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Publications (156)511.3 Total impact
Conference Paper: Osseous side effects on the growing skeleton exerted by tyrosine kinase inhibitor treatment: data observed in pediatric patients with chronic myeloid leukemia in comparison to a juvenile rat model[Show abstract] [Hide abstract]
ABSTRACT: Background: The tyrosine kinase inhibitor (TKI) imatinib is applied as front-line treatment in adult and pediatric patients with chronic myeloid leukemia (CML) in order to selectively inhibit the causative oncogenic BCR-ABL1 tyrosine kinase. However, TKIs exhibit off-target effects on further kinases involved in the regulation of bone metabolism. As consequence, pediatric patients display longitudinal growth retardation while on imatinib treatment. As CML is a rare disease in children, growth experiences are limited so far (Millot F 2009 Blood; Shima H 2011 Pediatrics). Therefore, we examined longitudinal growth in a pediatric CML cohort and also established a juvenile rat model to investigate side effects of long-term TKI exposure on the growing skeleton. Methods: 102 CML patients (54♂/48♀) receiving upfront imatinib were enrolled in growth analysis using height standard deviation scores (SDS). The animal model comprises male Wistar rats which starting at the age of 4 weeks (w) were continuously or intermittently exposed to TKI at varying dosages over 10 w. After defined time intervals of exposure (after 2w, prepubertal stage; 4w, pubertal stage; 10w, postpubertal stage, respectively), rats were sacrificed and bone parameters and osseous metabolism were investigated. Results: A mean decrease in height of 0.48 SDS per year (y) during the first 2 years of imatinib treatment was observed, with prepubertal patients being more severely affected (-0.75 SDS/y) compared to pubertal teenagers (-0.02 SDS/y). The juvenile animal model demonstrated altered osseous parameters (bone length, trabecular BMD, bone strength) predominantly in long bones compared to vertebrae. Dose-dependently decreased Osteocalcin- and TRAP-serum levels were observed. Intermittent treatment minimized osseous and biochemical changes. Conclusion: Growth retardation is a significant adverse effect of TKI treatment in pediatric patients, which could be uniformly modeled in juvenile rats. In addition, high-dose, long-term TKI exposure in rats predicts an increased fracture risk. Skeletal side effects were reduced by intermittent treatment thus possibly reflecting a new therapeutic option. Ongoing investigations on next-generation TKI revealed identical osseous alterations with dasatinib, whereas bosutinib exhibited milder changes. Presently, TKI administration is considered a life-long treatment thus requiring regular monitoring of skeletal side effects under long-term exposure. Acknowledgement: Funded by DFG-grant SU122-3/1. Disclosure: The authors declared no competing interests.7th International Conference on Children's Bone Health, Salzburg, Austria; 06/2015
Article: Impact of Long-Term Exposure to the Tyrosine Kinase Inhibitor Imatinib on the Skeleton of Growing Rats[Show abstract] [Hide abstract]
ABSTRACT: The tyrosine kinase (TK) inhibitor imatinib provides a highly effective therapy for chronic myeloid leukemia (CML) via inhibition of the oncogenic TK BCR-ABL1. However, off-target TKs like platelet-derived growth factor receptors (PDGF-R) and colony-stimulating factor-1 receptor (c-fms), involved in bone remodeling, are also inhibited. Thus, pediatric patients with CML on imatinib exhibit altered bone metabolism, leading to linear growth failure. As TKI treatment might be necessary for a lifetime, long-term effects exerted on bone in children are of major concern. Therefore, we studied the skeletal long-term effects of continuous and intermittent imatinib exposure in a juvenile rat model. Four-weeks-old male Wistar rats were chronically exposed to imatinib via drinking water over a period of 10 weeks. Animals were exposed to a standard and high imatinib dosage continuously and to the high imatinib dose intermittently. Bone mass and strength were assessed using pQCT, micro-computed tomography (μCT), and biomechanical testing at the prepubertal, pubertal, and postpubertal age. Bone length and vertebral height as well as biochemical markers of bone turnover were analyzed. Femoral and tibial bone length were dose-dependently reduced by up to 24% (p<0.0001), femoral and tibial trabecular bone mass density (BMD) were reduced by up to 25% (p<0.01), and femoral breaking strength was lowered by up to 20% (p<0.05). Intermittent exposure mitigated these skeletal effects. Long-term exposure resulted in reduced vertebral height by 15% and lower trabecular BMD by 5%. Skeletal changes were associated with suppressed serum osteocalcin (p<0.01) and non-significantly elevated serum CTX-I and PINP levels. In conclusion, imatinib mainly impaired longitudinal growth of long bones rather than the vertebrae of growing rats. Interestingly, intermittent imatinib exposure has less skeletal side effects, which may be beneficial in pediatric patients taking imatinib.PLoS ONE 06/2015; 10(6):e0131192. DOI:10.1371/journal.pone.0131192. · 3.23 Impact Factor
Conference Paper: Impaired Longitudinal Growth by Imatinib (IMA) in Pediatric Patients with Chronic Myeloid Leukemia (CML).[Show abstract] [Hide abstract]
ABSTRACT: Objectives: The tyrosine kinase inhibitor (TKI) IMA has been licensed for treatment of CML in pediatric patients in the year 2003. IMA inhibits the oncogenic BCR-ABL tyrosine kinase causing CML, but is also well known for its inhibitory "off-target" effects on bone metabolism resulting in disturbed bone remodeling. This leads to longitudinal growth impairment in not outgrown individuals. In addition, IMA treatment exerts further "off-target" effects by disrupting the growth hormone:IGF-I axis which may aggravate bone growth impairment. The pediatric trial CML-PAED II starting in 2006 recruits approx. 15 pediatric patients with CML annually and as of today comprises the largest pediatric CML cohort on prospective TKI treatment. In this cohort we examined the alteration of bone growth depending on sex, age, and pubertal stage at start of IMA treatment. Methods: 102 CML patients (54 male / 48 female; median age 12 years, range: 1-18 years) receiving IMA as upfront treatment in participating centers in Germany and neighboring countries were enrolled retrospectively into this analysis. During IMA treatment body height and serum bone metabolic parameters were assessed in three month intervals. Height standard deviation scores (SDS) were derived from WHO-AnthroPlus software (version 1.04), a global tool providing normal range values of growth from birth till the age of 19 years. Results: In comparison to mean height SDS at diagnosis a mean decrease of 0.48 SDS per year was observed in the total cohort during the first two years on treatment. Growth impairment was more pronounced in prepubertal patients (27/102 patients; age: <10 years) with a mean reduction of 0.75 SDS per year compared to postpubertal teenagers (29/102 patients; age: >14 years) with a mean reduction in height of 0.02 SDS per year. Discussion: Longitudinal growth impairment is a significant adverse effect of IMA in pediatric patients with CML, affecting predominantly prepubertal children. Today, TKI administration is considered a decades-long treatment thus requiring regular monitoring of skeletal side effects under long-term exposure.7th Midsummer Meeting on Pediatric Hematology, Oncology and Stem Cell Transplantation, Liberec, Czech Republic; 06/2015
- 7th Midsummer Meeting on Pediatric Hematology, Oncology and Stem Cell Transplantation, Liberec, Czech Republic; 06/2015
Conference Paper: Influence of Long-term Tyrosine Kinase Inhibitor Exposure on Cell Counts, Proliferation, and Gene Expression of Spermatogenesis in Juvenile Rat Testes.[Show abstract] [Hide abstract]
ABSTRACT: Background: In pediatric patients suffering from chronic myeloid leukemia (CML) long-term tyrosine kinase inhibitor (TKI) treatment exposes several off-target side effects. TKIs inhibit c-kit and platelet derived growth factor receptor (PDGFR) which in testes are essentially required for spermatogenesis. The influence of TKI long-term treatment on spermatogenesis in pediatric patients with CML is not fully understood. Therefore, we studied testicular tissue in juvenile rats following TKI exposure in a time and dose dependent fashion. Methods: Juvenile, still growing Wistar rats (age: 4 weeks (w)) were exposed for 10 w to imatinib (IMA) or dasatinib (DASA) at different dosages (low dose [LD], high dose [HD], intermittently high dose [ID]). Prepubertal (age: 6 w), pubertal (8 w), and postpubertal (14 w) total testis weight as well as cellularity (spermatogonia, spermatocytes, spermatids, Ki-67 positive cells) in microscopic tubules cross section were evaluated after IMA treatment. Expression of genes involved in spermatogenesis comprising SCF, c-kit and PDGF-R α/β was studied under DASA exposure. Results: Overall, 64 and 40 testes specimen were analyzed for IMA and DASA, respectively. Testis weight was not influenced by any TKI exposure. Compared to non-exposed controls, spermatogenic cell counts were significantly decreased following IMA HD-exposure whereas LD- and ID-exposure attenuated this finding. However, cell proliferation investigated by Ki-67 expression was significantly lowered at all applied IMA doses. Long-term DASA treatment after 10 w at LD, HD and ID, respectively, resulted in significantly reduced gene expression of SCF, c-kit and PDGF-R α/β. Gene expression of PDGF-A was significantly decreased in HD and ID but not LD, whereas PDGF-B postpubertally showed no significant reduction. Conclusion: Long-term TKI exposure resulted in reduced progenitor cell proliferation of spermatogenesis dose-dependently. Thus, - at least in not yet outgrown rats - a long-term negative effect of chronic TKI exposure on spermatogenesis cannot be denied.7th Midsummer Meeting on Pediatric Hematology, Oncology and Stem Cell Transplantation.; 06/2015
