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ART NOTES | Alice Lynn Greenwood-Mathé for ArtCentralCarthage at Hyde House | on Facebook and in The Carthage Press and The Carthage Chronicle
Juror BETH SIMMONS
OUTSTANDING JURORS
artCentral's MEMBERSHIP EXHIBITION
Juror NANCY DUNAWAY
At last! After weeks of preparation artCentral's Annual Membership Exhibition (AME) opens at noon on Friday, June 4, 2021, and will continue through July 17. The Annual Picnic and Awards Presentation will be 6:00-8:00 p.m. on the lush Hyde House campus at 1110 East Thirteenth Street in Carthage. Weekend Gallery Hours during the Membership Exhibition are Saturdays and Sundays, 12:00-5:00 p.m. and other times by appointments made at (417) 358-4404.
The McCune-Brooks Healthcare Foundation is the gracious underwriter for artCentral's Annual Membership Exhibition. Believing art is an essential and vital dimension of any healthy and vital community, we are thankful that McCune-Brooks supports artCentral as one of the programs, organizations and initiatives that directly contributes to better health and healthy lifestyles for the citizens of Carthage.
Beth Simmons, Director of McCune-Brooks Healthcare Foundation, and Nancy Dunaway, art educator and practicing professional artist, two highly qualified women, have enthusiastically served as jurors for this outstanding collection of multi-media works by forty-two artCentral artists.
Recently Beth has very deservedly been named the Chamber of Commerce 2020 Carthage Citizen of the Year. Her years of experience, joie de vivre and dedicated leadership in our community set the bar high for all of us hoping to make a meaningful contribution to this hometown we love. Beth, an avid collector of art, is a longtime patron of artCentral and artCentral artists.
Artist Nancy Dunaway, of North Little Rock, Arkansas, has pulled off an amazing feat—many years working and mentoring young artists-in-the making while developing her own impressive body of work. We knew each other first as students in the art labs at Hendrix College in Conway, Arkansas, where we both majored in studio art. I love the Oliver Wendell Holmes quote and favorite duck adorned childhood photo Nancy offers as the introduction to her website: "A mind that is stretched by new experience can never go back to its old dimensions." This is certainly the creed that has guided Nancy's creative life. Following the trajectory of her artistic career, I am wowed by her accomplishments!
Be sure to check out Nancy's well-organized website representing the diversity of her portfolio at http://www.nancydunaway.org. There you will learn her art "is a reflection of her own life, very eclectic—a curious combination often inspired by a glimpse of something natural and taking a leap somewhere else. It tells stories of her journey, that, while specific to her in the making, hopefully connects somewhere with each viewer and touches their own story, too. She works in a variety of media including painting, mixed media, printmaking, assemblage and book art.
For fifteen years, Nancy served as Chair of the Art Department at Henderson State University in Arkadelphia, Arkansas, where she taught classes in Drawing, Illustration, Book Arts, Experimental and Contemporary Media and Art Education. She has exhibited her work regionally and nationally in many venues including the Delta Exhibition and Toys Designed by Artists, both at the Arkansas Arts Center, the American Drawing Biennial in Williamsburg, Virginia, the Peninsula Fine Arts Center in Newport News, Virginia, the Schneider Museum in Ashland, Oregon, St. John's College in Santa Fe, New Mexico, the Nabisco World Headquarters in East Hanover, New Jersey, and the Albuquerque Museum, to name a few. Her work, 'Drifting toward Dawn', was exhibited in the American Embassy in Brassaville, the Congo, as part of the US State Department's 'Art in Embassies Program'.
In 2001, Nancy received an Individual Artist Fellowship Award in Book Arts from the Arkansas Arts Council. She received her MFA, Summa Cum Laude, from Savannah College of Art & Design in Illustration, and has illustrated two children's books, 'The Old Lady Who Lived in a Vinegar Bottle', authored by Margery MacDonald, and 'I Scream, You Scream', authored by Lillian Morrison. Nancy's work is in many private and corporate collections. One of her artist's books, 'Hildegarde of Bingen', is a part of the permanent collection of the National Museum of Women in the Arts in Washington, D.C. Another of her artist's books, "Feathers & Findings", can be found in Lark's '500 Handmade Books'."
Beth Simmons and Nancy Dunaway, the outstanding jurors for artCentral's Annual Membership Exhibition have made fine choices of those artists and their works selected to receive 2021 awards. Do come see these award recipients and all the diverse talents that now fill the galleries of Hyde House!
Author
Executive Director-
Curator
for the love of Art &
for the love of Artists


Guild. The Guild were a group of volunteers who served as communal militia. Each head in the group was an individual portrait; each one a masterpiece.
His career peaked during the 1630's and 1640's as a portrait painter. In the 1630's he abandoned early bright colors for a monochrome effect and his portraits became more unified and simple, with poses more frontal. By the 1640's he painted portraits with a more aristocratic air but with less ostentatious poses. Most of his backgrounds were now dark and the clothing black. It is believed that he painted from the model, very quickly and with a limited palette. The immediacy and brilliance of his portraits brought sitters to life - they were said to "breathe". His innovative loose brushstrokes to depict light on form were seen by art critics of the 18th and early 19th centuries to be lazy and unfinished and his work was almost forgotten for two centuries. With the rise of "Realism" and "Impressionism" he has been hailed as a painter before his time.
His personal life was pretty much of a disaster. Nothing about him was attractive except that he was a great painter and a jolly soul. He was a drunkard and a wife beater. His first wife died in 1617 and he married again five months later to Lysbeth Reyniers who bore him ten (10) children - the first born five (5) days before their marriage. One son ended in the insane asylum and a daughter was sent to the workhouse. Hals himself was destitute by 1652 and died a pauper in 1666. His last great masterpiece was painted at this time (1664) entitled The Women Regents of the Old Men's Home in Haarlem.
While some in the past have decried his lack of range, ie. no religious pictures, landscapes or nudes, he is considered today as the most brilliant executant of portraits the world has seen.
Pieter Jacobz Olycan (1572-1658) was one of Haarlem's leading citizens. He was a wealthy brewer who also served the city as mayor and was a member of the States General, the governing body of Holland. Hals painted a number of portraits of the Olycan family including one of the sitter's wife Maritge Vooght Claesdr, which originally hung as a pendant of this portrait and which now hangs in the Rijksmuseum, Amsterdam. Olycan personifies and conveys the vitality of that era of Dutch history when Holland rose to become a mighty commercial and naval power.
This painting, a pendant of a portrait of the sitters wife, was cut down slightly at both the sides and at the top or bottom as proved by the measurements of the companion piece and the fact that the coat-of-arms in the upper right corner is only partially visible. In spite of this, the portrait is one of Hals' most imposing single portraits - it shows powerful characterization - and was counted by Valentiner as "among the most imposing and impressive of the master's works of the period around 1640". Olycan is placed in an aristocratic, frontal pose, typical of Hals' painting at this point in his career. He appears as a proud and successful statesman / businessman, who personifies the affluence and strength of Holland at this point in it's history.
While the portrait is painted with a limited number of colors, Hals produced an almost infinite number of nuances within the seemingly restricted range. It had been said that Hals' palette contained a hundred different blacks. The face has the broad, rapid brushwork which invests Olycan with a lifelike spontaneity, creating the illusion that the expression playing across his features has been captured in an instant. It seems that Olycan is speaking to us. The sense of exchange with the viewer, that lies at the heart of baroque portraiture, is certainly evident in this portrait.
The purchase of the portrait was a coup for Ringling in that Lord Duveen, the internationally known art dealer and collector, tried unsuccessfully to buy it from him for several times the amount he had paid for it.
The period in which Hals painted was the so called Golden Age of the Dutch Republic. It was a time of war with Spain during which the Dutch accomplished significant naval victories culminating in the Battle of the Downs when an entire Spanish fleet was sunk, disabled or captured. With each victory the Dutch merchants turned money into ships, for every victory on the sea expanded trade. In 1648 the Treaty of Westphalia ended the "Eighty Years War" in the Netherlands and freedom of trade (and wealth) was conceded to Dutch merchantmen in the East and West Indies.


