A fourteen-year review of breast pathology at a rural referral center in western Kenya

Background: Breast cancer has a low incidence in Africa compared with other continents. Of breast cancer reported in Africa, middle and eastern Africa is reported with the lowest incidence. In general, there is a paucity of information about breast cancer in Africa. Breast cancer evaluation and treatment is plagued with inadequate resource and screening facility throughout sub-Saharan Africa. Therefore, it is difficult to adequately assess incidence or prevalence without appropriate cancer or death registries. To our knowledge, no data exists for breast cancer treated in rural Kenya.Methods: Review of all surgical pathology reports was performed from January 31, 1993 to August 31, 2007 at Tenwek Hospital, a 300 bed referral center located in Bomet, Kenya. Records were searched for any breast specimen or specimen related to breast disease such as metastatic breast disease.Results: For the studied period, a total of 118 breast cancers were identified from pathology report records. Men accounted for 13 (11.02%) of all breast cancers. The average age for men was 69 years (std 10.6). The average age of women (n=105) was 51.2 years (std 15.6). The difference between the mean ages among men and women was statistically significant (p=0.000195). Grades were listed for only 55 of 118 specimens. Grade 3 was recorded in 61.8% (34/55). Women, aged 50 years or less, comprised 59.3% of all women recorded ages. In females, Grade 1 occurred in 7.1%, Grade 2 in 39.3%, and Grade 3 in 53.6%. Average age for Grade 1 histology is 37.5 years (std 2.1), Grade 2 average was 38.3 years (std 5.9) and Grade 3 average age was 40.8 years (std 5.7). The majority of males had IDC (12/13) with one case of NHL and melanoma of the breast

Isotopic analysis of faunal material from South Uist, Western Isles, Scotland

This paper reports on the results from stable isotope analysis of faunal bone collagen from a number of Iron Age and later sites on the island of South Uist, in the Western Isles, Scotland. This preliminary investigation into the isotopic signatures of the fauna is part of a larger project to model the interaction between humans, animals, and the broader environment in the Western Isles. The results demonstrate that the island fauna data fall within the range of expected results for the UK, with the terrestrial herbivorous diets of cattle and sheep confi rmed. The isotopic composition for pigs suggests that some of these animals had an omnivorous diet, whilst a single red deer value might be suggestive of the consumption of marine foods, such as by grazing on seaweed. However, further analysis is needed in order to verify this anomalous isotopic ratio

Chemotherapy following radium-223 dichloride treatment in ALSYMPCA

BACKGROUND Radium-223 prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases, regardless of prior docetaxel. Whether or not chemotherapy can be safely administered following radium-223 treatment is of clinical importance. An exploratory analysis of prospectively collected data, from the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) patient subgroup who received chemotherapy after radium-223 or placebo treatment, was conducted to evaluate the safety and efficacy of chemotherapy following radium-223. METHODS In ALSYMPCA, CRPC patients with symptomatic bone metastases and no visceral metastases were randomized 2:1 to receive six injections of radium-223 (50 kBq/kg IV) or placebo plus best standard of care, stratified by prior docetaxel, baseline alkaline phosphatase, and current bisphosphonate use. In this exploratory analysis, chemotherapy agents administered following study treatment were identified; timing and duration were calculated. Hematologic safety was reviewed, and overall survival analyzed. RESULTS Overall, 142 radium-223 and 64 placebo patients received subsequent chemotherapy; most common were docetaxel (70% radium-223, 72% placebo) and mitoxantrone (16% radium-223, 20% placebo). The majority of patients (61% radium-223, 58% placebo) had received prior docetaxel. Radium-223 patients started subsequent chemotherapy later than placebo patients; chemotherapy duration was similar between groups. In radium-223 and placebo patients receiving subsequent chemotherapy, median hematologic values (hemoglobin, neutrophils, and platelets) remained nearly constant up to 18 months following start of chemotherapy, regardless of prior docetaxel treatment. A low percentage of patients in both groups had grades 3–4 hematologic values (<10%). Platelet count decline, from last measurement before chemotherapy, was numerically greater in radium-223 versus placebo patients. Median overall survivals from start of chemotherapy were 16.0 and 15.8 months following radium-223 and placebo, respectively. CONCLUSIONS Chemotherapy following radium-223, regardless of prior docetaxel, is feasible and appears to be well tolerated in patients with CRPC and symptomatic bone metastases