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ABSTRACT: Background: Application of DA in adults with CML may lead to adverse cardiac effects (pleural & pericardial effusion, abnormal heart rate, organ hypertrophy). Understanding underlying mechanisms is crucial for the application of DA in pediatrics. Methods: DA was administered chronically [either standard (SD) or high dose (HD)) or intermittently HD (3 days "on", 4 days "off"] via the drinking water to 4 week (w) old male rats for 10 w. Rats underwent regular ECG and cardiac ultrasound followed by necropsy to investigate heart weight. Results: Dose independently, heart weight increased in SD and HD after 2 w, 4 w, and 10 w exposure. Cardiac ejection fraction (EF) and fractional shortening (FS) was unaltered following short-term application but decreased after 10 w on HD. Concordant reduction of EF and FS following both SD and intermittent HD treatment points to a dose-dependent impairment of cardiac development. Conclusion: Cardiac parameters seem less affected by short term application of DA while long-term exposure results in development of cardiac insufficiency. However, intermittent application allows recovery of EF and FS during 10 w of treatment.Annual Meeting of the Kind-Philipp-Foundation for Leukemia Research, Wilsede, Lüneburger Heide, Germany; 06/2015
Conference Paper: Long-term imatinib treatment reduces spermatogenic cell proliferation in juvenile rat testes[Show abstract] [Hide abstract]
ABSTRACT: Background: Long-term tyrosine kinase inhibitor (TKI) "targeted" treatment in pediatric patients with chronic myeloic leukemia reveals multiple off-target side effects. Specifically in testes, TKIs signaling cascades necessary for spermatogenesis are inhibited but the detailed action is not yet fully understood. Therefore, we investigated testicular tissue under TKI exposure in a juvenile rat model. Methods: Growing Wistar rats (age: 4 weeks (w)) were exposed over 10 w to imatinib (IM) or dasatinib (DASA) at different concentrations (low dose [LD], high dose [HD], intermittent high dose [ID]). At prepubertal (age: 6 w), pubertal (8 w), and postpubertal stage (14 w) total testis weight and cellularity (spermatogonia, spermatocytes, spermatids, Ki-67 positive cells) in microscopic tubulus cross section were analyzed under IM exposure. Expression of genes involved in spermatogenesis was analyzed under DASA exposure. Results: In total, 64 and 40 tissue specimen were analyzed for IM and DASA, respectively. Testis weight was not affected by TKI treatment. During IM treatment, compared to controls cell counts were significantly decreased in HD (p = 0.031) whereas LD and ID drug exposure minimized these adverse effects. However, proliferation as assessed by Ki-67 expression was significantly decreased at all IM doses applied. Long-term DASA HD exposure decreased gene expression of SCF, c-kit, PDGF-A/B, and PDGF-R α/β. Conclusion: Long-term TKI exposure seems to influence spermatogenesis dose-dependently, therefore a negative effect on fertility can not be excluded.Annual Meeting of the Kind-Philipp-Foundation for Leukemia Research, Wilsede, Lüneburger Heide, Germany; 06/2015
Conference Paper: Osseous effects caused by Imatinib (IM) in Pediatric Patients with Chronic Myeloid Leukemia (CML).[Show abstract] [Hide abstract]
ABSTRACT: Objective: To investigate alteration of body height, BMI, and bone metabolism in a pediatric CML cohort on upfront IM treatment. Methods: During therapy standard deviation scores (SDS) of body height, body weight, urine and serum were collected in 3-month (mo) intervals. Results: 27 / 111 prepubertal pts (age: < 10 y; 14 ♂ / 13 ♀), 46 pts pubertal pts (age: 10 - 14 y; 25 ♂ / 21 ♀), and 38 postpubertal pts (age: > 15 y; 24 ♂ / 14 ♀) on IM (mean: 16 mo; median 12 mo; range: 0 – 103 mo) showed - compared to mean height SDS at diagnosis - a mean decrease of 0.45 SDS / y and increase in BMI of 0.34 SDS / y in the total cohort during the first 2 y. Height was more affected prepubertally while BMI was more altered pubertally. Urinary bone resorption markers Desoxy-/Pyridinoline continuously decreased during therapy whereas serum formation markers Osteocalcin and Alkaline Phosphatase increased within the first 3 mo followed by a decline until 12 mo and steady state level until 24 mo of therapy. All patients revealed hyperparathyroidism continuously. Conclusion: IM is considered a life-long therapy causing growth retardation as adverse effect in pediatric CML. Thus, regular monitoring of skeletal side effects is warranted.Annual Meeting of the Kind-Philipp-Foundation for Leukemia Research, Wilsede, Lüneburger Heide, Germany; 06/2015
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ABSTRACT: Haemophagocytic lymphohistiocytosis (HLH) in the context of malignancy is mainly considered a challenge of adult haematology. While this association is also observed in children, little is known regarding inciting factors, appropriate treatment and prognosis. We retrospectively analysed 29 paediatric and adolescent patients for presenting features, type of neoplasm or preceding chemotherapy, treatment and outcome. Haemophagocytic lymphohistiocytosis was considered triggered by the malignancy (M-HLH) in 21 patients, most of whom had T- (n = 12) or B-cell neoplasms (n = 7), with Epstein-Barr virus as a co-trigger in five patients. In eight patients, HLH occurred during chemotherapy (Ch-HLH) for malignancy, mainly acute leukaemias (n = 7); an infectious trigger was found in seven. In M- and Ch-HLH, median overall survival was 1·2 and 0·9 years, and the 6 month survival rates were 67% and 63%, respectively. Seven of 11 deceased M-HLH patients exhibited active malignancy and HLH at the time of death, while only two out of five deceased Ch-HLH patients had evidence of active HLH. To overcome HLH, malignancy- and HLH-directed treatments were administered in the M-HLH cohort; however, it was not possible to determine superiority of one approach over the other. For Ch-HLH, treatment ranged from postponement of chemotherapy to the use of etoposide-containing regimens. © 2015 John Wiley & Sons Ltd.British Journal of Haematology 05/2015; 170(4). DOI:10.1111/bjh.13462 · 4.71 Impact Factor
Article: Can prognostic scoring systems for chronic myeloid leukemia as established in adults be applied to pediatric patients?[Show abstract] [Hide abstract]
ABSTRACT: In contrast to adult medicine, specific scoring systems predicting the treatment response for an individual pediatric patient (pt) with chronic myeloid leukemia (CML) have not yet been defined. We evaluated to what extend prognostic scores as described for adults (e.g., Sokal, Hasford, EUTOS score) resulted in comparable risk group categorizations in a pediatric cohort. Parameters for score calculation were extracted from a data set of 90 patients enrolled into trial CML-PAED-II and treated by a standard dose of imatinib. At month 3 and at month 6, treatment response was analyzed based on the transcript ratio BCR-ABL1/ABL1. By the EUTOS, Hasford, and Sokal scores 81, 59, and 62 % of the patients were categorized as low risk, respectively; 19, 14, and 16 % of the patients as high risk, respectively; and by Hasford and Sokal scores 27 and 22 % of the patients, respectively, as intermediate risk. Twenty-seven out of 72 patients analyzable (38 %) exhibited a transcript ratio >10 % at month 3. We show that only the EUTOS score, but not the Sokal and Hasford score, correlates with this early outcome (p = 0.008). Analyzing the EUTOS score separately, we can demonstrate that lowering the cutoff from 87 to 48 points for categorization in low- and high-risk individuals increases the odds ratio from 2.4 (95 % CI 0.6 to 10.4) to 3.6 (95 % CI 1.3 to 10.9). Data are provided on the distribution of risk categories and resulting discrepancies when adult scores are applied on children and adolescents with CML at diagnosis. A larger number of patients and longer follow-up are still needed to develop a prognostic score specifically adapted to the pediatric and adolescent age cohorts.Annals of Hematology 04/2015; 94(8). DOI:10.1007/s00277-015-2367-2 · 2.63 Impact Factor
Article: Bridging to transplant with azacitidine in juvenile myelomonocytic leukemia: A retrospective analysis of the EWOG-MDS study groupBlood 04/2015; 125(14):2311-3. DOI:10.1182/blood-2015-01-619734 · 10.45 Impact Factor
Article: A child with Li–Fraumeni syndrome: Modes to inactivate the second allele of TP53 in three different malignancies[Show abstract] [Hide abstract]
ABSTRACT: Here we report on a child with Li-Fraumeni syndrome with a de novo TP53 mutation c.818G>A, who developed three malignancies at the age of 4 months, 4 and 5 years, respectively. We show that (i) in the choroid plexus carcinoma, the germline mutation was detected in a homozygous state due to copy-neutral LOH/uniparental disomy, (ii) in the secondary AML, a complex karyotype led to loss of the wild-type TP53 allele, (iii) in the Wilms tumor, the somatic mutation c.814G>A led to compound heterozygosity. The findings show that the complete inactivation of TP53 by different mechanisms is an important step towards tumorigenesis. Pediatr Blood Cancer 2015; 9999:1-4. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.Pediatric Blood & Cancer 03/2015; 62(8). DOI:10.1002/pbc.25486 · 2.39 Impact Factor
Article: Chronic Myeloid Leukemia in Children Clinical Findings, Management, and Unanswered Questions[Show abstract] [Hide abstract]