Recombinant human endostatin (rh-endostatin) is a novel antiangiogenesis drug developed in China. Previous experiments have shown that rh-endostatin can inhibit the proliferation and migration of endothelial cells and some types of tumor cells. In this study, we evaluated the efficacy and safety profiles of combination therapy of rh-endostatin and neoadjuvant chemotherapy for breast cancer patients in a prospective, randomized, controlled, phase II trial.
Sixty-eight patients with core-biopsy confirmed breast cancer were allocated randomly to two groups to receive 3 cycles of intravenous administration of either neoadjuvant DE (docetaxel: 75 mg/m2, d1, epirubicin: 75 mg/m2, d1, every 3 weeks), or neoadjuvant DE combined with rh-endostatin (7.5 mg/m2, d1-d14, every 3 weeks). The primary end point was clinical response based upon Response Evaluation Criteria in Solid Tumors, and the secondary end point was safety and quality of life.
All patients were assessable for toxicity and 64 (94.2%) were assessable for efficacy evaluation. The objective response rate was 67.7% for chemotherapy (n = 31) and 90.9% for rh-endostatin plus chemotherapy (n = 33) (P = 0.021). A retrospective subset analysis revealed that rh-endostatin was more effective in premenopausal patients and patients with ECOG score of zero (P = 0.002 and P = 0.049, respectively). Five patients in the rh-endostatin plus chemotherapy arm achieved pathologic complete response compared with 2 in the chemotherapy arm (P = 0.428). No significant difference was identified in quality of life score and side effects (P > 0.05).
The combination of rh-endostatin with chemotherapy produced a higher tumor response rate without increasing toxicity in breast cancer patients.
Breast cancer is one of the most common malignancies in women and its incidence continues to increase . In the past 30 years, an improved understanding of the biological behavior of breast cancer has led to advancements in treatment.
Antiangiogenic therapy for cancer has attracted considerable attention. The rationale behind it is that tumor growth is dependent on angiogenesis , which was proposed by Dr. Folkman and has been confirmed by basic and clinical research. In 1997, O'Reilly et al. isolated a peptide with a molecular weight of about 20 kD from murine hemangioendothelioma. By amino acid sequencing, this peptide was identified as a fragment of C-terminal type XVIII collagen with anti-angiogenic effects and was named endostatin. Recent studies indicated that endostatin was one of the most effective angiogenesis inhibitors currently known. Endostatin can directly target capillary endothelial cells around the tumor without detectable toxicity in normal cells. It may also inhibit cell migration, induce cell apoptosis, and play a multitargeted antiangiogenic role by regulating expression of vascular endothelial growth factor (VEGF) and activity of proteolytic enzymes, indirectly leading to the quiescence or reduction of tumors .
Recombinant human endostatin (rh-endostatin) is a new protein modified by an additional nine-amino acid sequence to the N-terminal of endostatin. Preclinical study indicated that rh-endostatin could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. In 2001, rh-endostatin was approved by the State Food and Drug Administration of China (Approval No.: 2001SL029) for clinical research. From 2003 to 2004, Sun et al. conducted a randomized, double-blind, multicenter, phase III clinical trial comparing treatment of vinorelbine and cisplatin (NP) plus rh-endostatin and NP alone in non-small cell lung cancer (NSCLC) patients. The objective response rate (ORR) was 35.4% and 19.5% (P < 0.01), the median time to progression was 6.3 and 3.6 months (P < 0.001), the median survival time was 14.8 and 9.9 months (P < 0.001), and the 1-year survival rate was 62.7% and 31.5% (P < 0.001) in NP plus rh-endostatin group and NP alone group, respectively. These data indicated that rh-endostatin had synergistic effects with NP. Rh-endostatin not only increased tumor response rate, but also significantly improved the overall survival (OS) without increasing the adverse effects. In another multicenter, randomized, double-blind, placebo-controlled study published in 2011, treatment with paclitaxel and carboplatin (TC) plus rh-endostatin improved ORR in patients with advanced NSCLC and exhibited a good safety profile, although the differences in progression free survival (PFS) or OS were not statistically significant from TC alone .
All these findings suggest that rh-endostatin may be effective as well in the treatment of other solid tumors, including breast cancer. To test this hypothesis, we designed a prospective, randomized, controlled phase II clinical trial to determine the efficacy and safety of neoadjuvant docetaxel and epirubicin (DE) with or without rh-endostatin for breast cancer patients (ClinicalTrials.gov Identifier: NCT00604435). It is the first registered clinical trial gauging the impact of rh-endostatin on breast cancer therapy.
This study was a prospective, randomized, parallel controlled, phase II trial. The primary end point was clinical and pathological response, and the secondary end point was safety and quality of life (QOL). This study was approved by the Ethics Committee of Fourth Military Medical University to be in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants before enrollment.
The inclusion criteria were (1) female, aged 18–70 years, (2) histologically confirmed invasive breast cancer (core needle biopsy for breast cancer diagnosis and fine needle aspiration for lymph node metastasis diagnosis), stage IIA to IIIC, and to be treated with primary systemic therapy, (3) without previous treatment, (4) Eastern Cooperative Oncology Group (ECOG) performance status 0–2, (5) normal hematologic function, (6) left ventricular ejection fraction greater than 50%, and (7) adequate liver or kidney function tests. Exclusion criteria included (1) allergic constitution or possible allergic reaction to drugs to be used in this study, (2) any concurrent uncontrolled medical or psychiatric disorder, (3) history of severe heart diseases, including congestive heart failure, unstable angina, uncontrolled arrhythmia, myocardial infarction, uncontrolled high blood pressure, or heart valve disease, (4) history of bleeding diathesis, and (5) being pregnant or nursing.
All patients were prospectively registered in our central research database. Patients were randomly assigned to receive either 3 cycles of neoadjuvant DE (docetaxel: 75 mg/m2, d1, epirubicin: 75 mg/m2, d1, every 3 weeks), or 3 cycles of neoadjuvant DE and rh-endostatin (7.5 mg/m2, d1-d14, every 3 weeks) administered intravenously. Docetaxel was produced by Sanofi-Aventis Company, epirubicin by Pfizer Company, and rh-endostatin by Simcere-Medgenn Bio-Pharmaceuticals Company (National Medicine Permit No. S20050088).
At the time of diagnosis and after each cycle of therapy, the sizes of breast tumors and lymph nodes were measured, respectively, with physical examination and ultrasound . The clinical response was classified as follows, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 : complete response (CR), disappearance of all target lesions; partial response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of one or more new lesions; stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Tumor classified as CR or PR was defined as objective response (OR), and that classified as SD or PD was defined as no response (NR).
QOL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life of Questionnaire (EORTC QLQC30) questionnaire  at study entry, and prior to surgery. The adverse events during neoadjuvant therapy were graded based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 .
Following the completion of neoadjuvant therapy, all patients underwent Patey's radical mastectomy or lumpectomy plus axillary clearance and then received 3 to 6 cycles of adjuvant chemotherapy. The number of cycles was decided in terms of clinical staging, histological grade, clinical and pathological response, apoptosis index, and biological markers such as hormonal receptor status, Ki-67 index, and human epidermal growth factor receptor 2 (HER2) expression. Radiotherapy was given to most (87%) patients, including all breast conservative cases. Patients with positive estrogen receptor (ER) and/or progesterone receptor (PR) received 5 years of endocrine therapy. All participants were followed up at 6-month intervals in an outpatient clinic.
Tissue samples, collected from biopsy and surgery, were fixed in 4% neutral formalin for 24 h and then embedded in paraffin blocks. Sections were cut at 3 μm and mounted on glass slides overnight at room temperature. Histological classification and grading were made using light microscopy examination of tissue sections stained with H&E. Pathological response of breast tumor was defined as follows: (a) complete response (pCR), no residual viable invasive tumor, ie, only in situ disease or tumor stroma remained; and (b) nonresponse, any viable tumor . The status of hormone receptor and HER2 was examined by immunohistochemistry using a standard avidin-biotin complex technique [12, 13].
SPSS 11.0 for windows was used for statistical analysis. Normal distribution data were represented by mean ± standard deviation. Student's t test was used to compare the mean after checking the homogeneity of variance. Enumeration data was compared using x2 test, and Fisher's exact test was used for that with few cases. P < 0.05 was considered statistically significant.
From February 2008 to March 2010, 70 patients were enrolled in this study. Two of them failed to complete the first cycle of chemotherapy (one for economic reason and the other for uncontrollable hyperglycemia) and were excluded. Sixty-eight patients were assessable for toxicity and QOL evaluation and were randomly assigned to two groups. Two patients in each group failed to complete three cycles of primary systemic therapy (2 asked surgery ahead of schedule and 2 refused to continue chemotherapy), leaving 64 assessable for efficacy evaluation with 31 in DE group and 33 in DE plus rh-endostatin group.
The baseline characteristics of the study population including age, menopausal status, hormone receptor status, HER2 status, ECOG performance status, histology, axillary lymph node status, and clinical stage are given in Table 1. All these factors were well balanced between two groups (P > 0.05 for all comparison).
Abbreviations: DE, docetaxel and epirubicin; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; ECOG, Eastern Cooperative Oncology Group.
Of the 33 patients in DE plus rh-endostatin group, 4 (12.1%) achieved CR, 26 (78.8%) achieved PR, 1 (3.0%) exhibited SD, and 2 (6.1%) exhibited PD. Of the 31 patients in the chemotherapy alone group, 2 (6.5%) achieved CR, 19 (61.3%) PR, 9 (29.0%) SD, and 1 (3.2%) PD. The ORR in patients receiving chemotherapy with or without rh-endostatin were 90.9% (30/33) and 67.7% (21/31), respectively, with significant difference (x2 = 5.300, P = 0.021).
pCR was identified in 7 (10.9%) of all the 64 patients with 5 (15.2%) in the rh-endostatin plus chemotherapy arm and 2 (6.5%) in the chemotherapy alone arm. A higher pCR rate was achieved following the combination therapy, but without significant difference from chemotherapy alone (P = 0.428).
All the factors probably influencing the clinical response were stratified and analyzed. The factors included age, menopausal status, hormone receptor status, HER2 status, ECOG performance status, histology, axillary lymph node status, and clinical stage. No correlation was identified between ORR and age, hormone receptor status, HER2 status, histology, lymph node status or clinical stage (P > 0.05 for all). However, premenopausal women and those with ECOG score of zero demonstrated a significantly higher ORR (100% vs 46.3%, P = 0.002, and 94.4% vs 66.7%, P = 0.049, respectively). The details of stratification analysis are listed in Table 2.
Sixty-eight patients completed at least one cycle of treatment and received QOL assessment (Table 3). No significant difference was found between the two groups either before or after treatment (P > 0.05), indicating that rh-endostatin may exert little effect upon QOL of patients.
Abbreviations: QOL, quality of life; DE, docetaxel and epirubicin.
Sixty-eight patients were assessable for toxicity evaluation (Table 4). The total incidence of adverse events was 81.2% and 79.3%, respectively, in the rh-endostatin plus chemotherapy arm and chemotherapy alone arm. Most of the adverse events were of grade 1 and 2. Grade 3 and 4 adverse events included leucopenia, neutropenia, nausea, and vomiting. No significant difference was found between the two groups, either in the incidence of overall adverse events or in the incidence of grade 3/4 adverse events (P > 0.05 for all).
Abbreviation: DE, docetaxel and epirubicin.
Neoadjuvant chemotherapy, also known as preoperative or primary chemotherapy, is widely used in the management of breast cancer patients to treat occult systemic disease, reduce the tumor bulk, and increase the likelihood of breast conservation, while not affecting the local recurrence hazard [14, 15], or compromising survival . In the mean time, preoperative therapy provides an opportunity to gain more insight into the cellular and molecular changes involved in tumor response.
The current systemic treatment of breast cancer has been developed rapidly in the past 10 years. Compared with conventional cytotoxic chemotherapy, the systemic treatment is more sophisticated and specific, characterized by multiple cancer targets. One promising strategy is targeting the proangiogenic VEGF, either by ligand sequestration (preventing VEGF receptor binding) or inhibiting downstream receptor signaling . Thus far, more than 30 kinds of antiangiogenesis agents have been approved for clinical practice or ongoing preclinical and clinical trials.
Bevacizumab (Avastin), a recombinant humanized antibody against VEGF, is the first antiangiogenesis drug approved for clinical practice. A recent report of a pooled analyses of metastatic breast cancer (MBC) patients receiving bevacizumab-based therapy showed that the addition of bevacizumab significantly prolonged PFS time . Although the PFS interval might depend on the evaluation methods and schedules used, the PFS as a study endpoint currently represents the most sensitive parameter to assess the efficacy of an experimental drug in metastatic disease, especially when a longer PFS duration is associated with a higher ORR or a measurable improvement in QOL. The most common adverse effects of bevacizumab include headache, nausea, vomiting, anorexia, stomatitis, constipation, upper-respiratory-tract infection, epistaxis, dyspnea, and proteinuria. The most serious adverse effects include hypertensive crisis, nephritic syndrome, hemorrhage, gastrointestinal perforation, wound-healing complications, and congestive heart failure .
Rh-endostatin (Endostar) is a new recombinant humanized endostatin expressed and purified in E. coli. The additional nine-amino acid sequence to the N-terminal of endostatin may effectively simplify purification and improve the stability of the protein [19, 20], although the exact mechanism of rh-endostatin as antiangiogenesis drug remains unclear. Previous studies showed that endostatin may downregulates many signaling pathways in human microvascular endothelium associated with proangiogenic activity, and simultaneously upregulate many antiangiogenic genes [21, 22]. It was also found that endostatin could lower VEGF expression in colon and cervical cancer [23, 24]. Based on the positive data from a phase III trial , China State Food and Drug Administration approved rh-endostatin plus NP as a first line therapy for advanced NSCLC in 2005.
Angiogenesis is an important step in the proliferation of breast cancer cells and is thought to precede invasive disease . In situ hybridization revealed high levels of VEGF in ductal carcinoma in situ, infiltrating ductal carcinoma, and metastatic ductal carcinoma , further rationalizing the addition of rh-endostatin for breast cancer therapy. In this study, 68 patients with stage II or III primary breast cancer were allocated randomly to two groups to receive either 3 cycles of neoadjuvant DE, or 3 cycles of neoadjuvant DE plus rh-endostatin. The primary end point was to determine the impact of the addition of rh-endostatin on the clinical and pathologic response. Among the 64 patients assessable for efficacy evaluation, the ORR was 90.9% for patients treated with rh-endostatin plus chemotherapy compared with 67.7% for patients treated with chemotherapy alone, indicating that the combination of rh-endostatin with chemotherapy may effectively improve the chance of tumor downstage before surgery. Follow-up study of the patients will provide data as to whether the increased ORR rate can be translated into high PFS and OS. Stratification analysis revealed that premenopausal patients and patients with ECOG sore of zero had higher ORR, indicating that premenopausal women with good performance status may benefit more from rh-endostatin combination therapy.
For patients treated with anthracycline-based neoadjuvant chemotherapy, a higher pCR has been shown to be predictive of improved PFS and OS [16, 26]. In this study, the combination of rh-endostatin with chemotherapy achieved a higher pCR rate (15.2%), but not statistically different from chemotherapy alone (6.5%), which is probably due to the small number of patients enrolled in the current trail. In fact, we are designing a multicenter, prospective, randomized, controlled phase III clinical trial that will include a total of 800 patients to further evaluate the efficacy and safety of rh-endostatin in breast cancer treatment (NCT01479036).
In the present study, the total incidence of adverse events was 81.2% in the rh-endostatin plus chemotherapy group and 79.3% in the chemotherapy alone group. Most of the adverse events were of grade 1 or 2. Grade 3/4 adverse events associated with rh-endostatin included leucopenia, neutropenia, nausea, vomiting, and hand-foot syndrome. Statistical analysis indicated that the addition of rh-endostatin did not increase drug-related toxicities, especially those typically observed in other antiangiogenesis agents such as bevacizumab. A systematic review and meta-analysis reported that the addition of bevacizumab to chemotherapy in MBC patients did increase the risk of left ventricular dysfunction and hemorrhagic events, whereas it was not associated with a significant increase in grade ≥3 arterial or venous thromboembolic events, gastrointestinal perforation, or fatal events . In addition, rh-endostatin exhibited good tolerance, as verified in QOL score questionnaire before and after treatment. However, it should be noted that patients with history of serious heart disease, and with liver or kidney dysfunction were excluded from the trial. The impact of rh-endostatin upon the incidence of adverse events should be further assessed in larger scale trials in future.
Some limitations of the present study have to be considered. Since there is no previous report on rh-endostatin in breast cancer therapy at the neoadjuvant setting, we did not make a pre-planned power calculation. Second, the number of patients enrolled is relatively small, making a multiple factor analysis inappropriate. Thus, we must state here that the subset analyses used in this study were mostly exploratory.
This prospective, randomized, controlled phase II clinical trial demonstrated that the combination of rh-endostatin and DE chemotherapy may improve overall clinical response in patients with stage II or III breast cancer, especially pre-menopausal patients and those having ECOG score of zero, without increasing adverse events. Therefore rh-endostatin can be used as a safe and effective strategy in neoadjuvant treatment of breast cancer.
Jianghao Chen, Qing Yao, Dong Li contributed equally to this work.
This work was supported by grants provided by National Natural Science Foundation of China (No. 81172510, JC; No. 81272899, LW) and Natural Science Foundation of Shaanxi Province (No. 2011 K12-45, JC; No. 2012 K13-02-28, QY).
Part of this work has been reported as General Poster in 47th ASCO. [Wang L, Chen JH, Yao Q, Zhang JL, Wang T, Wang H, Zhou XD, Huan Y, Wang J. Neoadjuvant rh-endostatin, docetaxel and epirubicin for breast cancer: efficacy and safety in a prospective, randomized, phase II study. 2011 ASCO Annual Meeting Proceedings, J Clin Oncol 2011; 29(15 s): 112 s].
JC preformed core biopsies, participated in study design, and drafted the manuscript. QY carried out pathologic and immunohistochemical examination. DL is an independent statistician and was responsible for the statistical analysis and data interpretation. JZ and TW collected clinical data. MY and XZ performed fine needle aspiration and lymph node response evaluation. YH and JW performed radiological examination. LW conceived the study and helped finalize the manuscript. All authors read and approved the final manuscript.


