A Survey of Local Group Galaxies Currently Forming Stars: III. A Search for Luminous Blue Variables and Other H-alpha Emission-Lined Stars

We describe a search for H-alpha emission-lined stars in M31, M33, and seven dwarfs in or near the Local Group (IC 10, NGC 6822, WLM, Sextans B, Sextans A, Pegasus and the Phoenix dwarf) using interference filter imaging with the KPNO and CTIO 4-m telescope and Mosaic cameras. The survey is aimed primarily at identifying new Luminous Blue Variables (LBVs) from their spectroscopic similarity to known LBVs, avoiding the bias towards photometric variability, which may require centuries to manifest itself if LBVs go through long quiescent periods. Followup spectroscopy with WIYN confirms that our survey detected a wealth of stars whose spectra are similar to the known LBVs. We "classify" the spectra of known LBVs, and compare these to the spectra of the new LBV candidates. We demonstrate spectacular spectral variability for several of the new LBV candidates, such as AM2, previously classified as a Wolf-Rayet star, which now shows FeI, FeII and Balmer emission lines but neither the NIII 4634,42 nor HeII 4686 emission that it did in 1982. Profound spectral changes are also noted for other suspected and known LBVs. Several of the LBV candidates also show >0.5 mag changes in V over the past 10-20 years. The number of known or suspected LBVs is now 24 in M31, 37 in M33, 1 in NGC 6822, and 3 in IC 10. We estimate that the total number of LBVs in M31 and M33 may be several hundred, in contrast to the 8 known historically through large-scale photometric variability. This has significant implications for the time scale of the LBV phase. We also identify a few new WRs and peculiar emission-lined objects.Comment: Accepted by the Astronomical Journal. Version with higher quality figures may be downloaded from http://www.lowell.edu/users/massey/has.pdf.g

Change in Composition of the Anopheles Gambiae Complex and its Possible Implications for the Transmission of Malaria and Lymphatic Filariasis in North-Eastern Tanzania.

A dramatic decline in the incidence of malaria due to Plasmodium falciparum infection in coastal East Africa has recently been reported to be paralleled (or even preceded) by an equally dramatic decline in malaria vector density, despite absence of organized vector control. As part of investigations into possible causes for the change in vector population density, the present study analysed the Anopheles gambiae s.l. sibling species composition in north-eastern Tanzania. The study was in two parts. The first compared current species complex composition in freshly caught An. gambiae s.l. complex from three villages to the composition reported from previous studies carried out 2-4 decades ago in the same villages. The second took advantage of a sample of archived dried An. gambiae s.l. complex specimens collected regularly from a fourth study village since 2005. Both fresh and archived dried specimens were identified to sibling species of the An. gambiae s.l. complex by PCR. The same specimens were moreover examined for Plasmodium falciparum and Wuchereria bancrofti infection by PCR. As in earlier studies, An. gambiae s.s., Anopheles merus and Anopheles arabiensis were identified as sibling species found in the area. However, both study parts indicated a marked change in sibling species composition over time. From being by far the most abundant in the past An. gambiae s.s. was now the most rare, whereas An. arabiensis had changed from being the most rare to the most common. P. falciparum infection was rarely detected in the examined specimens (and only in An. arabiensis) whereas W. bancrofti infection was prevalent and detected in all three sibling species. The study indicates that a major shift in An. gambiae s.l. sibling species composition has taken place in the study area in recent years. Combined with the earlier reported decline in overall malaria vector density, the study suggests that this decline has been most marked for An. gambiae s.s., and least for An. arabiensis, leading to current predominance of the latter. Due to differences in biology and vectorial capacity of the An. gambiae s.l. complex the change in sibling species composition will have important implications for the epidemiology and control of malaria and lymphatic filariasis in the study area

Computer Simulations of Supercooled Liquids and Glasses

After a brief introduction to the dynamics of supercooled liquids, we discuss some of the advantages and drawbacks of computer simulations of such systems. Subsequently we present the results of computer simulations in which the dynamics of a fragile glass former, a binary Lennard-Jones system, is compared to the one of a strong glass former, SiO_2. This comparison gives evidence that the reason for the different temperature dependence of these two types of glass formers lies in the transport mechanism for the particles in the vicinity of T_c, the critical temperature of mode-coupling theory. Whereas the one of the fragile glass former is described very well by the ideal version of mode-coupling theory, the one for the strong glass former is dominated by activated processes. In the last part of the article we review some simulations of glass formers in which the dynamics below the glass transition temperature was investigated. We show that such simulations might help to establish a connection between systems with self generated disorder (e.g. structural glasses) and quenched disorder (e.g. spin glasses).Comment: 37 pages of Latex, 11 figures, to appear as a Topical Review article in J. Phys.: Condens. Matte

Evaluation of antibody response to Plasmodium falciparum in children according to exposure of Anopheles gambiae s.l or Anopheles funestus vectors