ABSTRACT: Chronic myelogenous leukemia (CML) is a rare disease in children. There is little evidence of biological differences between CML in children and adults, although host factors are different. Children develop distinct morbidities related to the off-target effects of tyrosine kinase inhibitors. The goal of treatment in children should be cure rather than suppression of disease, which can be the treatment goal for many older adults. This article reviews data from the literature on the treatment of CML, discusses the issues that are unique to CML in children, and recommends management that takes these issues into consideration. Copyright © 2015 Elsevier Inc. All rights reserved.Pediatric Clinics of North America 02/2015; 62(1):107-119. DOI:10.1016/j.pcl.2014.09.008 · 2.12 Impact Factor
- British Journal of Haematology 01/2015; 169(5). DOI:10.1111/bjh.13249 · 4.71 Impact Factor
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ABSTRACT: Background: Rothmund-Thomson syndrome (RTS) is associated with an increased risk of osteosarcoma, but information about affected patients is limited. Procedure: Seven patients with osteosarcoma, treated in the Cooperative Osteosarcoma Study Group-trials, had a diagnosis of RTS. Their patient-, tumor- and treatment-related variables and outcome were reviewed retrospectively. Results: Median age at diagnosis of osteosarcoma was 13 years (range 7-16), five were female, two male. Tumor involved proximal tibia (n = 4), distal tibia (n = 1), distal fibula (n = 1) and proximal ulna (n = 1). Three patients had metastatic disease at diagnosis. All patients received surgery and chemotherapy. Four of seven patients required dose modifications and three of them terminated treatment prematurely. Complete resection of the primary tumor was achieved in all individuals. Two of three affected patients failed to achieve surgical clearance of their primary metastases and died. The third patient relapsed with multiple metastases and died. Two of four patients with localized disease were alive in first complete remission, a third patient in second complete remission after recurrence and a fourth patient died of acute leukemia, while still in first complete remission of osteosarcoma. Conclusions: Patients with RTS and osteosarcoma may be cured of their cancer with appropriate multimodal therapy. They should be treated like other osteosarcoma patients but preexisting disorders, needs for special support and development of toxicities have to be considered.Pediatric Hematology and Oncology 12/2014; 32(1). DOI:10.3109/08880018.2014.987939 · 1.10 Impact Factor
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ABSTRACT: Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the presence of the BCR‑ABL1 fusion gene, a constitutively active, oncogenic tyrosine kinase that is responsible for the clinical features of CML. Tyrosine kinase inhibitors, such as imatinib, have markedly altered the treatment of CML. However, tyrosine kinase inhibitors are associated with side effects on bone metabolism, in adult and pediatric patients. Vitamin D3 is involved in the complex cycle of bone remodeling, therefore the present study aimed to investigate the influence of imatinib on vitamin D3 metabolism in the HaCaT human keratinocyte cell line, using commercially available enzyme assays. Imatinib was shown to significantly reduce the production of calcidiol and calcitriol. Based on interaction studies of imatinib with the cytochrome P450 (CYP450) inhibitors VID400 and ketoconazole, it is proposed that imatinib may interfere with the vitamin D3 cascade due to its metabolism by CYP27B1, which is involved in vitamin D3 metabolism.Molecular Medicine Reports 12/2014; 11(4). DOI:10.3892/mmr.2014.3074 · 1.55 Impact Factor
Conference Paper: Impairment of Longitudinal Growth by Tyrosine Kinase Inhibitor (TKI) Treatment - Data from a Large Pediatric Cohort with Chronic Myeloid Leukemia (CML).[Show abstract] [Hide abstract]
ABSTRACT: Objectives: A decade after being licensed for treatment of CML in minors, the TKI imatinib (IMA) is well known for it's inhibitory "off-target" effects on activity and proliferative capacity of osteoclasts and osteoblasts resulting in impaired bone remodeling (Vandyke K et al 2010 Blood 115:766; Tauer JT et al Blood 2011:118). This causes longitudinal growth retardation in not outgrown individuals (Millot F et al 2009 Blood 114:863; Shima H et al 2011 Pediatrics 159:676; Bansal D et al 2012 Ped Blood Cancer 59:481) which can be aggravated by a disrupted growth hormone:IGF-I axis as a possible additional off-target effect exerted by TKI treatment (Ulmer A et al 2013 Klin Padiatr 225:120; Bansal D et al 2012 Ped Blood Cancer 59:481). Starting a pediatric trial in the year 2006 which recruits approx. 15 pediatric patients (pts) with CML annually, we investigated to what extend growth is impaired depending on sex, age, and pubertal stage at start of IMA treatment in a pediatric cohort. Methods: 102 pts (54 male / 48 female; median age 12 years, range: 1-18 years) at diagnosis of CML receiving IMA as upfront treatment were enrolled retrospectively in this analysis from centers in Germany and participating countries during 02/2006 to 06/2014. Height standard deviation scores (SDS) were derived from WHO-AnthroPlus, version 1.04 software, a global growth-monitoring tool providing normal range values for the age cohorts from birth till 19 years. 81 out of 102 pts fulfilled the criteria for continuous assessment of growth scheduled at three months intervals during IMA exposure. 21 pts were analyzed at intervals ≠ 3 month. Pts excluded comprised individuals shifted to a 2nd generation TKI, or cumulative interruptions of drug intake exceeding 4 weeks, or pts undergoing stem cell transplantation. Results: The mean and median duration of IMA exposure was 12 months and 9 months, respectively (range: 0–98 month). 27/102 pts (13 male, 14 female) were prepubertal (age: <10 years) at initiation of IMA treatment while 46/102 pts were pubertal (age: 10-14 years; 23 male, 23 female), and 29/102 pts were in postpubertal stage (age: >14 years; 18 male, 11 female). In comparison to mean SDS at diagnosis a mean decrease in height of 0.48 SDS per year was observed in the total cohort during the first three years of treatment, being more pronounced in prepubertal pts. In pts diagnosed shortly before or at puberty a mean reduction of 0.75 SDS per year during the first three years were observed. Older teenagers revealed no change in body height z-score during TKI treatment compared to height z-score at diagnosis. Discussion: Growth retardation is a significant adverse effect of IMA in children with CML affecting predominantly prepubertal children. Possible medical interventions still need to be investigated. Acknowledgement: Supported by grant DFG SU122-3/1 to MS.American Socienty of Hematology (ASH), San Francisco; 12/2014
Article: Decisions Taken in Children and Adolescents with Chronic Myeloid Leukemia (CML) at Failure of Imatinib TreatmentBlood 12/2014; 124(21). · 10.45 Impact Factor
Article: Sustained Complete Molecular Remission after Imatinib Discontinuation in Children with Chronic Myeloid Leukemia[Show abstract] [Hide abstract]
ABSTRACT: Approximately 40% of adults with chronic myeloid leukemia (CML) in prolonged complete molecular response (CMR) remain in CMR after imatinib discontinuation. Corresponding information in children is lacking. Two children with CML in CMR for 48 and 19 months after imatinib discontinuation showed low-level fluctuating disease at RNA transcript and genomic DNA levels. Both patients were low risk according to adult criteria. Since adults with molecular relapse responded to re-introduction of imatinib, we postulated that treatment discontinuation in low risk children might be justified within clinical trials with close monitoring. This may help to minimize exposure to imatinib and its potential side effects. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.Pediatric Blood & Cancer 11/2014; 61(11). DOI:10.1002/pbc.25090 · 2.39 Impact Factor
- Pediatric Blood & Cancer 07/2014; 61(7). DOI:10.1002/pbc.24933 · 2.39 Impact Factor
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Carl Gustav Carus-InstitutPforzheim, Baden-Württemberg, Germany
Technische Universität Dresden
Dresden, Saxony, Germany
- Klinik und Poliklinik für Kinder- und Jugendmedizin
University of Iowa Children's HospitalIowa City, Iowa, United States
Universität UlmUlm, Baden-Württemberg, Germany
Universitätsklinikum Schleswig - Holstein
Kiel, Schleswig-Holstein, Germany
- Klinik für Allgemeine Pädiatrie (Kiel)
Christian-Albrechts-Universität zu Kiel
Kiel, Schleswig-Holstein, Germany
- • UKSH II. Medizinische Klinik und Poliklinik
- • Abteilung für Allgemeine Pädagogik
University of PaviaTicinum, Lombardy, Italy


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Leading Catholic Church law judge and bishops support Catholics faithful to spouses after divorce
Catholic PRWire
Cardinal Raymond Burke, an American who leads the Catholic Church's highest internal tribunal, said that Cardinal Walter Kasper caused unnecessary confusion for Catholics in statements the latter made about marriage.
ROCKY RIVER, OH (July 12, 2014) - BY BAI MACFARLANE
Cardinal Raymond Burke, the Prefect of the Supreme Tribunal of the Apostolic Signatura (the highest canon law court in the Catholic Church) corrects confusion spread by those who say the Church is going to change teaching about divorced and remarried receiving Holy Communion. On June 29, EWTN aired an interview of Cardinal Burke by Thomas McKenna, president of Catholic Action for Faith and Family. McKenna asked Cardinal Burke about proposals that the upcoming extraordinary synod of bishops will change the Church's teaching on remarriage after divorce. Cardinal Burke explained that this could never happen and that Cardinal Kasper caused confusion when his talk to bishops in April was publicized.