Efficacy and Safety of Radium-223 Dichloride in Symptomatic Castration-resistant Prostate Cancer Patients With or Without Baseline Opioid Use From the Phase 3 ALSYMPCA Trial

Background: The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use. Objective: To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use. Design, setting, and participants: Nine hundred and twenty one patients enrolled at 136 centers globally. Intervention: Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care. Outcome measurements and statistical analysis: Primary endpoint (overall survival [OS]), main secondary efficacy endpoints, and safety were evaluated by baseline opioid use. Additional analyses included time to first opioid use, time to first external beam radiation therapy for bone pain, and safety of concomitant external beam radiation therapy. Results and limitations: At baseline, 408 (44%) patients had no pain and no analgesic use or mild pain with nonopioid therapy (World Health Organization ladder pain score 0–1 [nonopioid subgroup]), and 513 (56%) had moderate pain with occasional opioids or severe pain with regular daily opioids (World Health Organization ladder pain score 2–3 [opioid subgroup]). Radium-223 significantly prolonged OS versus placebo in nonopioid (hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.52–0.93; p = 0.013) and opioid (HR = 0.68; 95% CI: 0.54–0.86; p = 0.001) subgroups, and significantly reduced risk of symptomatic skeletal events versus placebo, regardless of baseline opioid use (nonopioid subgroup: HR = 0.56, 95% CI: 0.39– 0.82, p = 0.002; opioid subgroup: HR = 0.72, 95% CI: 0.53–0.98, p = 0.038). Time to first opioid use for bone pain was significantly delayed with radium-223 versus placebo (HR = 0.62, 95% CI: 0.46–0.85, p = 0.002). Adverse event incidences were similar between opioid subgroups. Conclusions: Radium-223 versus placebo significantly prolonged OS and reduced symptomatic skeletal event risk with a favorable safety profile in castration-resistant prostate cancer patients with symptomatic bone metastases, regardless of baseline opioid use. Patient summary: In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safet

Four-point Green functions in the Schwinger Model

The evaluation of the 4-point Green functions in the 1+1 Schwinger model is presented both in momentum and coordinate space representations. The crucial role in our calculations play two Ward identities: i) the standard one, and ii) the chiral one. We demonstrate how the infinite set of Dyson-Schwinger equations is simplified, and is so reduced, that a given n-point Green function is expressed only through itself and lower ones. For the 4-point Green function, with two bosonic and two fermionic external `legs', a compact solution is given both in momentum and coordinate space representations. For the 4-fermion Green function a selfconsistent equation is written down in the momentum representation and a concrete solution is given in the coordinate space. This exact solution is further analyzed and we show that it contains a pole corresponding to the Schwinger boson. All detailed considerations given for various 4-point Green functions are easily generizable to higher functions.Comment: In Revtex, 12 pages + 2 PostScript figure

Combined kinase inhibitors of MEK1/2 and either PI3K or PDGFR are efficacious in intracranial triple-negative breast cancer

