On the separation between baryonic and dark matter: evidence for phantom dark matter?

The recent years have seen combined measurements of X-ray and (weak) lensing contours for colliding galaxy clusters such as, for instance, the famous "Bullet" cluster. These observations have revealed offsets in the peaks of the baryonic and (dominant) gravitational matter component of order ~(100-200) kpc. Such discrepancies are difficult to explain using modified theories for gravity other than dark matter. Or are they not? Here we use the concept of "phantom dark matter" that is based upon a Newtonian interpretation of the MONDian gravitational potential. We show that this idea is in fact capable of producing substantial offsets in idealistic density configurations, involving a uniform external field. However, when analysed in a MONDian cosmological framework we deduce that the size (and probablity) of the effect is too small to explain the observed offsets found in the most recent observations, at least in the simplest incarnation of phantom dark matter as discussed here. The lensing centers in merging galaxy clusters are likely very close to the centers of true mass even in a MONDian cosmology. This gives the support to the idea that neutrino-like non-collisional matter might be responsible for the observed offsets of lensing and X-ray peaks.Comment: 6 pages, 5 figures, accepted for publication in Ap

The Effect of Cosmological Background Dynamics on the Spherical Collapse in MOND

The effect of background dynamics of the universe on formation of large scale structures in the framework of Modified Newtonian Dynamics (MOND) is investigated. A spherical collapse model is used for modeling the formation of the structures. This study is done in two extreme cases: ({\it i}) assuming a universe with a low-density baryonic matter without any cold dark matter and dark energy; ({\it ii}) a dark energy dominated universe with baryonic matter, without cold dark matter. We show that for the case ({\it ii}) the structures virialize at lower redshifts with larger radii compared to the low-density background universe. The dark energy slow downs the collapse of the structures. We show that our results are compatible with recent simulations of the structure formation in MOND.Comment: 16 pages, 4 Figures, accepted by New Astronom

Management of diarrhea in patients with HER2-positive breast cancer treated with neratinib: A case series and summary of the literature

INTRODUCTION: Neratinib and neratinib-based combinations have demonstrated efficacy for treatment of human epidermal growth factor receptor 2-positive (HER2+) early-stage and metastatic breast cancers. However, diarrhea has been reported as a common adverse event leading to neratinib discontinuation. Results from the CONTROL trial suggest that proactive diarrhea management with antidiarrheal prophylaxis or dose escalation of neratinib from a lower starting dose to the full FDA-approved dose of 240 mg/day can reduce the incidence, duration, and severity of neratinib-associated diarrhea in patients with early-stage breast cancer. Dose escalation has been included in the FDA-approved label for both early-stage and metastatic HER2+ breast cancer since June 2021. CASE SERIES: This series of five cases details real-world clinical implementation of strategies for management of neratinib-induced diarrhea in patients with early-stage and metastatic HER2+ breast cancer, including a patient with a pre-existing gastrointestinal disorder. MANAGEMENT AND OUTCOME: In four of five cases, diarrhea was managed with neratinib dose escalation, and antidiarrheal prophylaxis with loperamide plus colestipol was used in the remaining case. Management of diarrhea allowed all patients to remain on therapy. DISCUSSION: This case series shows that neratinib-associated diarrhea can be managed effectively with neratinib dose escalation from a lower initial starting dose and/or prophylactic antidiarrheal medications in a real-world clinical setting. The findings highlight the importance of patient-provider communication in proactive management of adverse events. Widespread implementation of the strategies described here may improve adherence and thereby clinical outcomes for patients with HER2+ breast cancer treated with neratinib

Spherical Collapse in Modified Newtonian Dynamics (MOND)