The Church can't bend to the culture when the culture errors, said Cardinal Burke:
"Some people say 'Well the culture is predominantly divorcist and therefore the Church in her practice has to adapt herself to the situation of the culture.' That is not the nature of the Church. When the Church confronts a culture that is in some way weak or defective, or failing, as our culture is, Her mission is to call the culture to conversion and to teach ever more strongly the truth about marriage and to help, of course, individuals to live according to that truth. I think for instance of example in France and also in the United States, of associations of those who are divorced who meet regularly to encourage one another to remain faithful to their marriage (to their first marriage) because they believe very sincerely in the Lord's teaching that marriage was in fact, or is in fact, a way to salvation, and so these are the kinds of things that we ought to be encouraging ..." See YouTube. https://www.youtube.com/watch?v=6jfiEPvRyBA
In a divorcist culture, divorce persons believe they are single again, and if feel like it, they should start dating again to find a "new spouse." In some particular situations, marriages are not valid. The Catholic Church with a decree of invalidity recognizes these situations officially. But all marriages wherein someone filed for divorce are not invalid.
Recently, on June 24, the Vatican released the survey results from the consultation of bishops that was part of the preparation for the upcoming synod about the Family. In the Vatican's document "Instrumentum Laboris" they emphasized the interest in avoiding petitioning for decrees of invalidity with improper discernment, and the witness made by separated persons who remain faithful to their marriage vows:
"Various responses and observations want to see more attention given to separated and divorced persons who have not remarried but have remained faithful to their nuptial vows. Oftentimes, these people seem to have the added suffering of not being given proper care by the Church and thus overlooked. Such persons also have difficulties and a need for pastoral attention. Moreover, the responses emphasize the importance of a pastor's due care in seeing whether a marriage annulment is possible so as not to introduce cases without proper discernment. In this process, many responses ask for a concerted effort towards reconciliation to see if the separated parties can be reunited. Some responses refer to the great Christian witness made by separated persons who, courageously accepting their situation of suffering and solitude, remain faithful to their marriage vows."
Cardinal Burke, without naming organizations, spoke of such persons in both France and the U.S. In France, "Communion Notre Dame de l'Alliance" is a private association of the faithful recognized by the Conference of Bishops of France and Belgium. In Vermont, "Solitude Myriam" describes itself on their website as a group of persons who "continue their vocation of marriage. They learn to receive grace for their family in faithfulness to their sacramental marriage vows, even as they live 'in solitude', without their spouse."
In the U.S., another group organized by Mary's Advocates, a non-profit organization upholding marriage, support each other and use a book translated from Italian to English as their program manual, "The Gift of Self" by Maria PiaCampanella. The initiative of the United States Conference of Catholic Bishops that is supporting marriage featured as it's June book review this book: "The Gift Of Self: A Spiritual Companion For Separated And Divorced Faithful To The Sacrament Of Marriage."
The USCCB's review stated, "The greatest strength of Campanella's book is her articulation of the vocation of the separated person to live out his or her marriage vows as a particular witness of God's eternal love for fallen humanity, and the practical path she offers to the realization of this call." See:http://www.foryourmarriage.org/the-gift-of-self-a-spiritual-companion-for-separated-and-divorced-faithful-to-the-sacrament-of-marriage/
As Cardinal Burke said, when the Church faces a culture that is week or failing, the Church's mission is to call the culture to conversion. "Communion Notre Dame de l'Alliance" in France, "Solitude Myriam" in Vermont, and those following the path in the book "The Gift of Self," by their own private example are calling the culture to conversion.
Mary's Advocates
http://www.speroforum.com/a/QFHDZDQVTH24/75015-Leading-Catholic-Church-law-judge-and-bishops-support-Catholics-faithful-to-sp OH, 44116 US
Bai Macfarlane - ,
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Politics Among Nations / Edition 7by Hans Morgenthau, Kenneth Thompson, David Clinton, Kenneth W. Thompson
Hans Morgenthau's classic text established realism as the fundamental way of thinking about international relations. Although it has had its critics, the fact that it continues to be the most long lived text for courses in international relations attests to its enduring value. Someone has said the study of international relations has for half a century been nothing so… See more details below
Hans Morgenthau's classic text established realism as the fundamental way of thinking about international relations. Although it has had its critics, the fact that it continues to be the most long lived text for courses in international relations attests to its enduring value. Someone has said the study of international relations has for half a century been nothing so much as a dialogue between Morgenthau, those who embrace his approach, and those who turn elsewhere for enlightenment. After
50 years, the dialogue between Morgenthau and scholars from around the world continues more or less as in the past something with more intensity even in an "age of terror."
The new edition preserves intact Morgenthau's original work while adding a 40 page introduction by the editors who explore its relevance for a new era. What follows the introduction are the perspectives of a dozen statesmen,
scholars, and observers each offering insights on Morgenthau's concepts and ideas as they relate to current crises on every continent. They bring up to date the dialogue that began in 1948.
Product Details
- 9780072895391
- Publisher:
- McGraw-Hill Professional Publishing
- Publication date:
- 04/19/2005
- Edition description:
- New Edition
- Pages:
- 752
- Sales rank:
- 330,411
- Product dimensions:
- 7.50(w) x 9.10(h) x 1.10(d)
Table of ContentsFOREWARD: On the Continuing Relevance of Politics Among Nations
PART ONE: Theory and Practice of International Politics
1A Realist Theory of International Politics
2The Science of International Politics
PART TWO: International Politics as a Struggle for Power
3Political Power
4The Struggle for Power: Policy of the Status Quo
5The Struggle for Power: Imperialism
6The Struggle for Power: Policy of Prestige
7The Ideological Element in International Policies
PART THREE: National Power
8The Essence of National Power
9Elements of National Power
10Evaluation of National Power
PART FOUR: Limitations of National Power: The Balance of Power
11The Balance of Power
12Different Methods of the Balance of Power
13The Structure of the Balance of Power
14Evaluation of the Balance of Power
PART FIVE: Limitations of National Power: International Morality and World Public
15Morality, Mores, and Law as Restraints on Power
16International Morality
17World Public Opinion
PART SIX: Limitations of National Power: International Law
18The Main Problems of International Law
PART SEVEN: International Politics in the Contemporary World
20The New Moral Force of Nationalistic Universalism
21The New Balance of Power
22Total War
PART EIGHT: The Problem of Peace: Peace Through Limitation
25Judicial Settlement
26Peaceful Change
27International Government
28International Government: The United Nations
PART NINE: The Problem of Peace: Peace Through Transformation
29The World State
30The World Community
PART TEN: The Problem of Peace: Peace Through Accommodation
32The Future of Diplomacy
Appendix A: Updating Realism for the 21st Century
* Admiral William J. Crowe, Jr.: "An Iraq Retrospect."
* General Brent Scowcroft: "New Departures in the Philosophies of International Politics."
* Ambassador David Newsom: "Did the U.S. Win the Cold War?"
* John J. Mearsheimer, U of Chicago: "The False Promise of International Institutions."
* J. Samuel Barkin, U of Florida: "Realist Constructivism."
* Richard Little, "The English School vs. American Realism: a meeting of the minds or divided by a common language?"
* Ashley Tellis, "Political Realism: The Long March to Scientific Theory."