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Trading Deck
Stocks - General
Should you pay attention to what the 'smart money' is buying?
Published: Sept. 10, 2014 at 10:12 a.m. ET
It's that time of year again. Every September, Barron's polls its "all-star team" of Wall Street strategists to get their favorite sector bets, and their best estimates for the S&P 500 and the 10-year Treasury, among other market calls (see "Steaming Ahead").
Let me summarize in words that should surprise no one: They see stocks trading sideways and bond yields rising.
I'm a big believer in taking anything a Wall Street strategist says with a grain of salt.
They are paid to look after the interests of their respective employers, which may be (and generally are) very different from yours and mine. That said, they also tend to be very bright and have access to the best research departments in the world. And in certain situations — such as when they show clear signs of groupthink — their calls can be useful contrarian indicators.
Let's take a look at what Barron's nine big-bank strategists see for the remainder of this year:
Macro call Highest Lowest Average
S&P 500 Year-End 2014 2100 1950 2028
10-Year Treasury Year-End 2014 3.15% 2.50% 2.90%
GDP Growth, 2nd Half of 2014 3.5% 2.5% 3.1%
GDP Growth 2015 3.5% 2.6% 3.0%
For a crowd with a reputation for being permabulls, expectations for the S&P 500 are quite modest. The highest estimate is only about 5% higher from today's level, and the lowest estimate is less than 3% below today's level. In other words, they don't see a major move either way between today and the first of the year.
Interestingly, all nine strategists saw bond yields going higher from here. The average estimate — 3.1% — is within rounding error of where the 10-year started 2014. I should note that, back in December, the consensus was for yields to go sharply higher. The strategists swung and missed on that call, as yields have drifted lower for all of 2014.
On the GDP front, there was a fairly tight range of estimates — 2.5% to 3.5% for the second half of 2014, and 2.6% to 3.5% in 2015.
What conclusions can we reach from this?
Well, to start, I'm not seeing much in the way of independent opinion. There is near unanimity in forecasting for stocks to trade sideways and bond yields to rise. This is a clear sign of herding, and a contrarian warning sign to expect the unexpected. The strategists have consistently been wrong in forecasting a sharp rise in yields.
Given that U.S. yields have fallen even as the Fed has progressed with an aggressive tapering schedule and given that the European Central Bank is about to pick up where the Fed left off with a modified quantitative-easing program of its own, I would expect yields to continue to drift sideways in a range of about 2.2% to 3.2% over the next several years.
I also see signs of herding in the strategists' favorite sectors. Literally all nine strategists listed technology as one of their favorite sectors. There was less consensus on the sectors to avoid, though six of the nine strategists recommended avoiding telecom.
Perhaps the contrarian trade of the next six to 12 months should be to sell or underweight tech and go long telecom and yield-sensitive investments.
Disclaimer: All investments involve risk and various investment strategies will not always be profitable. Past performance does not guarantee future results.
A cheap growth stock? Apple
The shares of Apple Computer (AAPL) have pulled back, along with the overall market as of late. They hit a high of $422 per share five weeks ago, and they are now trading at $363.57. That is a pullback . . .
4 strategies for McDonald's management
Forget about whether $100 silver is possible — how about $1,000?
Try this strategy: One stock per week
Shaking out the weak hands

