibition EIA. One of the ten mAb2 examined, namely 5D1 (anti-mAb1 1D10), was able to inhibit this binding. The mAb2 5D1 bound to the mAb1 1D10 in such a way as to completely inhibit the subsequent binding of the M-like protein antigen to the paratope of the mAb1 1D10. The mAb2 5D1 is likely to represent a true image of the M-like protein antigen and may thus be described as an Ab2 beta anti-idiotype antibody.

We have developed an in vivo passive transfer assay using mice to identify monoclonal antibodies (mAbs) which offer protection against Streptococcus equi infection. The assay was developed using serum antibodies collected from horses convalescing from strangles. In this study, we show that a preparation of M-like protein, acid-extracted from S. equi, affords 80% protection to mice immunized with it. A number of mouse mAbs directed against a preparation of M-like protein were then assessed for their ability to passively protect mice against challenge with a lethal dose of the bacteria. Two mAbs, 1D10 and 2A6, were shown to be highly protective. It was also demonstrated, by means of a competitive enzyme immunoassay, that these mAbs recognized different epitopes in the preparation. Examination of a dose-response curve for mAbs 1D10 and 2A6 revealed that optimal levels of protection were achieved using 1 mg of either 1D10 or 2A6, or 0.5 mg 1D10 and 0.5 mg 2A6 given together. Immunological reactivity of these mAbs with a preparation of M-like protein showed that the antigens they recognized were comparable in size to some of the antigens recognized by convalescent horse serum antibodies. The role of immunoglobulin isotype in conferring protection is discussed.