Appendix B: Charter of the United Nations
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September 25, 2015 Cross CountryMen's Cross Country Takes Sixth At Battle of Beantown, Women Place Seventh Competing in its second event of 2015, Harvard men's cross country placed sixth while the women finished seventh at the Coast to Coast Battle of Beantown at Franklin Park. [read more]
September 24, 2015 Cross CountryCross Country Readies for Coast to Coast Battle of Beantown The Harvard men's and women's cross country teams continue the 2015 season at the Coast to Coast Battle of Beantown, hosted by Boston College at Franklin Park. The women's race will begin first at 3 p.m. followed closely by the men's run at 3:30 p.m. [read more]
September 11, 2015 Cross CountryWomen's Cross Country Wins HYP, Purnell Claims First on Men's Side Competing at the annual Harvard-Princeton-Yale (HYP) meet, Harvard women's cross country finished in first place with 36 points. The men's team was led by individual champion senior Thomas Purnell, but the Crimson finished in a tie for second with Yale. [read more]
September 10, 2015Around The Yard: Tyler Spear I moved back to campus on Monday the 24th, about a week before the rest of the student body, so that cross country practices could begin before we got caught up in the rush of the 2015 academic year. My roommate Ben, and I carried heavy bags of clothes, books, school supplies, and snack food into Kirkland House, and settled into our room. Everything was so quiet; halls and rooms were empty, most dining halls were dark, and no one sat on benches in the courtyard, or played frisbee on the grass. I quickly began to feel like someone had decided to hide me away from the rest of campus, to cut me out of the goings-on around the College. [read more]
September 10, 2015 Cross CountryCross Country Opens Season with Yale, Princeton The Harvard men's and women's cross country teams open the 2015 season at home with the Harvard-Yale-Princeton meet at Franklin Park. The women's race will begin at 2 p.m. and the men's sprint an hour later at 3 p.m. [read more]
August 31, 2015 FootballCoaches as Educators - Coaching Harvard Athletes Aug. 31, 2015
August 6, 2015 Track & FieldTrack and Field, Cross Country Announce Class of 2019 The Harvard track and field team has announced the addition of 28 newcomers, 16 men and 12 women, to join the roster as the Class of 2019. Below is a breakdown of each of the incoming student-athletes. [read more]
August 4, 2015 FootballHarvard Athletics Facilities Update - Summer 2015
Cross Country
Cross Country
Cross Country
Cross Country
Track & Field
/sports/xc/2015-16/photos/0004/IMG_7483_NEW_Rotator.jpg?max_width=1000&max_height=525 /sports/xc/2015-16/CCC_Battle_fo_Beantown_NEW_Rotator.jpg?max_width=1000&max_height=525 /sports/xc/2015-16/photos/0001/IMG_1867_NEW_Rotator.jpg?max_width=1000&max_height=525 /Around_The_Yard/2015-16/Photos/Tyler_Spear_Top_Story_NEW_Rotator.jpg?max_width=1000&max_height=525 /sports/xc/2015-16/photos/0001/IMG_1867_NEW_Rotator.jpg?max_width=1000&max_height=525 /sports/wice/2015-16/photos/Stone_CAE_Web.jpg?max_width=1000&max_height=525 /sports/track/2013-14/photos/Harvard_Track_and_Field?max_width=1000&max_height=525 /sports/fball/2015-16/FBL_1415_Aerial_013.jpg?max_width=1000&max_height=525


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Abu Dhabi 2012: 'The Last Stand' Foley Supervisor Shoots Down Hollywood Sound Expert Claim
Gary Hacker denies that work on the Arnold Schwarzenegger film was rushed, as Michael Broomberg previously suggested.
ABU DHABI – Gary Hacker, supervising Foley artist on the new Arnold Schwarzenegger movie The Last Stand, has slapped down fellow sound worker Michael Broomberg for publicly suggesting that sound post-production on the Lionsgate film was hurried.
Broomberg, a Hollywood sound artist whose studio work includes War of the Worlds and Watchmen, told an Abu Dhabi Film Festival panel audience that shrinking sound budgets for independent films was "madness." During his Masterclass, he said that independent producers never earmark enough money for Foley work. Broomberg added that he had just eight days to do Foley work on The Last Stand, "a big action film with lots of guns and explosions."
PHOTOS: Fall Movie Preview 2012: Major New Releases From Spielberg, Jackson, Tarantino, the Wachowskis, Burton and More
However, one source close to the production said that the Foley schedule for The Last Stand was more extensive than Broomberg realized. Foley work lasted much longer than eight days.
Countered Hacker: "Broomberg was brought in to provide four days of Foley services as a temporary replacement. As such, he is unaware of the totality of the scope of the work performed for this project."
For his part, Broomberg has completely retracted what he said publicly in Abu Dhabi. Broomberg said that he regretted making a series of "grossly inaccurate representations" about The Last Stand during his Masterclass.
VIDEO: 'The Last Stand' Trailer Marks Arnold Schwarzenegger's Comeback
"I particularly regret that I misrepresented myself and the film based on assumptions I now know to be faulty regarding the scope of work performed prior to my arrival and following my departure from the project," Broomberg said in his mea culpa.
Hacker added: "I am proud of the work we performed on The Last Stand ... I am completely confident in our ability to provide top-quality Foley services to all our clients."
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Sullivan & Son: Season 2, Episode 10
Reunited (22 Aug. 2013)
TV Episode | | Comedy
Ratings: 7.5/10 from 19 users
Reviews: write review
Carol and Owen practice to perform at the bar's music talent competition, but Carol meets Daryl, a newcomer to the bar, and only wants to perform with him. The bar regulars try to get OK Cha drunk.
Director:Phill Lewis
Writers:Rob Long (creator), Steve Byrne (creator), 1 more credit »


text:
Former Penn State president Graham Spanier is asking a federal judge to halt his prosecution in Dauphin County for an alleged criminal cover-up of complaints about Jerry Sandusky.
Spanier's lawyers filed a complaint in federal court in Harrisburg Monday that says his case was ``undertaken in bad faith'' and that it violates his constitutional right to due process of law.
A message left for the defendant, Attorney General Kathleen Kane, wasn't immediately returned.
Spanier is awaiting trial in Dauphin County along with former Penn State vice president Gary Schultz and former athletic director Tim Curley.
In that case, the defendants are waiting for a decision by the trial judge regarding claims that their right to legal representation was violated by the actions of former Penn State general counsel Cynthia Baldwin.
Graham Spanier, former Penn State president, asks federal court to halt criminal case
Former Penn State president Graham Spanier is asking a federal judge to halt his prosecution in Dauphin County for an alleged criminal cover-up of complaints about Jerry Sandusky.
Copyright 2014 WFMZ. The Associated Press contributed to this report. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
More Pennsylvania Headlines
- Pennsylvania attorney general charged with 2nd perjury count
- Pennsylvania emergency officials prepare for Joaquin's impact
- NWS confirms EF-1 tornado touched down in Lancaster County
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- State Supreme Court upholds cop killer's death sentence
- Some Pennsylvania schools hurting as budget battle continues
- Pa. Turnpike to test cashless toll system next year
- Festival of Families in Philadelphia
- Churches from Lehigh Valley head to Philadelphia for pope's historic visit
- Pope Francis inspires thousands in attendance at Independence Hall
- Crowds pack the streets of Philadelphia to catch a glimpse of the pope
- WFMZ's coverage of Pope Francis' visit to Philadelphia
- Philadelphia quiet before papal visit
- Berks K9 unit, others dispatched to Philly for papal visit
- Man gets life term in fatal shooting at hospital
- Suspended license puts AG's re-election bid in jeopardy
- Seminary puts pope-inspired beer on tap for Francis' stay
- Downtown Philadelphia deserted ahead of Pope Francis' visit
- State House passes short-term spending plan
- Kutztown EMS crew chosen to work pope's Mass in Philadelphia
- Lawmakers react to Pope Francis' address to Congress
- Kutztown University band chosen to appear in Thanksgiving Day parade
- Buenos Aires to Philly: Family drives 13,000 miles to see pope
- Pope 'Phrancis' dolls, beer and cheese for sale in Philly
Pennsylvania Sports
- Phantoms win final preseason game
- Jesse Biddle to have Tommy John surgery
- Cousins burns Eagles late as Washington tops Philadelphia
- Kutztown hammers Millersville to go to 2-0 in league play
- Phantoms fall to Hartford in tuneup
- Fordham runs past Lafayette in Patriot League opener
- Hall of Fame coach Bob Hurley visits Berks County
- Moravian, Muhlenberg win at home; Albright goes to 4-0
- Yale too much for Mountain Hawks
- Royals to open training camp Saturday


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Known for the endless pizza, pasta, salad, soup and dessert buffet in Huntsville, AL, the CiCi's Pizza Huntsville is a neighborhood favorite for flavor adventure. More 100% real cheese, more meat toppings and garlic butter crust add up to a better than ever meal...
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Cici's first opened in Plano, Texas, in 1985 and has since spread to locations throughout the Southeast and Midwest. Known for its one low, all-you-can eat price, the...
Francisco always makes good pizzas
Lee Hadden had stopped in for lunch and then pitched in because neither manager Chris nor Richard were there, leaving the store short-handed to handle customer volume. Lee, as he used to do when he was the GM for the store, came out from behind the bar to bus tables and speak with the customers, something I have never seen Chris nor Richard ever do. Lee's actions made for a better dining...
For an endless variety of pizza, desserts, and pasta that the entire family will love, visit the CiCi's Pizza HUNTSVILLEand experience the flavor adventure that you crave.
Visit a CiCi's Pizzza restaurant near you for fresh pizza, pasta, salads and desserts, or pick up your favorites and go home a hero. CiCi's Pizza Buffet makes it easy.
Save Money: Meals are free for children 3-years-old and under.
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Blog — E3G response to BoE: Breaking the Tragedy of the Horizon – climate change and financial stability
In response to Mark Carney's speech to Lloyds of London, E3G welcomes a key moment in the orderly transition to 2°C
In response to Mark Carney's speech to Lloyds of London, E3G welcomes a key moment in the orderly transition to 2°C
The oil industry is busy setting a big trap for environmentalists. Tom Burke unpicks the carbon pricing problem.
Paris isn't a done deal. European decisions this week can strengthen momentum for a long-term goal and ambition mechanism to deliver 2°C
Join the E3G Climate Finance team's project to influence and deliver change accross Europe
Exploring the financing and investment challenges for implementation of China's goals for decarbonising its economy.
Maximising the impact of COP21 and international climate diplomacy.
E3Gers comment on what's been happening across the globe.
Cities are getting more vocal, energised and organized in the climate and energy debate in Europe and worldwide.
Ensuring a just and fair transition for workers and regions in high carbon industries that risk losing out.
Achieving a coherent, secure and sustainable energy system for Europe.
Campaign on using carbon tax to make fuel poor homes energy efficient.
E3G celebrates 10 years of advancing security and prosperity for an interdependent world
Accelerating the development of a North Seas Offshore Grid in line with European energy and climate goals.