redpajama_set_name: RedPajamaCommonCrawl


Without relevance, there is no value. Without value, there is no relationship. Without relationship, there is no business. A focus on building relationships is the key to success in business.
In the rapidly changing digital landscape of content production and distribution, it is often confusing how to proceed. Not all content fits all stages of the customer journey. Some business owners get caught chasing the latest trends trying to find the unicorn growth hack that solves all their problems.
What these owners are missing is a strategy that guides their business. That strategy is to design everything you do with relationship building in mind.
Valuable content is the engine that drives your sales funnel. User intelligence helps you create valuable content. The customer journey is where you collect user intelligence. Each piece is integral to growing your relationships.
I call this a relationship engine.
I love building digital products, whether it's a website, a digital sales funnel, an SAAS web app, or an information product. Staying current with what works is easy with my internal projects.
01. WEBSITE DESIGN & DEVELOPMENT.
Website development and design, from a management aspect as well as hands on, has been my craft the longest. My favorite work is building out software platforms that further business growth.
I'm not sure there is another skill that can exponentially increase your growth beyond building successful digital funnels. Using automation, content, and user intelligence, we can build out funnels that build relationships and drive revenue.
Content marketing is the disciplined pursuit of relationships via valuable content creation and promotion. Earn organic traffic naturally with a custom content marketing strategy.
I have had the pleasure of working with some really great people over my 20 year career. Our business relationships have grown into personal friendships. Client service is my number one priority!
If you want your company to succeed and get more clients, Monster studios can do just that …. Becky is the best and I wouldn't work with anyone else. She's also very honest.
I am not good writing reviews, so all can what I say about the job done with my web page is SIMPLY THE BEST. I am happy, and my customers have the right tool to find my business and place their orders.
What's on your mind? Ask away and I will get back to you as soon as I can.


Inspired by American military apparel, Mr & Mrs Italy interprets iconic garments with an Italian flair, transforming them into fresh, modern silhouettes. The collection launched with an update on classic army green parkas, lining them with luxury rabbit, beaver, fox, and mink fur. The label uses handcrafted materials to create covetable ready-to-wear and outerwear essentials.
Inspired by American military apparel, Mr & Mrs Italy interprets iconic garments with an Italian flair, transforming them into fresh, modern silhouettes. The collection updates classic army green parkas, lining them with luxury fur and using handcrafted materials to create covetable outerwear essentials.


1) Bereishis 25 - The Bracha on the Havdalah Candle: Before or After?
2) Noach 25 - V'sain Tal U'Matar - Starting Too Early?
7) Vayeitzei 25 - Davening With A Minyan - Obligation Or Just A Good Idea?
8) Vayishlach 25 - Tefilas Haderech: How Long Of A Trip?
12) Vayechi 25 - Grandfather or Great Grandfather - Who Should Be Sandik?


Mark your calendars for January 8th we're taking workplace safety to the next dimension.
New to Twitter? No problem. Click here for instructions on signing up.
Join us for the launch of our monthly Twitter Chat. Peter Cooke, Safety Specialist with Columbus McKinnon will be our guest safety expert. In addition to traveling the world teaching proper rigging techniques, rigging gear inspection, hoist and crane inspection and maintenance, Peter is well versed in Hazard Communications.
Our first chat is about Hazard Communications because communication is the foundation of any and all safe work environments. We'll be discussing Hazard Communications and the Hazard Communication's Checklist. OSHA regulations change and we want to start and continue the dialogue online to make sure that we're working together to keep manufacturing safe not just for the overhead crane and hoist industry but any industry regulated by OSHA.
We'll keep the conversation going between chats using the same hashtag.
Certified Crane Care Tech Tips is taking safety to the tweets!


Why The Heck Do I Want Social Media For My Business?
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It's best to ideally have an space in your home put apart just for ironing. Baby-free, pet-free, smoke-free. When you start any business you may need to think about what service you could be providing and run by the use of some worst case eventualities. When you've got youngsters, they might determine to be helpful and empty all the baggage out and kind them into colours for you; pets may resolve a pile of freshly ironed sheets and towels is an ideal place to offer starting or wee; no purchasers will want their clean garments returned smelling of smoke. In addition to this, asthmatics will not be able to tolerate stray pet hairs or smoke.
We've all seen the commercials and advertisements for the e-guide or on-line course on flipping homes. The primary principle in each of these, it appears, involves shopping for beneath market. One course even touts knocking on doors and making a low ball supply sufficient instances and somebody will take your bid. Properly, guess what? The first key to making a worthwhile company acquisition is to buy at a lovely price. The funding banks and merger and acquisition companies are engaged to drive up the marketing worth by getting several certified patrons concerned in a easy public sale. Process vulnerabilities is also inside or exterior. The prospect that your manufacturing plant shuts down because of the Asian region the place 90% of that electronic half is produced is hit by a storm was a serious downside a variety of years up to now; whether you resolve it by stocking up on that part or cultivating new suppliers is a selection each group has to make.
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You presumably can interchange this subsequent step with the registration with the BIR. Some firms register first with the BIR when they do not have any transaction yet. Others (which is maybe the bulk) select to register first with the local government the place their business is residing. In any case, earlier than registering with the native authorities (what we title the Metropolis Hall), it is advisable comply first with quite a few necessities (clearances, funds, and so on.). In contrast to the SEC and the BIR, the charge here is not going to be fairly that fixed. The native authorities payment will depend on the prevailing local legal guidelines and the kind of business you're in. That you must get your accountant to have this calculated directly so that you'll understand how a lot you need to pay the native authorities. Once you get your business allow (which is renewed every year), you're ready to start your business.