<p>Abstract</p> <p>Background</p> <p>In sub-Saharan areas, malaria transmission was mainly ensured by <it>Anopheles. gambiae </it>s.l. and <it>Anopheles. funestus </it>vectors. The immune response status to <it>Plasmodium falciparum </it>was evaluated in children living in two villages where malaria transmission was ensured by dissimilar species of <it>Anopheles </it>vectors (<it>An. funestus vs An. gambiae </it>s.l.).</p> <p>Methods</p> <p>A multi-disciplinary study was performed in villages located in Northern Senegal. Two villages were selected: Mboula village where transmission is strictly ensured by <it>An. gambiae </it>s.l. and Gankette Balla village which is exposed to several <it>Anopheles </it>species but where <it>An. funestus </it>is the only infected vector found. In each village, a cohort of 150 children aged from one to nine years was followed during one year and IgG response directed to schizont extract was determined by ELISA.</p> <p>Results</p> <p>Similar results of specific IgG responses according to age and <it>P. falciparum </it>infection were observed in both villages. Specific IgG response increased progressively from one-year to 5-year old children and then stayed high in children from five to nine years old. The children with <it>P. falciparum </it>infection had higher specific antibody responses compared to negative infection children, suggesting a strong relationship between production of specific antibodies and malaria transmission, rather than protective immunity. In contrast, higher variation of antibody levels according to malaria transmission periods were found in Mboula compared to Gankette Balla. In Mboula, the peak of malaria transmission was followed by a considerable increase in antibody levels, whereas low and constant anti-malaria IgG response was observed throughout the year in Gankette Balla.</p> <p>Conclusion</p> <p>This study shows that the development of anti-malaria antibody response was profoundly different according to areas where malaria exposure is dependent with different <it>Anopheles </it>species. These results are discussed according to i) the use of immunological tool for the evaluation of malaria transmission and ii) the influence of <it>Anopheles </it>vectors species on the regulation of antibody responses to <it>P. falciparum</it>.</p

The Influence of Brain Metastases on the Central Nervous System Effects of Methylnaltrexone: a Post Hoc Analysis of 3 Randomized, Double-Blind Studies

PURPOSE: Peripherally acting μ-opioid receptor antagonists such as methylnaltrexone (MNTX, Relistor METHODS: This post hoc analysis of pooled data from 3 randomized, placebo-controlled trials included cancer patients with OIC who received MNTX or placebo. Endpoints included changes from baseline in pain scores, rescue-free laxation (RFL) within 4 or 24 h of the first dose, and treatment-emergent adverse events (TEAEs), including those potentially related to opioid withdrawal symptoms. RESULTS: Among 356 cancer patients in the pooled population, 47 (MNTX n = 27; placebo n = 20) had brain metastases and 309 (MNTX n = 172; placebo n = 137) did not have brain metastases. No significant differences in current pain, worst pain, or change in pain scores from baseline were observed between patients treated with MNTX or placebo. Among patients with brain metastases, a significantly greater proportion of patients who received MNTX versus placebo achieved an RFL within 4 h after the first dose (70.4% vs 15.0%, respectively, p = 0.0002). TEAEs were similar between treatment groups and were generally gastrointestinal in nature and not related to opioid withdrawal. CONCLUSION: Focal disruptions of the BBB caused by brain metastases did not appear to alter central nervous system penetrance of MNTX

Phase II randomized trial of a non-steroidal mouth wash for prevention and treatment of stomatitis in women with hormone receptor positive breast cancer treated with everolimus.

BackgroundStomatitis is a frequent dose limiting toxicity of everolimus, an approved therapy for patients with metastatic breast cancer. No randomized trials of a prophylactic measure to prevent mucositis have been reported.MethodsWe conducted a phase II, open-label trial in which patients with metastatic breast cancer starting everolimus were randomized to best supportive care (BSC) versus prophylactic use of an oral mucoadhesive, non-steroid containing mouth wash. The primary endpoint was rate of any grade stomatitis as reported by the treating physicians. Secondary endpoints were severity of stomatitis according to the Oral Mucositis Assessment Scale (OMAS) and rates of everolimus dose reduction or discontinuation due to mucositis.ResultsOf 61 evaluable patients, 32 were randomized to and treated with oral mucoadhesive and 29 with BSC. Any grade stomatitis developed in 46.9% (15/32) of study arm and 65.5% (19/29) of BSC arm patients (p = 0.14). The difference between the two arms was significantly in favor of the mucoadhesive arm when mucositis was scored according to the OMAS with average score of 0.3 in study arm versus 0.5 in the control arm (p = 0.03). There were fewer dose adjustments or therapy discontinuations in the study arm compared with BSC (16% versus 31%, respectively) but the difference did not reach statistical significance.ConclusionHere we provide early evidence from the first randomized trial supporting the use of oral prophylactic mucoadhesive for everolimus-associated stomatitis. A trial comparing prophylactic oral mucoadhesive to steroid mouth wash may be warranted

Electroacupuncture for the management of symptom clusters in cancer patients and survivors (EAST)