Addressing the politics and policy of low-carbon technology deployment.
From instruments to drive cost-effective decarbonisation to implications for EU diplomacy.
Implications on politics, national climate and energy policies, and completion of the internal energy market


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DEFINITION of 'Market Maven'
A slang term used to describe an investor who is "in-the-know." The term "market maven" usually refers to an individual who is a market participant with a great deal of knowledge and connections, thus having a trusted opinion on market events or speculation. Historical success in the market is typically the driving force behind those who are considered mavens and those who are not.
BREAKING DOWN 'Market Maven'
In general, the term is used to describe consumers who have up-to-date information about products, places to shop and different markets. This definition makes sense when talking in the context of the stock market, as the nature of the market itself is highly speculative and based upon opinions in most cases. The media looks to market mavens for opinions and strategies for retail investors and onlookers to follow.
MarketA medium allowing buyers and sellers of a specific good or service ...
Warren BuffettKnown as "the Oracle of Omaha", Buffett is Chairman of Berkshire ...
SpeculatorA person who trades derivatives, commodities, bonds, equities ...
PoopA slang term often used to describe inside information or people ...
Whisper Number1. Traditionally, the unofficial and unpublished earnings per ...
Equity MarketThe market in which shares are issued and traded, either through ...
Investing Basics
The Intelligent Investor: Benjamin GrahamLearn about the man who mentored Warren Buffett, who eventually became the investing "Oracle of Omaha".
Active Trading
Warren Buffett: How He Does ItWe look at the Sage of Omaha's methodology for evaluating value stocks.
Investing Basics
Think Like Warren BuffettThey don't call him "The Oracle" for nothing. Learn how Buffett comes up with his winning picks.
Consumer Confidence: A Killer StatisticThe consumer confidence is key to any market economy, so investors need to learn the measures and how to analyze them.
Options & Futures
Financial Wisdom From Three Wise MenLearn nine simple rules to success from the talented Buffett, Gartman and Pearson.
How to Win More by Losing Less in Today's MarketsThe further you fall, the harder it is to climb back up. It's a universal truth that is painfully apparent in the investing world.
Fundamental Analysis
Value Investing Strategies in a Volatile MarketVolatile markets are a scary time for uneducated investors, but value investors use volatile periods as an opportunity to buy stocks at a discount.
Mutual Funds & ETFs
Using Short ETFs to Battle a Down MarketInstead of selling your stocks to get gains, consider a short selling strategy, specifically one that uses short ETFs that help manage the risk.
Mutual Funds & ETFs
How to Lower Investment Account Fees in RetirementRetired investors need all the money they have, which is why they should keep an eye on investment fees, as high fees can lower returns.
Investing Basics
Calculating Capital Gains YieldCapital gains yield refers to a security's appreciation or depreciation during the time it's held.
Where do penny stocks trade?Generally, penny stocks are traded through the use of the Over the Counter Bulletin Board (OTCBB) and through pink sheets. ... Read Full Answer >>
Where can I buy penny stocks?Some penny stocks, those using the definition of trading for less than $5 per share, are traded on regular exchanges such ... Read Full Answer >>
How does the stock market react to changes in the Federal Funds Rate?The stock market reacts to changes in the federal funds rate in various ways depending on where it is in the business cycle. ... Read Full Answer >>
What are the requirements for being a Public Limited Company?The requirements for an entity to be considered a public limited company (PLC) include registration requirements, establishing ... Read Full Answer >>
How do I place an order to buy or sell shares?It is easy to get started buying and selling stocks, especially with the advancements in online trading since the turn of ... Read Full Answer >>
Is there a difference between financial spread betting and arbitrage?Financial spread betting is a type of speculation that involves a highly leveraged derivative product, whereas arbitrage ... Read Full Answer >>


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Fad Treasures Double Skull & Crossbones Necklace Grindstore
(approx. $7.52 or €6.81)
- In Stock
- Usually Ships in 1-2 Days
- UK & Worldwide Delivery
- Product Type: Necklace
- Product Code: 71886
One crystal embellished skull dangles from another on this spooky necklace with a twist. Perfect for fans of gothic accessories this awesome necklace will add a bit of bling to even the darkest of outfits.


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In partnership with GPIC and Penn State, PennDesign hosted a symposium exploring the intersection of architecture, style and building energy efficiency. Architecture and Energy is a collaboration between the University of Pennsylvania School of Design and Pennsylvania State University and sponsored by the Greater Philadelphia Innovation Cluster (GPIC) for Energy-Efficient Buildings, a U.S. DOE Energy Innovation Hub led by Pennsylvania State University. Here Assistant Professor of Architecture Franca Trubiano presents on "Designing High Performance - The Ethical Representation
of Net Zero."
For details, visit architectureandenergy.com.
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Enzo Angiolini, delivers attainable luxury to the confident and cultured consumer who appreciates the product's attention to detail, rich materials and fine craftsmanship.
Here are some of the Enzo Angiolini Shoes that we carry at Heels.com:
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Tuesday, July 24, 2012
Author: Sunita Khatri
A company's workforce has many facets, varied abilities and diverse needs. HR must ensure their technical systems meet both their staff's and their employer's practical requirements to achieve objectives. In this article, Humair Ghauri of Oracle looks at the challenges faced by HR departments implementing vital developments to working processes and measuring their effectiveness. Read the full article here.
By Tara Swords National Instruments (NI) is a complicated...Read More
Originally posted on Profit Capgemini helps Oracle customers...Read More
By David Baum - Originally posted on Profit Peter Bjork grew...Read More
Part 1 introduced the challenges and opportunities customers...Read More
By Mike Bollinger & Alex Anvari HR and finance executives...Read More
By Aaron Lazenby In the age of digital disruption, there's...Read More
By Mark Bennett - Originally featured in Talent Management...Read More
By Mark Bennett In Part 1, we reviewed the challenges that...Read More
By Anu Kurian - Originally posted on people matters Aaron...Read More


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UK Overnight
Patchy rain in the northwest. Dry and bright elsewhere.
Northwest Scotland and Northern Ireland will remain cloudy with occasional outbreaks of rain and the odd shower may affect the far southeast of England. The rest of the UK will stay dry with clear spells and some fog patches.


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- Fabio Viviani born (1978)
We Need This Oreo Separating Machine in Our Lives
Today on The Daily Meal
Recipe of the day
Remember that Oreo Super Bowl ad where people got into a whisper fight arguing about the best part of an Oreo? Well, here's a machine to bring the two sides together.
The cookie company commissioned physicist (and cookie-part lover) David Neevel to build a machine that separates the cream from the cookie. The final machine he builds is incredibly cool (although it's prefaced by a "DO NOT ATTEMPT" caption), where the machine slices the cookie in half, sets the cookies cream side up, and scrapes all the cream off.
One qualm we do have with this design: the scraped off cream just ends up in clumps, almost like trash. We know Neevel likes the cookie part better, but come on man. We could be best friends. Just find a better way to present the filling at the end and we're good.
Watch the machine in progress below, with the full process as seen from above starting at 3:30.
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9 Epically Awesome Photos Every Lafayette Instagrammer Takes
Lafayette loves it some Instagram.
Lafayette loves it some Instagram.
According to NPD Group, research shows that there are at least 500 celebrity fragrances released each year. That's quite an obscene number since… well, are there even 500 celebrities worthy of fragrances out there? Of course with each new fragrance comes the expected Best and Worst lists, and sadly, Katy Perry's fragrance "Purr" made the latter.
Following the release of his the Nicki Minaj-assisted banger 'I Luv Dem Strippers,' another 2 Chainz track leaks online called 'Yuck' featuring Lil Wayne. As the title suggests, the song is nasty… lyrically.
After a recent gymnastics competition at the 2012 London Olympics, the United States gymnast McKayla Maroney was NOT impressed with the Silver Medal her team won. Since then, her disappointment has gone viral, and now someone on Tumblr is having fun placing the gymnast in various situations and places.
The Jackson Family feud has become a PR nightmare for Michael Jackson's siblings and a heartbreaking story for their fans. Amid television reports of an alleged fight at Katherine's house and other tawdry gossip, no one seems to know what the heck is going on with the R&B family.
Sherman Hemsley, a television fixture of the '70s and '80s, has died at his home in El Paso, Texas at age 74. His passing is being attributed to "natural causes."
The last time I checked, relationships aren't that hard....either you love them or you don't! After dating each other for almost a year and a half, it looks like Justin Bieber and Selena Gomez are finally on the rocks. If you didn't know, this means guys are laughing at Justin for leaving her and 13-year-old girls are screaming that he is single once again.
The official start of summer is only days away, and while some are excited for the sunniest of seasons, others are all to aware of the constant dangers presented by the summer sun...
Tears are hitting my keyboard as I reluctantly type the bad news. Iconic jean company Marithe Francois Girbaud has filed for chapter 11 bankruptcy, which means they are re-organizing their debt and may actually stay in business. Girbaud jeans literally defined "cool" in the 80's and 90's and were pioneers of the denim washes, particularly stone washing. The brand also gained popularity heading into the new millennium as a result of being heavily referenced by rappers like Notorious B.I.G. and The Hot Boys.