text:
Time to Innovate for Faster, Smarter Discovery and Clinical Development Cycles
Contributed Commentary by Josh Gluck
August 6, 2020 | We've learned so much living through these unprecedented times. One lesson is the need to mobilize quickly, provide effective testing and contact tracing, and accelerate the development of therapies and vaccines to protect the global community. The issue is not simply one of speed; it's more complex than that. We must also enable smarter development cycles with innovative approaches that provide the most expeditious, cost-effective, and, ultimately, safest path forward.
That can only be done through the power of data: the defining currency in drug discovery and clinical development. We need to be able to leverage more of it, faster, and more completely than ever before to shave time off the drug discovery and development time frame.
Artificial intelligence (AI) is playing a growing role in nearly every phase, from compound identification to clinical trial recruitment to efficacy or toxicity detection during early or later-stage clinical trials. We've only begun to scratch the surface. The next frontier lies in operationalizing AI to ensure rapid iteration and expansion across the enterprise.
What can we do to move faster? Let's start by looking at where AI is having an impact today.
Mining existing research
AI is gaining traction in automating the process of mining scientific research and patient data – saving massive amounts of time and reducing the cost associated with manual research. In addition, researchers are leveraging AI to explore data from thousands of existing drugs and compounds to determine whether they can be repurposed for new therapeutic uses. We already see applications of this in potential treatments for COVID-19, accelerating time to clinical trials, and hopefully, time to market.
Identifying compounds
Researchers are leveraging AI to mine data on various molecules, compare them against desired parameters, and identify the most promising compounds for synthesis and testing. Additional research in this field is emerging, with machine learning (ML) and quantum physics combining to deliver even greater impact. This has a ripple effect in accelerating subsequent stages of drug discovery, with fewer compounds needed for testing and development. One candidate, from British startup Excscientia, took less than a year from conception to being ready for trials.
Improving pharmacovigilance and efficacy
Safety is paramount in drug development and post-market. Pharmacovigilance remains a highly manual and increasingly expensive and complex process as channels for receiving data on potential adverse events continue to grow. Social media platforms are a prime example as they can contain important signals as to potential issues. We're seeing AI technologies leveraged extensively in these areas. A new study by the Drug Information Association and the Tufts Center for the Study of Drug Development found that 57% of pharma and biotech companies are using AI for pharmacovigilance and risk management.
In addition, convolutional neural networking holds promise for optimizing potency and testing for off-target toxicity, as it enables companies like Atomwise to simulate and analyze molecular reactions and predict how they might act. The result is smarter development and identification of hits that provide maximum benefit and minimum adverse effect.
Simulating randomized control trials
The diseases and superbugs we find ourselves fighting today are incredibly sophisticated and complex. Despite massive investment in research and development, only 5 in 5,000 drugs reach market. We must move from correlation to understanding the structure by which a disease operates. For example, GNS Healthcare used AI to process genetic data of patients with Parkinson's and uncover previously unknown mutations that may contribute to faster deterioration. Moreover, the company was able to create 5,000 computer simulations of randomized control trials—comparing a patient's potential response to different drug scenarios. Simulations are a powerful development that ensures not just safety, but also optimizes R&D costs.
Creating a clinical data hub
Even though AI is advancing the drug development cycle with computerized trials, clinical trials with tests in animals and humans remain essential for Food and Drug Administration (FDA) approval. Researchers must document their results at each step—and report fatal or life-threatening suspected adverse events within seven days.
To address growing data requirements and complex data volumes, AI is already proving its usefulness in reducing the administrative burden associated with managing vast data sets associated with clinical trials. AI platforms that analyze biological and clinical data streams from diverse sources and formats—ranging from blood results to imaging—can also accelerate time to insight for investigators.
How organizations can create an infrastructure for AI success—faster
Recent events have underscored the need to move faster to seize the potential of AI technologies and methodologies. And yet, because AI is still a new type of deployment for many organizations, it presents unique challenges. They must consider where data will live, where workloads will run, and how to optimize their infrastructure to power analytics at record-breaking speed. Often, data science teams face operational challenges because they lack the oversight and automation to produce models efficiently, using repeatable processes. This limits the ability to operationalize ML at scale.
To achieve the full benefits of AI and extend into deep learning, organizations must realize a modern data experience and the foundation for it. A modern data experience enables data storage as a service that allows companies to extract maximum value from their vast amounts of data while reducing complexity and expense.
To scale quickly, some organizations are turning to joint ventures to leverage supercomputers. While these partnerships are feasible for well-resourced companies and make sense for short-term projects, many companies would benefit from having their computing power closer to their researchers' fingertips. Data storage as a service makes this possible—allowing organizations to scale up or down quickly and cost effectively based on need. Above all, researchers need storage that is flexible based on usage, whether for mining research, identifying and evaluating compounds, or supporting clinical trials.
The scale of data available for investigators may also vary with each project. This is where smart provisioning becomes especially valuable. AI-based optimization enables life sciences companies to forecast where workloads should run for optimal business impact. It also helps optimize IT spend by forecasting data growth requirements, enabling leaders to make the most of R&D budgets.
Moreover, modern infrastructure must be able to power analytics at record-breaking speeds. Time is of the essence in discovering hits and developing life-saving therapies. To power AI—and faster insights—organizations must deliver low latency, high bandwidth, and maximum density.
AI applications must be supported by straightforward infrastructure, not complex setups. Infrastructure complexity is often the main reason for stalled AI initiatives and uneven adoption of AI for discovery and clinical development. In contrast, a fully integrated stack can accelerate the AI pipeline and avoid the need for intricate configuration and tuning so investigators hit the ground running. Simplicity remains the name of the game; the modern data experience enables researchers to seamlessly transition to a cloud model for maximum agility and improved efficiency at every stage of development.
We need to be able to leverage more AI, faster. The right infrastructure meets this urgency and is operational immediately, without slowing down any projects through downtime. Further, modern infrastructure ensures life sciences corporations remain on the cutting edge with continuous software and hardware innovation to support the latest AI advancements and computing requirements.
Josh Gluck is Vice President of Global Healthcare Technology Strategy at Pure Storage where he is responsible for Pure's healthcare solutions technology strategy, market development, and thought leadership in healthcare. He is also an Adjunct Assistant Professor of Health Policy & Management of NYU's Robert F. Wagner Graduate School of Public Service. He can be reached at jgluck@purestorage.com.


text:
Hamzeh Lan (, also Romanized as Ḩamzeh Lān) is a village in Kani Sur Rural District, Namshir District, Baneh County, Kurdistan Province, Iran. At the 2006 census, its population was 274, in 42 families. The village is populated by Kurds.

References

Towns and villages in Baneh County
Kurdish settlements in Kurdistan Province

redpajama_set_name: RedPajamaWikipedia


How well do you know me? Friendship Quiz!
Find out who knows you best! You must choose a series of questions to answer, then share it with anyone and find out how well if he/she knows about you.
Having a problem with the game? Clear your browser cache and Try Again!
(1) You can begin the quiz by entering your name and tapping 'Start!'. You must then start choosing an answer for the questions provided. You may even consider changing the question by tapping on the 'change question' button. After completing all the questions you can choose to share the link to anyone.
(2) The person with your shared link may then use that and start answering the quiz you just created, finding out how well if he/she knows about you in the end.
(3) Find out who answered your quiz and their score by going to the link you intially created.
You may think you know everything about someone, whether it is your partner or your best friend. But we don't know them completely. Think of this as a friendship quiz.
Make a Quiz, Send it to Your Friends or Post it in your Profile! Ask your friends "how well do you know me?" and find out who knows you best.
Choose a range of questions to even help you with your relationships and transform this online quiz maker into a dating quiz. Does my partner really know me? Quiz your friends and find out! These love tests and personality quizzes help you with your love and relationship issues.
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Discussion in 'Announcements' started by Sadik, Jun 8, 2016.
Announcing the release of PemBer 1.4.0 RC2 available to customers with active licenses.
Since the release of PemBer 1.4.0 RC1, two Bug were discovered. These have been fixed in this release.
This release of PemBer also improves upon the purchase process for logged in members showing them a unified place for purchase of a product.
This page will is accessible to members and allows them to buy with Paypal or Card or charge their existing card.
PemBer 1.4.0 RC2 is available for download from the releases forum.


After an update and dist-upgrade today I get the errors as listed below.
The user `www-data' is already a member of `asterisk'.
Nitech HTS festival voices already installed, no action required.
The connection refused errors seem to resolve themselves and the module in question gets installed.
Are the database errors something to be worried about?
If someone wants me to check logs/errors to determine if this is an issue or not let me know.


Absenteeism from schools. Young girls who don't have access to sanitary pads because of expenses are normally forced to stay at home during 'that time of the month'.
Unhygienic ways of using sanitary pads. Education on personal hygiene is very important for young girls especially in the school environment. Most schoolgirls are faced with the challenge of being absent at school on the days they menstruate in the month, which causes poor work performance at school and low self-esteem in front of their peers. Poor menstrual hygiene can also pose physical health risks.
Limited education about the facts of menstruation as well as fears caused by cultural myths plays a big part in the stigma surrounding menstruation.