Modeling the structure formation in the universe, we extend the spherical collapse model in the context of MOND starting with the linear Newtonian structure formation followed by the MONDian evolution. In MOND the formation of structures speed up without a need for dark matter. Starting with the top-hat over-dense distribution of the matter, the structures virialize with a power--law profile of the distribution of matter. We show that the virialization process takes place gradually from the center of the structure to the outer layers. In this scenario the smaller structures enter to the MONDian regime earlier and evolve faster, hence they are older than larger structures. We also show that the virialization of the structures occur in the MONDian regime, in which the smaller structures have stronger gravitational acceleration than the larger ones. This feature of the dynamical behavior of the structures is in agreement with this fact that the smaller structures as the globular clusters or galactic bulges have been formed earlier and need less dark matter in CDM scenario.Comment: 23 pages, 7 figures, ApJ accepte

Integrated and Open Interpreter Education: The Open Educational Resource Reader and Workbook for Interpreters

https://digitalcommons.wou.edu/facbooks/1001/thumbnail.jp

Long-Term Follow-Up of a Phase I/II Trial of Dose Escalating Three-Dimensional Conformal Thoracic Radiation Therapy with Induction and Concurrent Carboplatin and Paclitaxel in Unresectable Stage IIIA/B Non-small Cell Lung Cancer

BACKGROUND: We conducted a modified phase I/II trial investigating the incorporation of three-dimensional conformal thoracic radiation therapy (TCRT) into the treatment paradigm of induction and concurrent carboplatin and paclitaxel in patients with unresectable stage IIIA/B non-small cell lung cancer. METHODS: Patients received 2 cycles of induction carboplatin (area under the curve of 6) and paclitaxel (225 mg/m) on days 1, and 22. On day 43 concurrent TCRT and weekly x6 of carboplatin (area under the curve = 2) and paclitaxel (45 mg/m) was initiated. The TCRT dose was escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy), and the 74 Gy cohort was expanded into a phase II trial. RESULTS: Sixty-two patients were enrolled; the median age 57 years (range, 36-82), 39 were male (63%), 61 (98%) had a performance status of 0 or 1, 28 (45%) had stage IIIA disease, 21 (34%) had >5% weight loss, and the median forced expiratory volume 1 = 2.10 liters (range, 1.02-3.75). With a median follow-up for survivors of approximately 9 years (range, 7-11 years) the median progression-free survival, time to tumor progression, and overall survival (OS) (with 95% confidence intervals) were 10 (8.5-17), 15 (9-50), and 25 months (18-37), respectively. The 5-year progression-free survival and OS rates were 21% (12-32%) and 27% (17-39%), respectively. The 10-year OS rate was 14% (7-25%). CONCLUSION: The long term survival rate compares favorably to other treatment approaches for stage III non-small cell lung cancer

Reconciling MOND and dark matter?

Observations of galaxies suggest a one-to-one analytic relation between the inferred gravity of dark matter at any radius and the enclosed baryonic mass, a relation summarized by Milgrom's law of modified Newtonian dynamics (MOND). However, present-day covariant versions of MOND usually require some additional fields contributing to the geometry, as well as an additional hot dark matter component to explain cluster dynamics and cosmology. Here, we envisage a slightly more mundane explanation, suggesting that dark matter does exist but is the source of MOND-like phenomenology in galaxies. We assume a canonical action for dark matter, but also add an interaction term between baryonic matter, gravity, and dark matter, such that standard matter effectively obeys the MOND field equation in galaxies. We show that even the simplest realization of the framework leads to a model which reproduces some phenomenological predictions of cold dark matter (CDM) and MOND at those scales where these are most successful. We also devise a more general form of the interaction term, introducing the medium density as a new order parameter. This allows for new physical effects which should be amenable to observational tests in the near future. Hence, this very general framework, which can be furthermore related to a generalized scalar-tensor theory, opens the way to a possible unification of the successes of CDM and MOND at different scales.Comment: 9 page

Induction Chemotherapy with Carboplatin, Irinotecan, and Paclitaxel Followed by High Dose Three-Dimension Conformal Thoracic Radiotherapy (74 Gy) with Concurrent Carboplatin, Paclitaxel, and Gefitinib in Unresectable Stage IIIA and Stage IIIB Non-small Cell Lung Cancer