Lafayette is often recognized for it's delicious food and amazing culture. Recently, we were dubbed the 'Tastiest Town' according to Southern Living. We also just celebrated Festival International de Louisiane which was crowned as the best for world music. Tell somebody to make some room on Lafayette's trophy shelf for another top honor as our very own Sneaker Politics was recently ranked by Complex Magazine as one of the 10 Best Sneaker Shops In The South.


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The hotel staff was friendly and helpful. They gave good directions and printed maps. Very clean room and large shower. The airport shuttle was convenient and easy to use.
No was cloth.
I loved the convinceof your wifi! It worked with no hassles!! Thank you!! The front staff were friendly and helpful.Quiet hotel
bed side wall plugs would be nice to plug in devices.The handle bar in the elevator is poor and pinced my hand Bigger TVThe flooring in the shower hurts your feet.
The front desk employees were very helpful, very clean and great value for the price.
The breakfast was fantastic, the room clean, bed comfortable.
It was very difficult to adjust the water temperature of the shower.
Could not get the wi-fi to work in the room in the morning. As there was a charge of €5 per device for a 24hr period this was disappointing. There was no trouble connecting to the wi-fi in the breakfast area though.
The hosts are wonderful people. The bed was very comfortable and the room spotless. The location being a 5 minute drive from the airport makes it very convenient. Thank you.
Great location. Easy access to airport. Great staff. Good food. Nice common area for meeting with fellow travellers.
Definitely the best place we stayed on an extended Europe Trip! The friendliest people who helped set us up with everything we needed. The breakfast was an incredible atmosphere. Wish we could have spent more time there!
Staff were busy, but pleasant on arrival & departure.
Chef not on duty Sunday evening, menu was all beef. Able to get chicken which was dry! Room rather small, plus having to carry bags up stairs without assistance. Breakfast not served until 9am, problem when having to be at the airport for 9-20am.
The personal service the owner Simon took to make us feel welcome.What ever we needed he took care of. We just loved this. He called for transportation, provided umbrellas to borrow and also helped get our morning breakfast. Such service!!
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Join us here in the pretty harbour town of Kirkcudbright, known nationally as "The Artists Town".
The story of its artists' colony is full of examples of artists arriving on a summer painting visit and staying on for the rest of their lives.
The reasons why Kirkcudbright attracted so many painters and became an artists' colony are not difficult to discern. It was, and remains, perhaps the most attractive small town in Scotland with impressive architecture. There is the High Street with its ancient Tollbooth and the 18th century town houses enlivened by their variously and sometimes eccentrically painted frontages, the myriad colours giving the street an exotic, almost continental, atmosphere. Between the houses are cobbled, crooked wynds, many of which contain artist's and craftsmen's studios. McLellan's Castle an imposing sixteenth century ruin in the middle of the town, dominates the skyline. When E.A.Taylor asked Hornel why he thought Kirkcudbright was so popular with artists he said, "Well, it's a fine old town and not too big, but big enough to keep you from vegetating.
Friday 13th and Saturday 14th November 2015
£229.00 per person, includes Dinner Bed and Breakfast, welcome drink & canapés, coffee breaks, soup and sandwich lunches.
No single room supplement
This art appreciation weekend is designed to increase your enjoyment of art in a relaxed and informal setting. There is time during the illustrated talks for questions and discussion. Your tutor Jeremy Carlisle BA (Hons) MA is a practising artist and art historian.
This weekend Jeremy will be concentrating on the following artists:
Titian invented painting – discuss. Titian invented modern painting – discuss further! Some think Titian was the greatest painter of the High Renaissance, if not of the entire history of painting. He had a huge influence on all subsequent schools of painting, particularly as a colourist.
Titian 'Bacchus and Ariadne' 1522-1523
Chardin is the undemonstrative genius of 18C French painting. His often overlooked contemplative paintings are beautiful, profound and timeless. He is probably best known for his still-lives but he also painted people, particularly women and children, with a rare intimacy, warmth and tenderness.
Chardin 'Glass of Water and Coffee Pot' 1760
In contrast to Chardin, Delacroix's work is expressive and at times almost expressionist in its calligraphy. His journals are one of the most absorbing accounts of a painter's life and offer rich insights into the mind of this highly intelligent painter. His little known and rarely seen direct studies from nature were an inspiration to the Impressionists. They are a revelation.
Delacroix 'Algerian Women' 1834
We didn't have time in our survey of the Glasgow Boys and Glasgow girls at the Selkirk in 2013 to do justice to the watercolours of these two superb masters of this craft.
Both artists travelled to Spain and North Africa and returned with paintings that startle us with their immediacy and freshness. They were among the first artists to see watercolour as a medium in its own right and not simply as a means of gathering and recording information for oil painting or printmaking.
Melville 'Captured Spy' 1895
Eardley is simply one of the great painters of the 20C. In a life cut short she brought an integrity and sense of urgency to her subjects rare in art. Her paintings, both the landscapes on the Aberdeenshire coast at Catterline and of the Glasgow tenements, challenge and exhilarate us in turn.
Eardley 'Children at a Window'
Format for the Weekend
Arrive in your own time on Friday afternoon
Meet your hosts and lecturer Jeremy Carlisle for pre-dinner drinks and canapés at 6.30pm in the Burns Room.
7.00pm -7.45pm Illustrated introductory talk to the weekend
8.00pm 3 course dinner
7.15am – 9.15am Breakfast in your own time
9.45am Titian talk
11.15am approx Coffee & shortbread in Bistro area
11.45am approx Chardin talk
1.00pm Soup and sandwich lunch
2.00pm -3.15pm Delacroix talk
Free time to explore Kirkcudbright's galleries, shops etc
4.00pm Tea, coffee available in the Bistro.
7.30pm Meet for pre-dinner drinks and canapés in the Burns Room
8.00pm 3 course dinner
7.15am – 9.15am Breakfast in your own time
9.45am Crawhall and Melville talk
11.15am Coffee etc in the Bistro
11.45am Joan Eardley talk
1.00pm Soup and sandwich lunch
Goodbyes and departures
Friday 13th and Saturday 14th November 2014
£229.00 per person, includes Dinner Bed and Breakfast, welcome drink & canapés, coffee breaks, soup and sandwich lunches.
No single room supplement
Booking: Telephone. Selkirk Arms Hotel 01557 330402


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Half of Saudi men lead "lethargic lifestyles," says doctor
The head of the Arab Center for Nutrition has branded Saudi men lazy, junk food-gorging couch potatoes...August 19, 2009 12:40
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The head of the Arab Center for Nutrition has branded Saudi men lazy, junk food-gorging couch potatoes...August 19, 2009 12:40
Increased demand for housekeepers in Saudi Arabia ahead of the holy month is encouraging maids to demand higher pay and better working conditions, reports Arab News.August 19, 2009 9:50
On 2nd August, Dubai Duty Free's Head Office and Distribution Centre was officially inaugurated by H.H. Sheikh Ahmed bin Saeed Al Maktoum, President of Dubai Civil Aviation Authority and Chairman of Dubai Airports.August 18, 2009 12:00
The Orientalist Woven Art, one of the leading carpet galleries in the world, is launching its latest exclusive carpet collection, dedicated to the holy month of Ramadan. The collection, ranges from high quality masterpieces to the most affordable range of rugs and wall hangings. To cater for different tastes and styles to suit a wide range of customers' preferences, the collection comes in different shades, colors, styles and prices.August 18, 2009 12:00
Nayomi launches the Sab'a Bra, the revolutionary new push-up bra. This most recent fashion innovation by Nayomi combines incomparable characteristics with superb design to deliver the best push-up bra in the world.August 18, 2009 12:00
Tiffany & Co., represented by Mohammed Othman Al Moallim Company in Saudi Arabia announced its latest innovation, the new jewelry key collection that comes in trendy and fashionable shapes and styles. Keys from the company's archives inspire the new Tiffany Key Collection. The work of skilled goldsmiths and silversmiths, these exquisitely crafted vintage keys unlock jewelry and keepsake boxes, albums, diaries and steamer trunks, as well as private clubs and country manors. Other archival keys encrusted with gems were designed as brooches and charms, incorporated in a coat of arms or given as gifts to heads of state.August 18, 2009 12:00
Cole Haan, the premier luxury fashion brand offering men's and women's footwear, accessories and outerwear, is taking luxury retail to…August 18, 2009 12:00
IBPC Sharjah launches NewsmagazineThe Indian and Business Professional Council of Sharjah(IBPC) launched their Newsmagazine on India's 63rd Independence Day. The…August 18, 2009 12:00
Crude oil prices fell by...August 17, 2009 12:23


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Posted November 12, 2012 on AP on Fox
Rajon Rondo had 20 points, nine rebounds and 10 assists to lead the Boston Celtics to a 101-95 win over the Chicago Bulls on Monday night. Rondo took advantage of Bulls point guard Nate Robinson for three quarters, helping the Celtics build a 12-point lead on 56-percent shooting. He extended his streak of consecutive games with 10 or more assists to 31, the longest in the NBA since John Stockton had 37 straight between Feb. 27 to Nov. 29, 1989. Brandon Bass led four other Celtics in double figures with 16 points as Boston held off a furious late Chicago rally to snap a five-game losing streak at the United Center. Kevin Garnett had 15 points. Luol Deng led the Bulls with 26 points and 11 rebounds. Joakim Noah added 17 points and 11 boards and led Chicago's fourth quarter rally with nine points. The Celtics became the first team to score 100 points against the Bulls since April 8 of last season, ending a streak that had reached 15 straight games. The Bulls held Boston without a ...