Paternity can be established through the issuance of a court order in which the parties typically submit to DNA testing in order to establish the paternity of the child in question.
Unwed parents may sign an Acknowledgement of Paternity which identifies the man as the biological father of the child. Once the Acknowledgement of Paternity document is signed, the biological father's name will be listed on the child's birth certificate which will afford the father parental rights and responsibilities.
There is a legal presumption that a husband who conceives a child during his marriage is the biological father of that child which he may challenge in a Family Court proceeding.
If you are a father, you may wish to establish paternity in order to gain custody of your child or seek visitation rights. As a mother, you may wish to establish paternity so you can seek child support that will help provide for your child. Or, you may wish to disestablish paternity to avoid responsibility for a child that is not yours, or to keep someone from gaining custody of your child who is not the true father. Whatever specific paternity matter you are attempting to resolve, I am confident that I can offer you the information and guidance you need to make the right choices about your case.
Contact a Long Island Fathers' Rights Attorney today!
Resolving a paternity matter may be simple due to the fact that DNA testing can easily prove the biological father, but there are legal matters to address as well. The process of attempting to establish paternity or disprove paternity can be difficult, and it is therefore important to have a competent attorney, such as myself, at your side.
You need a Long Island paternity attorney with experience in this field and the legal knowledge to properly file your claim or assist with any issue that may arise. Contact my offices today!


serving Langenburg, Churchbridge, Bredenbury, Saltcoats and surrounding area is looking for new owners.
Bill and Lynda Johnston are planning to retire on July 31, 2019.
Please spread this information. Otherwise our local newspaper may be closing.


This Review of Garuda Business Class, 777-300ER is from my husband's recent flight from Bali, Indonesia to Tokyo, Narita, about a 7 hour flight. See all of our business class airlines reviews, by airline. Traveling to Bali? See our posts tagged Bali. I booked my husband's award flight with 40,000 Delta miles.
Garuda Business Class has 42 business class seats in a 1-2-1 configuration, with a small business class cabin of 10 seats (rows 6-8) right located right after the first class cabin, and a second larger business class cabin of 7 rows (rows 9-16; there isn't a 13th row, I supposed due to superstition over this being an unlucky number) located after the galley and lavatories and before the economy class cabin.
For a solo traveler, the most desirable seats are the A and K seats that are close to the window, with the table by the aisle, and as such are more private. The best of these seats are 6A and 6K, as they are in the mini business class cabin right behind first class, and not by the galleys or lavatories. 11A, 11K, 14A and 14K would also be good solo seats, if 6A and 6K are already taken.
For couples, the best seats are 6E and 6F, in the mini cabin; otherwise, if those are taken, 11E/11F and 14E/14F would also be good seats.
considering the overnight flight and full business class cabin.
contoured to fit someone much smaller than I am. This seat was curved in all the wrong places for me.
some privacy, with a narrow entrance (about 12 inches wide) to the aisle.
landing. In retrospect, this seemed odd since there was no turbulence at all for the last 1-2 hours prior to landing, but there was turbulence when breakfast was served.
I started with orange juice and some rolls, which were not very fresh.
I then had some breakfast cereal and fruit, which was much better.
The omelette, with sausage and potatoes, was rather good, although the omelette was a tad oily.
serviceable. I watched the Shape of Water, which did seem overrated.
did allow me to get some good hours of sleep. I was glad I was in seat 6A, in the mini cabin, which was very quiet, with only 10 seats, and recommend selecting this seat if available.
I can't say I was impressed by the catering/food on board, and do wish I hadn't been woken up so early, since there seemed to have been ample time without turbulence prior to landing. I was also surprised that there was no amenity kit or sleep mask offered.
If you've flown Garuda Business Class recently, what was your experience?
3 Comments on "Review: Garuda Business Class, 777-300ER"
My wife and I flew Garuda Business Class Narita – Bali on this plane last year. It was a daytime flight and we enjoyed our experience. The quality of service and food for me personally was comparable to CX and JAL Business Class which I have flown multiple times.
Glad to see a Garuda business class review. The blogging world has been all over their first class, but everyones left this out. Thanks for the review.
As 747always mentions Garuda 1st is a widely acclaimed product. I certainly expect that the ground experience for business class was not nearly as coddled, but otherwise how did it compare to Garuda 1st?


You know it really must be a regional thing. That song was big here.
Darn, I even gave the first line thinking that would give it away for sure.
Martha the link to the entire album bt Leisure Process is in The "Obscure" and as posted by '82 in the New Wave/'80s Discussion threads! "Casg Flow, where did our love go..." one of my faves is Cash Flow song.
Thanks, Glok! I'll go grab it!
<br>Thanks, Glok! I'll go grab it!
Somewhere between the soul and soft machine, is where I find myself again.
Get no answer at all"


In part 3, you'll make further adjustments to the Catapult's dynamics to fine tune the rock launch. And construct the towers and walls that make up the castle.
In the second part of the series, you'll finish modeling the remaining parts of the scarf. You'll then move on to create the Snowman's mittens and arms.


The dog is one of six to die in the first recorded cases in the UK since May.
Staffordshire dog owners are being warned to be vigilant after a dog in the county died from Alabama Rot.
The animal, which lived in Cannock, died from the condition earlier this month along with five other dogs across the UK.
The six deaths are the first recorded cases of the disease since May 2017 - when specialists from across the country gathered to discuss ongoing research into the condition.
Scientists now believe the condition may be seasonal - with most cases occurring between November and April.
It is unknown whereabouts in Cannock the animal contracted the disease.
A total of 109 dogs across 30 countries, including Staffordshire and Cheshire, have died from Alabama Rot since it was first detected in the UK in 2012.
In Staffordshire disease has previously been recorded in Dimmingsdale, near Oakamoor in the Staffordshire Moorlands, in October 2015 and in Penkhull in February 2017.
In South Cheshire cases have been reported in Nantwich in February 2015 and Crewe in March 2017 according to data from Anderson Moores.
The disease, which as the name suggests originates in the American state of Alabama, can target any dog - with treatment only successful in around 20 per cent of cases.
"If a dog becomes affected, the best chance of recovery lies with early and intensive veterinary care at a specialist facility such as Anderson Moores. Such treatment has resulted in some dogs successfully recovering from the condition.
Skin lesions are one noticeable sign of early onset of the disease, according to our sister paper the Leicester Mercury.