Combined modality therapy is a standard therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in advanced NSCLC, and in preclinical models, it potentiates the activity of radiation therapy. We investigate the tolerability of gefitinib in combined modality therapy in combination with three-dimensional thoracic conformal radiation therapy (3-dimensional TCRT).Stage III patients with a good performance status were treated with induction chemotherapy (carboplatin area under the curve [AUC] of 5, irinotecan 100 mg/m2, and paclitaxel 175 mg/m2 days 1 and 22) with pegfilgrastim support followed by concurrent chemotherapy (carboplatin AUC 2, and paclitaxel 45 mg/m2 weekly) and gefitinib 250 mg daily beginning on day 43 with 3-dimensional TCRT to 74 Gy.Between March 2004 and January 2006, 23 patients received treatment on the trial: median age 62 years (range 44–82), 52% female, 61% stage IIIA, 61% performance status 0, 17% ≥5% weight loss, and 91% underwent positron emission tomography staging. Induction chemotherapy with pegfilgrastim support was well tolerated and active (partial response rate, 24%; stable disease, 76%; and early progression, 0%). Twenty-one patients initiated the concurrent chemoradiation, and 20 patients completed therapy to 74 Gy. The primary toxicities of concurrent chemoradiation were grade 3 esophagitis (19.5%) and cardiac arrhythmia (atrial fibrillation) (9.5%). The median progression-free survival and overall survival were 9 months (95% confidence intervals [CI]: 7–13 months) and 16 months (95% CI: 10–20 months), respectively.Treatment with induction chemotherapy and gefitinib concurrent with 3-dimensional TCRT has an acceptable toxicity and tolerability, but the survival results were disappointing

Adrenal-permissive HSD3B1 genetic inheritance and risk of estrogen-driven postmenopausal breast cancer.

BACKGROUNDGenetics of estrogen synthesis and breast cancer risk has been elusive. The 1245A→C missense-encoding polymorphism in HSD3B1, which is common in White populations, is functionally adrenal permissive and increases synthesis of the aromatase substrate androstenedione. We hypothesized that homozygous inheritance of the adrenal-permissive HSD3B1(1245C) is associated with postmenopausal estrogen receptor-positive (ER-positive) breast cancer.METHODSA prospective study of postmenopausal ER-driven breast cancer was done for determination of HSD3B1 and circulating steroids. Validation was performed in 2 other cohorts. Adrenal-permissive genotype frequency was compared between postmenopausal ER-positive breast cancer, the general population, and postmenopausal ER-negative breast cancer.RESULTSProspective and validation studies had 157 and 538 patients, respectively, for the primary analysis of genotype frequency by ER status in White female breast cancer patients who were postmenopausal at diagnosis. The adrenal-permissive genotype frequency in postmenopausal White women with estrogen-driven breast cancer in the prospective cohort was 17.5% (21/120) compared with 5.4% (2/37) for ER-negative breast cancer (P = 0.108) and 9.6% (429/4451) in the general population (P = 0.0077). Adrenal-permissive genotype frequency for estrogen-driven postmenopausal breast cancer was validated using Cambridge and The Cancer Genome Atlas data sets: 14.4% (56/389) compared with 6.0% (9/149) for ER-negative breast cancer (P = 0.007) and the general population (P = 0.005). Circulating androstenedione concentration was higher with the adrenal-permissive genotype (P = 0.03).CONCLUSIONAdrenal-permissive genotype is associated with estrogen-driven postmenopausal breast cancer. These findings link genetic inheritance of endogenous estrogen exposure to estrogen-driven breast cancer.FUNDINGNational Cancer Institute, NIH (R01CA236780, R01CA172382, and P30-CA008748); and Prostate Cancer Foundation Challenge Award