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The Seventh Avenue Heritage Festival officially kicked off Thursday night with a reception in the penthouse of Court Square Towers. Several members of the community were recognized during an awards ceremony.
Republican presidential nominee Mitt Romney is shifting sharply to the political center as he begins to deliver a closing argument aimed at a slice of moderate, undecided voters a month before Election Day.
His performance panned, President Barack Obama is changing his debate strategy against Republican Mitt Romney, aides conceding the president must find a crisper way to sell his agenda and counter his opponent without getting lost in the weeds.
Two people blinded in Washington, D.C., in 2005. Three dead in Virginia in 2006 and three more in Oregon the following year. Twenty-one dead polo horses in Florida in 2009. Earlier this year, 33 people in seven states with fungal eye infections. And now, at least five people dead and 35 sickened with fungal meningitis that has been linked to steroid shots for back pain.
The presidential campaign, hitherto a plod through a torrent of words tedious beyond words, began to dance in Denver. There a masterfully prepared Mitt Romney completed a trifecta of tasks and unveiled an issue that, because it illustrates contemporary liberalism's repellent essence, can constitute his campaign's closing argument.
The first presidential debate of the 2012 election season has come and gone, and most political pundits and news outlets are claiming Mitt Romney as the winner.
If you can't beat em' join 'em. And if you're going to join them, do it in style.
With the deadline for voter registration fast approaching, area circuit court clerks and volunteers alike are urging people to register to vote by Saturday. Those who fail to register by Saturday are not eligible to vote in the November election.
Gov. Phil Bryant labeled the Wednesday event as an opportunity to reach out to the future workforce. Mississippi State hosted "Powering Mississippi in the 21st Century," on Wednesday, and Foster Ballroom in the Colvard Student Union was nearly full during the program, most of the seats occupied by students.
Mississippi University for Women's Gordy Honors College Forum Series presents state senator Sally Burchfield Doty today at 6 p.m. in Nissan Auditorium in Parkinson Hall on the MUW campus.
A Columbus man is currently in the custody of the Lowndes County Adult Detention Center after allegedly committing an armed robbery on Tuesday.
Some New Orleans residents and city officials are pushing back against tour operators who bus out-of-towners into the city's Lower 9th Ward, where Hurricane Katrina unleashed a wall of water that pushed homes off foundations and stranded residents on rooftops when the levees failed.
A small company won a $10 million federal grant to expand wireless service in one of Alabama's most isolated regions, a five-county area west of Montgomery where it's sometimes impossible to make a cellphone call.
In Chicago, a bustling urban metropolis where skyscrapers are as likely to sprout up as anything a farmer might plant, someone decided there was just enough room to grow something a little more organic: Marijuana.
Alex Al-Quawwas wants to expand his business with a hookah lounge, where people would be able to smoke a non-tobacco product using a hookah.
The U.S. economy is looking more resilient, thanks in part to encouraging signs for the two most expensive purchases most Americans make: cars and homes.
Americans are expected to spend more during what's traditionally the busiest shopping season of the year, but they're not exactly ready to shop 'til they drop like they have been in the past two years.
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1. Columbus KiOR facility sold to Georgia company COLUMBUS & LOWNDES COUNTY
2. Arrest report 10-6-15 COLUMBUS & LOWNDES COUNTY
3. Prosecutor appeals directed verdict in Vaughn DUI case STARKVILLE & OKTIBBEHA COUNTY
4. Arrests made in West Point shooting death AREA
5. Yokohama holds grand opening ceremony AREA


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December 6, 2012
Harry Winston says Diavik Diamond Mine full-year target production 7.1M carats
Diavik Diamond Mine's full-year target production is expected to be approximately 7.1M carats from the mining of 2.1M tonnes of ore and the processing of 2.0M tonnes of ore. The decrease in carats from the original plan is primarily due to deferring the processing and recovery of lower value carats from the re-processed rejects in favour of processing underground ore containing higher valued carats. A new mine plan and budget for CY13 is under final review by Rio Tinto (RIO) and the company. The plan for CY13 foresees Diavik Diamond Mine production of approximately 6M carats from the mining and processing of approximately 1.6M tonnes of ore with a further 0.2M tonnes processed from stockpiled ore from CY12. Mining activities will be exclusively underground. Included in the estimated production for CY13 is approximately 0.6M carats from RPR and 0.1M carats from the improved recovery process for small diamonds.
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Usher Celebrates 34th Birthday With Tom Cruise, Ridley Scott
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Talk about friends in high places.
Usher, who turned 34 on Sunday, celebrated his birthday over the weekend in the company of Hollywood royalty. Dining at Scott's Restaurant in Mayfair, London, the night before his big day, the multiplatinum R&B singer Instagrammed a photo of himself sandwiched between pals Tom Cruise and Sir Ridley Scott, the Oscar-nominated director of films including "Gladiator," "Alien" and "Prometheus."
PHOTOS: More surprising celebrity BFFs
"Just an average pre-birthday for @Howuseeit...thank you Tom and Ridley for dinner lots of laughs and good conversation," he tweeted, referring to his Instagram username.
Usher has had a busy few months.
PHOTOS: Tom Cruise, Will Smith, and other Hollywood bromances
On Aug. 24, after a heated legal battle with ex-wife Tameka Foster, the star was awarded primary custody of his sons Usher Raymond V, 4, and Naviyd Raymond, 3. As a result, he decided to postpone his Euphoria tour, originally slated to kick off in January, until next fall. He plans to use the time off to focus on his kids.
"I truly appreciate and am grateful for your support while I take this time to focus on my children and continue to evolve with my fans," he said in a statement on his website. "Evolve or evaporate."
As part of that evolution, the chart-topper will also be prepping for his role as a mentor on Season 4 of "The Voice." NBC recently announced that Usher and Shakira, 35, would join the show as replacements for Cee Lo Green, 38, and Christina Aguilera, 31.
Hollywood's Nastiest Custody Battles
Usher Awarded Primary Custody of Two Sons Over Ex-Wife, Tameka Foster
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I visited the bar(s) for a colleague's leaving party. There are several bars in one location and the one we were in had good service, decent bar snacks (chicken, ships etc) and nice beers. Prices were reasonable.
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Gannaway, Masterson to wed
Mr. and Mrs. Jeff Montgomery Gannaway of Tunica are pleased to announce the engagement of their daughter, Ann Clark Gannaway, to Mr. Chester Warren Masterson, III of Jackson.
Mr. Masterson is the son of Ms. Karen Tullos Masterson of Jackson and Mr. Chester Warren Masterson, Jr. of Vicksburg.
He is the grandson of Mr. and Mrs. Ben Harrell Tullos, Sr. of Madison and Mrs. Chester Warren Masterson, Sr. and the late Dr. Masterson of Vicksburg.
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Huntington woman talks about vows of silence
Jean Kelly of Huntington discusses her work as the executive director of the Interfaith Nutrition Network, a nonprofit that helps needy Long Islanders - and she discusses her commitment to periodically take vows of silence. Videojournalist: Erin Geismar (March 26, 2012)
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Port Jeff students learn about chainsaw art Under the helmet: Inside LI football helmets FDR's son's home for sale in Woodbury 3 injured in police patrol car crash Crash closes Sunrise Highway in East Patchogue Off-duty Suffolk County officer helps revive hockey player North Amityville gas station attendant robbed, say cops One dead after bar dispute 'Blessing of the Animals' in Brentwood Making apple cider in Northport Tom Cutinella anniversary vigil on football field Coastal concerns for Fire Island as Joaquin nears


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Do you ever wonder what happens to all those corrugated metal shipping boxes? Is there some graveyard where obsolete cargo containers go to be piled into a rusty, sad mountain of metal? Well, loo…62 comments
By Lloyd Alter, TreeHugger TreeHugger has been covering tiny houses for years; I even own one, the remains of a previous career trying to promote the idea of the tiny house. Notwithstanding the s…40 comments
Habitat for Humanity is addressing a global housing crisis one home at a time. According to the non-profit, Habitat for Humanity: "About 1.6 billion people live in substandard housing and 100 million …45 comments
After living in a 600-square-foot studio apartment for 23 years, Ken and Linda Bolton bought their first home in 2000. "I was seeking three bedrooms, a dining room and lots of windows," Linda says. Sh…73 comments
For the most part, Victoria Gazeley has everything she needs in the 650-square-foot restored homesteader's cabin in coastal British Columbia that she shares with her 7-year-old son. The one thing she …45 comments
My kids tagged along when we photographed Quietude, Denise Franklin's 280-square-foot cottage in the Okanagan mountains near Oliver, British Columbia, a couple summers ago for Natural Home & Garde…114 comments
Ever dream about creating the perfect eco-house? The importance of greening our homes to save energy and the planet has become more and more mainstream. I've been following the tiny house movement, an…91 comments
Jay Shafer is a designer of tiny houses, so small some might laugh when they first see the 89 square-foot house on a trailer, but there is something undeniably practical and sane about what he is doin…303 comments
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Sports Star, Astronaut, Doctor, maybe but the above would not go over
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