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text:
International Students and Net Migration - Why Students should be counted as net migrants
Immigration by Students: MW 265
1. Genuine university students are welcome and should be encouraged. However, excluding students from net migration would achieve nothing except to destroy public confidence in the government's immigration policy. No other leading country does so.
2. Universities UK have called on the government to remove international university students from net migration statistics for "policy purposes". This paper argues for their retention.
The case against exclusion
3. The international (UN) definition of a migrant is a "person who moves to a country other than that of his or her usual residence for a period of at least a year"[1]. If the UK alone were to use a different definition our statistics would be inconsistent with other international statistics. The USA, Australia and Canada, regardless of how they classify students for domestic purposes, all include international students in their net migration calculations. The Table at Annex A compares the visa regime in the UK with the regimes in these three countries.
4. More importantly, the most recent estimates of international migration show that study remains the most common reason for migrating to the UK – about a quarter of a million people (excluding dependants) came to Britain to study in the year to September 2011[2]. Given that students form such a large component of immigration, their exclusion would destroy the credibility of the government's immigration pledge – a commitment made in response to widespread and strong opposition to the mass immigration experienced over the last ten years.
5. Furthermore, students are counted out (although not currently separately identified) as they leave as well as when they arrive, so there is no reason to exclude them from the statistics. Clearly, if they were to leave at the same rate as that at which they arrived, there would be no addition to net migration. In practice, Home Office research suggests that some 20% of students are still legally present after five years and many of those will stay on indefinitely by reason of marriage or employment. This does not, however, mean that the rest have left the UK. Unlike the US and Australia the UK still has no exit checks.
6. It is highly relevant that there are important differences between the immigration and border controls systems operated by the UK and by our two key competitor countries – the United States and Australia. They both interview student applicants while Britain has not systematically interviewed students since it introduced the Points Based System (PBS) in 2008. A student applicant to the UK merely has to have a Confirmation of Acceptance to Study issued by the educational establishment to which the student has applied, to demonstrate sufficient funds and to provide written evidence of sufficient English language attainment. If these criteria are met, the applicant is granted a visa. Student applicants to the UK are not assessed to ensure that they are both genuine and intend to return home – a test applied vigorously by competitor countries. This has clearly not prevented them from attracting a large number of students. Indeed, an unpublished report from the British Council found that, in respect of Australia, there was no correlation between tougher immigration controls and numbers of applications – demonstrating that genuine students are not deterred by interviews, increased paperwork and tougher requirements.[3]
7. It is also the case that both the United States and Australia operate a system of embarkation controls on entry and exit. Thus the authorities know whether a student has left the country or not – a significant deterrent to overstaying. In Britain there are no embarkation controls and e-borders is not yet fully operational. Students may therefore believe that they can overstay with impunity.
8. These factors may explain why there is clear evidence that there has been significant abuse of the PBS by bogus students with a consequent addition to net migration. Following its introduction – a system that removed all discretion from Entry Clearance Officers (ECO's) – student applicants to the UK increased by 30% in the first year, including significant growth in numbers from the Indian sub-continent. This was borne out by the report from the National Audit Office which found that, in the first year of the PBS, up to 50,000 students may have entered the UK to work rather than to study[4].
9. As part of its efforts to reduce net migration the government has targeted bogus students and colleges. More than 450 colleges have had their licences to enrol international students withdrawn since the Home Office introduced a stricter regime of compliance and accreditation. This is expected to contribute to a fall in student immigration without affecting genuine university students.
10. There is a requirement to continue to tackle the extensive abuse in the student system without impacting on genuine university students. Improved surveillance of colleges is a useful start. Alongside this should be a significant increase in appropriate enforcement action to reduce the likelihood of overstaying. However, once bogus students have arrived in Britain, the cost of removing them is very high (roughly £26,000 each). What is needed is a return to the system of interviews, focussed on countries of immigration concern. The purpose of these interviews would be to introduce an element of judgement as to whether the applicant is a genuine student and whether he or she is likely to return home at the end of the course. The present box ticking system has demonstrably failed.
11. It is also important to have a much clearer idea of the true impact of international students on net migration. At present there is no direct measure as e-borders is far from complete. Nor is there any survey evidence from the International Passenger Survey (IPS). Departing migrants have been asked the purpose of their journey so those who came as students and were going home to seek work were classed as workers; as a result it has not been possible to distinguish departing students from departing workers. According to the IPS, 1.5 million students have, over the past ten years, been recorded as arriving for more than one year but the government have not the slightest ideas how many have actually left. It is hoped that an improved questionnaire asking departing migrants their original purpose for entering the UK will produce some initial results from 2012.
12. Genuine students are, of course, to be welcomed – they come to study, spend money and add to the richness of campus life. If they return home, they do not add to net migration. Bogus students however add to net migration and call into question the whole system of border control. It is in everyone's interest that bogus students should be prevented from arriving and that there should be no question of manipulating the statistics in respect of those who are genuine.
13. Universities UK wish to see foreign students taken out of the migration statistics unless and until they stay on legally either to work or marry. They also want to see a significant expansion in numbers. The implications of these proposals need closer examination.
14. Foreign students fall into four main categories:
Bogus students
Those that intend from the outset to remain in the UK. Much firmer measures are needed to combat this abuse, notably the re-introduction of interviews, in line with our main competitors (para 10 above).
Genuine students who return home
No problems if they do return at their end of their courses
Genuine students who stay on legally
A number will stay on to work or marry. This is a natural, indeed welcome, aspect of overseas students but the numbers are significant. Universities UK have accepted the Home Office estimate that they amount to about 20%. With annual arrivals of foreign students running at about 250,000, that flow would add about 50,000 a year to net migration. There is therefore a significant relationship between the scale of overseas students and net migration.
Students who arrive legally but stay illegally
Such students usually stay on to work so as to pay off their debts and later to send money home. They add to the illegal population, take jobs from young British workers and add to the cost of public services. Those from poorer countries are much more likely to overstay. Last year 125,000 from such countries were granted visas; if, in addition to the 20% who are likely to stay on legally, a further 20% were to stay illegally this would add 25,000 to the figure in sub paragraph c) above.
15. The universities UK proposal that only those who stay legally should be counted fails to address those who fall into categories (a) and (d). Indeed, as there are still no checks on departure, there is no way of knowing how many students have, in fact, stayed. To suggest that they be removed "for policy purposes" makes no sense when some 75,000 stay on every year, legally or otherwise, and the central purpose of the policy is to get the overall numbers down to an acceptable level. As for the implication that university level students be treated separately for statistical purposes, that is clearly impracticable. Some students come for foundation courses before going on to universities. Others go to nearly 500 institutions who offer degrees, often in association with the universities themselves.
Foreign exchange earnings
16. Universities UK state that foreign students contributed nearly £8 billion to the foreign exchange earnings of the UK in 2009. This was about 2% of the UK's total foreign exchange earnings (£400 billion) in the same year. However, nobody is remotely suggesting that all foreign students be banned. A more relevant figure is that a 10% change in the number of foreign students might change the UK's foreign exchange earnings by about 0.2%. This takes no account of the fact that any such earnings will be offset by money that former students are likely to send home over many years.
17. This paper suggests that, were students to be removed from the net migration calculation, the statistics would be distorting reality. If the public are to have faith in the immigration statistics, excluding a high proportion of those who enter (and stay in) the UK would undermine the credibility of the entire system – especially as no other major country does so. There is more than enough mistrust in this field without adding to it further.
Comparison of visa regimes for international students
UK USA Australia Canada
Interviews for student visa applicants No Yes Yes Yes
Test of intention to return after study No Yes Yes Yes
Checks on departure No Yes Yes No
Out of country appeals by students Yes No No No
Inclusion of students in net migration statistics Yes Yes Yes Yes
United Nations, URL: http://unstats.un.org/unsd/demographic/sconcerns/migration/migrmethods.htm
ONS Long Term International Migration Estimates http://www.ons.gov.uk/ons/publications/re-reference-tables.html
Michael Knight, Strategic Review of the Student Visa Program 2011, June 2011, URL: http://www.immi.gov.au/students/_pdf/2011-knight-review.pdf
http://www.nao.org.uk/idoc.ashx
Recent Immigration by Students Papers
Why international students must not be removed fro…
[MW441 - 28 February 2018]
[MW431 - 18 December 2017]
How many students have been granted settlement in …


Has The CW found its next great female heroine?
The network has acquired The Outpost, a 10-episode fantasy drama from Arrowstorm and Electric Entertainment, TVLine has learned. The series centers around Talon (Ash vs. Evil Dead's Jessica Green), the last surviving member of a race known as the Blackbloods.
Years after her entire village is destroyed by a gang of brutal mercenaries, Talon travels to a lawless fortress on the edge of the civilized world, as she tracks the killers of her family. On her journey to this outpost, Talon discovers she possesses a mysterious supernatural power that she must learn to control in order to save herself, and defend the world against a fanatical religious dictator.
The Outpost — which hails from executive producers Dean Devlin (Stargate), Jonathan Glassner (Stargate SG-1), Jason Faller and Kynan Griffin — also stars Jake Stormoen, Imogen Waterhouse, Andrew Howard, Anand Desai-Barochia and Robyn Malcolm.
A U.S. premiere date will be announced at a later time. Outside of the States, The Outpost will premiere on Syfy channels in the UK, France, Spain, Portugal, Germany, Latin America, Poland, the Balkans, Middle East, Africa and Australia.
Your thoughts on The Outpost? Drop 'em in a comment below.


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Austin Says DOD Must Increase Efforts to Destigmatize Mental Health Care > U.S. Department of Defense > Defense Department News
Both the White House and the Defense Department, said Secretary of Defense Lloyd J. Austin III, have made taking care of military families a priority. Included in that "sacred obligation," he said, is an increased commitment to providing support to families who have lost a service member and destigmatizing mental health care.
"This is a national commitment, and it's on all of us," he said. "That means working alongside our friends at the VA [Department of Veterans Affairs]. That means working with lawmakers here in Washington and in state and local governments. And that means being good partners with community organizations big and small."
Austin spoke May 28 during the National Military Survivor Seminar and Good Grief Camp's banquet in Arlington, Virginia. The 28th annual event was sponsored by the Tragedy Assistance Program for Survivors.
The secretary explained some of the challenges faced by military families and their loved ones who serve — all challenges DOD can help with; one challenge involves mental health care.
"It … means redoubling our efforts to reduce the stigmas on getting help and to lower the barriers and increase the access to mental health care," Austin said. "We continue our critically important work to prevent suicide within our military community and our veteran family. You have heard me say this before, and I intend to keep on saying it: mental health is health, period."
The secretary also said DOD must do more to support families who have lost a service member.
"We've got to make sure that we're doing everything we can to support those who have lost loved ones," he said. "We've got to do more to help our newly bereaved families on every level, [from] finding comfort to figuring out benefits. We know how heavy that load can be. We also have to find more ways to stand together and do whatever we can to make the load even a bit lighter."
The Tragedy Assistance Program for Survivors provides care and assistance to families who are grieving the loss of a family member who served in the military.
TAPS is one of the organizations, Austin said, that is helping DOD meet its obligation to take care of military families.
"Last year this organization connected with more than 9,000 newly bereaved family members … and to help on some of the worst days that anyone can go through," Austin said. "You've taken families to ball games so that they can meet one another. You've helped thousands with your training programs on grief, trauma and suicide prevention. You've provided space to support children and teenagers going through unbearable loss, and you've given people new hope and a strong community that they can rely on."
The TAPS organization, Austin said, makes a difference every day within the military community.
"It's moving, it's important, and it is inspiring," he said. "Thank you for all of your hard work."
Austin also noted this is the first Memorial Day to follow the U.S. withdrawal from Afghanistan.
"This year, I am especially mindful that we're observing the first Memorial Day since the end of America's longest war, and we remember the 2,461 American service members and personnel who fell in Afghanistan serving their country," he said. "For surviving family members, we know that grief is with you every day and not just on Memorial Day. We know that, after losing a loved one, it can feel like time grinds to a halt."


This video shows the difference in stopping distances between 30mph and 35mph: 21 feet.
The difference in stopping distance between 20mph and 30mph is 35 feet! If a child runs out 40 feet in front of you, at 20mph you would just stop in time. At 30mph you would hit them still doing 27mph – the equivalent impact speed of dropping them from a 3rd storey window.
The 20mph City Conference from Rod King on Vimeo.