BackgroundNeuropsychiatric symptoms, comprising cognitive impairment, fatigue, insomnia, depression, and anxiety, are prevalent and may co-occur during and after chemotherapy treatment for cancer. Electroacupuncture (EA), which involves mild electrical stimulation with acupuncture, holds great potential in addressing the management of individual symptoms. However, there is a lack of studies evaluating if EA can manage concurrent neuropsychiatric symptoms in cancer (i.e., symptom cluster). Hence, we designed a trial to evaluate the efficacy, safety, and feasibility of administering EA as an intervention to mitigate neuropsychiatric symptom clusters amongst cancer patients and survivors.MethodsThe EAST study is a randomized, sham-controlled, patient- and assessor-blinded clinical trial. Sixty-four cancer patients and survivors with complaints of one or more neuropsychiatric symptom(s) in the seven days prior to enrollment are recruited from the University of California Irvine (UCI) and Children's Hospital of Orange County (CHOC). Individuals with needle phobia, metastases, bleeding disorders, electronic implants, epilepsy, exposure to acupuncture in the three months prior to enrollment, and who are breastfeeding, pregnant, or planning to get pregnant during the duration of the study will be excluded. Screening for metal fragments and claustrophobia are performed prior to the optional neuroimaging procedures. Recruited patients will be randomized (1:1) in random blocks of four or six to receive either ten weekly verum EA (treatment arm, vEA) or weekly sham EA (control arm, sEA) treatment visits with a follow-up appointment four to twelve weeks after their last treatment visit. The treatment arm will receive EA at 13 acupuncture points (acupoints) chosen for their therapeutic effects, while the control arm receives minimal EA at 7 non-disease-related acupoints. Questionnaires and cognitive assessments are administered, and blood drawn to assess changes in symptom clusters and biomarkers, respectively.ConclusionThe EAST study can provide insight into the efficacy of EA, an integrative medicine modality, in the management of cancer symptom clusters in routine clinical practice.Trial registrationThis trial is registered with clinicaltrials.gov NCT05283577

High-dose infusional doxorubicin and cyclophosphamide: A feasibility study of tandem high-dose chemotherapy cycles without stem cell support

The purpose of this study was to determine the maximally tolerated dose of doxorubicin administered during two cycles of intensive chemotherapy with cyclophosphamide and doxorubicin without stem cell support in patients with advanced cancer and to assess the cumulative cardiac toxicity of the regimen by noninvasive radionuclide imaging and by pre- and postchemotherapy endomyocardial biopsies. Thirty-eight patients (thirty-six with high risk or metastatic breast cancer) were treated in a dose-escalation trial using a fixed dose of i.v. cyclophosphamide (4.2 g/m2) administered over 2 h on day 5 and escalating doses of doxorubicin (50-175 mg/m2) given as a 96-h continuous i.v. infusion on days 1-4, using Filgrastim (granulocyte colony- stimulating factor) for hematological support beginning on day 6. All patients underwent pretreatment, and 28 patients underwent postchemotherapy endomyocardial biopsies. Twenty-nine of 38 patients received two cycles of treatment (median number of days between cycles, 44; range, 34-62). Twenty- one patients had received doxorubicin previously at cumulative dose levels ≤150 mg/m2; all patients had pretreatment endomyocardial biopsy scores less than 1. One patient treated at the highest dose level of doxorubicin (175 mg/m2) developed symptoms of mild congestive heart failure following two cycles of chemotherapy. Pre- and posttreatment radionuclide ejection fractions were 65 and 45%, respectively; this patient had a posttreatment endomyocardial biopsy score of 1 (damage to \u3c5% of myocytes). One additional patient at this dose level had an asymptomatic biopsy score of 1, with a decrease in ejection fraction from 62 to 43%; this recovered to 58% 5 months after completion of chemotherapy. Six additional patients treated at lower dose levels had abnormal posttreatment endomyocardial biopsies without abnormal posttreatment ejection fractions. Nine patients received only one cycle of chemotherapy: five patients due to decreased cardiac ejection fraction following cycle 1 (two of these patients had normal endomyocardial biopsies, and two patients had biopsy scores of 1); one patient secondary to tumor progression following cycle one; one patient due to persistently detectable Clostridium difficile toxin in the stool; one patient refused cycle two; and one patient died following cycle one of complications related to sepsis. A single patient experienced a grand mal seizure associated with orthostatic hypotension, which was considered the dose-limiting toxicity. The median duration (over two cycles) of granulocytopenia (absolute granulocyte count \u3c500/μl) at the maximally tolerated dose level of 150 mg/m2 was 8.5 days (range, 5-13 days), and the median duration of thrombocytopenia (platelets \u3c20,000/μl) was 2.5 days (range, 0-9 days). The median duration of hospitalization including chemotherapy administration was 23 days (range, 19-36 days). Other toxicities included stomatitis, fever, diarrhea, and emesis. One patient developed acute leukemia 54 months posttreatment. We conclude that two courses of high-dose cyclophosphamide and doxorubicin using granulocyte colony-stimulating factor are feasible and safe with tolerable myocardial toxicity as evidenced by serial endomyocardial biopsies. The dose- limiting toxicity encountered was a grand mal seizure. The recommended Phase II dose is doxorubicin 150 mg/m2 administered as a 96-h infusion on days 1- 4, with cyclophosphamide 4.2 g/m2 on day 5 and G-CSF 5 μg/kg/day started on day 6 and administered until the total WBC is above 10,000/μl for three consecutive days