Background: Triple-negative breast cancer (TNBC), lacking expression of hormone and human epidermal growth factor receptor 2 receptors, is an aggressive subtype that frequently metastasizes to the brain and has no FDA-approved systemic therapies. Previous literature demonstrates mitogen-Activated protein kinase kinase (MEK) pathway activation in TNBC brain metastases. Thus, we aimed to discover rational combinatorial therapies with MEK inhibition, hypothesizing that co-inhibition using clinically available brain-penetrant inhibitors would improve survival in preclinical models of TNBC brain metastases. Methods: Using human-derived TNBC cell lines, synthetic lethal small interfering RNA kinase screens were evaluated with brain-penetrant inhibitors against MEK1/2 (selumetinib, AZD6244) or phosphatidylinositol-3 kinase (PI3K; buparlisib, BKM120). Mice bearing intracranial TNBC tumors (SUM149, MDA-MB-231Br, MDA-MB-468, or MDA-MB-436) were treated with MEK, PI3K, or platelet derived growth factor receptor (PDGFR; pazopanib) inhibitors alone or in combination. Tumors were analyzed by western blot and multiplexed kinase inhibitor beads/mass spectrometry to assess treatment effects. Results: Screens identified MEK+PI3K and MEK+PDGFR inhibitors as tractable, rational combinations. Dual treatment of selumetinib with buparlisib or pazopanib was synergistic in TNBC cells in vitro. Both combinations improved survival in intracranial SUM149 and MDA-MB-231Br, but not MDA-MB-468 or MDA-MB-436. Treatments decreased mitogen-Activated protein kinase (MAPK) and PI3K (Akt) signaling in sensitive (SUM149 and 231Br) but not resistant models (MDA-MB-468). Exploratory analysis of kinome reprogramming in SUM149 intracranial tumors after MEK PI3K inhibition demonstrates extensive kinome changes with treatment, especially in MAPK pathway members. Conclusions: Results demonstrate that rational combinations of the clinically available inhibitors selumetinib with buparlisib or pazopanib may prove to be promising therapeutic strategies for the treatment of some TNBC brain metastases. Additionally, effective combination treatments cause widespread alterations in kinase pathways, including targetable potential resistance drivers

Long-term stability of planets in and around binary stars

Planets are observed to orbit the component star(s) of stellar binary systems on so-called circumprimary or circumsecondary orbits, as well as around the entire binary system on so-called circumbinary orbits. Depending on the orbital parameters of the binary system a planet will be dynamically stable if it orbits within some critical separation of the semimajor axis in the circumprimary case, or beyond some critical separation for the circumbinary case. We present N-body simulations of star-forming regions that contain populations of primordial binaries to determine the fraction of binary systems that can host stable planets at various semimajor axes, and how this fraction of stable systems evolves over time. Dynamical encounters in star-forming regions can alter the orbits of some binary systems, which can induce long-term dynamical instabilities in the planetary system and can even change the size of the habitable zone(s) of the component stars. However, the overall fraction of binaries that can host stable planetary systems is not greatly affected by either the assumed binary population, or the density of the star-forming region. Instead, the critical factor in determining how many stable planetary systems exist in the Galaxy is the stellar binary fraction – the more stars that are born as singles in stellar nurseries, the higher the fraction of stable planetary systems

Erratum to: Search for diboson resonances in hadronic final states in 139 fb−1 of pp collisions at s√ = 13 TeV with the ATLAS detector

A mistake was identified for the paper [1] in the treatment of the radion [2] cross-sections, which resulted in multiple changes.(undefined)info:eu-repo/semantics/publishedVersio

Online Interactive Teaching Modules Enhance Quantitative Proficiency of Introductory Biology Students

There is widespread agreement within the scientific and education communities that undergraduate biology curricula fall short in providing students with the quantitative and interdisciplinary problem-solving skills they need to obtain a deep understanding of biological phenomena and be prepared fully to contribute to future scientific inquiry. MathBench Biology Modules were designed to address these needs through a series of interactive, Web-based modules that can be used to supplement existing course content across the biological sciences curriculum. The effect of the modules was assessed in an introductory biology course at the University of Maryland. Over the course of the semester, students showed significant increases in quantitative skills that were independent of previous math course work. Students also showed increased comfort with solving quantitative problems, whether or not they ultimately arrived at the correct answer. A survey of spring 2009 graduates indicated that those who had experienced MathBench in their course work had a greater appreciation for the role of mathematics in modern biology than those who had not used MathBench. MathBench modules allow students from diverse educational backgrounds to hone their quantitative skills, preparing them for more complex mathematical approaches in upper-division courses