Puerto Rico encountered another roadblock in its efforts to resolve its looming debt crisis on July 6, 2015, when the U.S. Court of Appeals for the First Circuit affirmed the decision of the District of Puerto Rico that Puerto Rico's Debt Enforcement and Recovery Act (the "Recovery Act") is unconstitutional and permanently enjoined its enforcement.1 The Recovery Act, enacted in June 2014, created a bankruptcy-like regime through which select Puerto Rican public corporations could restructure their debt obligations without unanimous creditor consent. Like the district court, the First Circuit concluded that the Recovery Act was preempted in its entirety by Section 903(1) of the U.S. Bankruptcy Code, which prohibits "States" (including Puerto Rico) from enacting laws that bind non-consenting creditors to the terms of a debt restructuring. Unlike the district court, the First Circuit did not address whether the law violated the Constitution's Contract Clause.
The First Circuit decision was handed down not long after the much anticipated Krueger report—a white paper commissioned by Puerto Rico's administration that addresses Puerto Rico's financial situation—indicated that Puerto Rico's financial condition was worse than previously believed and is unlikely to be cured without a debt restructuring. In light of this report, and concurrently with Puerto Rico's appeal to the Supreme Court, Puerto Rico is redoubling its efforts to obtain congressional support for an extension of chapter 9 of the Bankruptcy Code. Even if Puerto Rico secures chapter 9 protection, however, a chapter 9 filing will not be a panacea for its debt crisis as the island's constitutionally protected government obligation ("GO") bonds would not be addressed and obligations of the deeply troubled Government Development Bank (the "GDB") would possibly fall outside chapter 9's purview.
As Puerto Rico presses its Recovery Act and pursues chapter 9, the Constitution's Contract Clause continues to loom as a potential legal barrier to any less-than-consensual restructuring. While the First Circuit skirted a Contract Clause analysis, the district court's decision regarding the Recovery Act was a clear win for bondholders on Contract Clause grounds. Whether recent efforts by Puerto Rico or the Krueger report will tip the balance toward Puerto Rico may be the next legal battle in this ongoing situation.
Though significant, this decision was not particularly surprising to those closely following the Puerto Rico debt crisis. Indeed, when the constitutionality of the Recovery Act was first challenged by bondholders of Puerto Rico Electric Power Authority—one of the public corporations the Recovery Act sought to protect—O'Melveny issued a client alert analyzing the serious preemption and other constitutional issues presented by the Recovery Act.
The primary issue before the First Circuit was whether Section 903(1) of the Bankruptcy Code preempts Puerto Rico from enacting its own municipal bankruptcy law. Section 903(1) expressly prohibits "states" from enacting their own laws. The question here then turned on whether Puerto Rico is a state under the Bankruptcy Code. "State" is generally defined to include Puerto Rico, "except" for the purpose of "defining" a municipal debtor under Section 109(c) of the Bankruptcy Code.2 Based on the plain language of these provisions, the majority of the First Circuit panel concluded that Section 903(1) does apply to Puerto Rico and, as a result, precludes passage of laws like the Recovery Act.
Looking Ahead: Is Chapter 9 a Solution?
The First Circuit decision thus puts mounting pressure on Congress to act. The only tactic Congress has considered thus far is expanding chapter 9's protections to Puerto Rico. Prior to the court's decision, congressional legislation that would allow Puerto Rico's municipalities to commence proceedings under chapter 9 was pending, introduced by Resident Commissioner of Puerto Rico, Representative Pedro R. Pierluisi, in February 2015.5 However, House Judiciary Committee leaders have not shown support for the proposed law, arguing that chapter 9 will not, on its own, resolve Puerto Rico's financial crisis and instead are calling for a more holistic congressional response.6 Still, several Democratic-party leaders, including Hillary Clinton, have ramped up pressure on Congress to reopen chapter 9 to Puerto Rico's municipalities, especially following the release of the Krueger report.
What is left out of this political debate is the two tranches of debt that will not necessarily be addressed by chapter 9—the constitutionally guaranteed GO-bond debt and the GDB debt. As noted above, the GO-bond debt is outside the purview of chapter 9 because that debt belongs to Puerto Rico, not one of its municipalities. The GDB debt may also fall outside bankruptcy laws, since it is uncertain whether chapter 9 could even reach the GDB. While the Bankruptcy Code explicitly prohibits banks from seeking chapter 7 or chapter 11 relief, there is no such express prohibition in chapter 9. However, if a court finds the GDB to be a bank and also that it would thwart the purpose of the statute to permit a bank to file for bankruptcy protection, the plain reading of the statute could be challenged. Thus, whether the GDB is eligible to file under chapter 9, if such protection is even extended to the Commonwealth and its municipalities, will become a matter of statutory interpretation, unless it is expressly addressed by the enacting statute.
If Puerto Rico is unable to obtain eligibility for chapter 9—and to some extent, even if it is—Puerto Rico will continue to face constitutional challenges to its actions. One lesson learned through the district court's analysis of the Recovery Act challenge is that if the Commonwealth's solution is dependent on the enactment of some statutory measure, one issue that will be at the forefront is whether that path is consistent with the U.S. Constitution's Contract Clause. Though the First Circuit found it unnecessary to reach the Contracts Clause issue, the district court held that the claim that the Recovery Act violates the Contracts Clause was at least plausible enough to survive a motion to dismiss. The district court's analysis informs how a court may approach other measures the Commonwealth may pursue (e.g., a temporary moratorium on public debt, as discussed below). But the real question is whether, as Puerto Rico has asserted, its recent actions and the Krueger Report shift that analysis.
In connection with the First Circuit appeal, Puerto Rico took the position that the Krueger Report affirmed that the Commonwealth lacks the legislative tools necessary for restructuring its public debt burden, which is driven, at least in part, by its public enterprises. The report noted that supply-side factors, such as its low employment rate, severely impact the Commonwealth's financial state. While the report directs Puerto Rico to a comprehensive approach, it suggests that a debt restructuring is a key element for a resolution.
One measure that Governor Padilla has proposed in an effort to stave off a fiscal crisis is a multi-year repayment moratorium, although he has not yet provided specifics on such a plan. Though such a measure, at first blush, may seem to meet the necessary prong of "reasonable and necessary," the same could arguably have been said regarding the Recovery Act. Yet, with the Recovery Act, the district court expressed skepticism of the necessity of measures that seek to avoid debt obligation as opposed to looking, instead, to revenue-raising reforms such as spending cuts and tax reform. Whether the Krueger report's implicit assumption that a debt restructuring is required would affect this analysis is unclear. But imposing a moratorium on repayment out of the gate could be viewed as a rash reaction, especially if enacted prior to exploring less extreme measures, particularly from among the myriad reforms proposed by the Krueger report.
For now, the Commonwealth is endeavoring to avoid litigation and to attempt a consensual restructuring. Following the first meeting of the governor's working group, GDB president Melba Acosta said that the government looks to negotiate payment terms and propose the GDB notes exchange, not seek cuts to principal or similar measures as was originally feared. In the weeks, months, and years ahead, the GDB and GDB bonds will be central to initial restructuring efforts and will likely be the bellwether for future restructuring efforts. In the first meeting with the bondholder group, on July 13, Acosta noted that she expects all parties, from creditors to government employees, to shoulder the burden, while noting that the Commonwealth is not seeking a bailout from the federal government. Nevertheless, with the number of debt issuers, their various rights, and the holdout problem present in any restructuring, it is likely that Puerto Rico will again find itself litigating key constitutional issues.
 Franklin Cal. Tax-Free Trust v. Puerto Rico, Case Nos. 15-1218, 15-1221, 15-1271, 15-1272, slip. op. at 4 (1st Cir. July 6, 2015).
 Section 101(40) of the Bankruptcy Code defines "municipality" as a "political subdivision or public agency or instrumentality of the state." 11 U.S.C.§ 101(40).
 Franklin, slip op. at 31.
 See Puerto Rico Chapter 9 Uniformity Act of 2015, H.R. 870, 114th Cong. (2015-2016).
 Press Release, Goodlatte and Marino Statement on Recent Developments Regarding Puerto Rico (July 8, 2015), http://www.judiciary.house.gov/index.cfm/2015/7/goodlatte-and-marino-statement-on-recent-developments-regarding-puerto-rico.
 U.S. Trust Co. v. New Jersey, 431 U.S. 1, 25 (1977).
 Allied Structural Steel Co. v. Spannaus, 438 U.S. 234, 243 (1978).
This memorandum is a summary for general information and discussion only and may be considered an advertisement for certain purposes. It is not a full analysis of the matters presented, may not be relied upon as legal advice, and does not purport to represent the views of our clients or the Firm. Suzzanne Uhland, an O'Melveny partner licensed to practice law in California, George Davis, an O'Melveny partner licensed to practice law in New York, Jonathan Hacker, an O'Melveny partner licensed to practice law in Maryland and Washington, D.C., and Eric Richards, an O'Melveny partner licensed to practice law in California, contributed to the content of this newsletter. The views expressed in this newsletter are the views of the authors except as otherwise noted.