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Research article | Open | Published: 29 December 2018
Clinical phenotypes and biologic treatment use in juvenile dermatomyositis-associated calcinosis
Amir B. Orandi ORCID: orcid.org/0000-0002-3720-24021,2,
Vikas R. Dharnidharka3,
Noor Al-Hammadi4,
Kevin W. Baszis2 &
for the CARRA Legacy Registry Investigators
Few risk factors have been identified for the development of calcinosis among patients with Juvenile Dermatomyositis, and currently no clinical phenotype has been associated with its development. We analyzed a large database of patients to further elucidate any relationships among patients with and without calcinosis.
The CARRA legacy registry recruited pediatric rheumatology patients from 55 centers across North America from 2010 through 2014, including over 650 subjects with Juvenile Dermatomyositis. We compared the demographic characteristics, clinical disease features and treatment histories of those with and without calcinosis using univariate and multivariate logistic regression.
Of the 631 patients included in the analysis, 84 (13%) had a current or prior history of calcinosis. These patients were statistically more likely to have longer durations of disease prior to diagnosis and treatment, have lipodystrophy and joint contractures, and to have received intravenous immune globulin or rituximab as treatments.
Calcinosis is found more often in patients with prolonged active disease, severe disease, and certain clinical features such as lipodystrophy and joint contractures. When these factors are combined with other known associations and predictors, groups of at-risk patients can be more effectively identified, treated and studied to improve overall outcomes.
As the most common inflammatory myopathy of childhood, Juvenile Dermatomyositis (JDM) affects 3.2 per million children annually in the United States [1]. Before the widespread use of glucocorticoids, followed by disease-modifying anti-rheumatic drugs (DMARDs), JDM was fatal in one-third of cases [2,3,4]. More recent studies have shown mortality as low as 3.1% [5] while simultaneously highlighting persistent morbidity from active disease or its sequelae [6,7,8]. An enigmatic source of morbidity comes from calcinosis, the dystrophic deposition of the mineral calcium hydroxyapatite in the skin, soft tissues or muscle, which is reported to occur in approximately 40% of patients [9]. When surveyed in 2016 regarding their experience and approach to assessing and treating JDM calcinosis, less than 20% of pediatric rheumatologists have treated more than 10 cases. In addition, the majority who have such experience have practiced for more than 20 years. [10].
There have been many studies attempting to identify risk factors or associations of calcinosis in JDM patients in order to further define the at-risk patient population. Actionable risk factors previously identified include a delay to treatment and/or prolonged disease duration [5, 11, 12] and initial treatment intensity [13, 14]; prognostic factors included race [15,16,17], male sex [15], underlying cardiac disease [18, 19], presence of joint contractures [18], and presence of certain myositis-specific antibodies [20, 21]; genetic risks were also identified [22, 23]. However, in some large cohorts, no risk factors are identified [24]. Due to the rarity of JDM as a whole, and with calcinosis occurring in less than half of patients, there have been few studies of large numbers of patients with calcinosis. Lacking among all of these studies is a clinical phenotype of patient disease features that might also be associated with the development of calcinosis, apart from prolonged or severe disease, which has many connotations depending on the publication. Further, regarding treatment, much attention has been paid to the amount and duration of glucocorticoid use [25,26,27], but there has been no assessment made of whether the use of biologic treatments, now widely used, are associated with calcinosis. Our aim was to address these questions by analyzing a large patient registry of JDM patients with assessments of clinical features and treatment histories, including those who developed calcinosis during the course of follow-up.
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed a multicenter registry for pediatric rheumatologic diseases across North America. Patients were enrolled from May 30, 2010 through October 31, 2014 from 55 CARRA centers. JDM was among the diseases included in the registry, and any patients whose disease began before 18 years of age and were less than 21 years of age at the time of enrollment were eligible for inclusion. All JDM patients must have met the Bohan and Peter criteria for diagnosis, modified to allow magnetic resonance imaging as an acceptable diagnostic modality [28].
All data were submitted by the enrolling physician at each site after collecting clinical data using report forms for general information, demographics, functional and quality-of-life measures and JDM-specific information at baseline and follow-up visits. At baseline (the time of registry enrollment), the presence of several disease manifestations was assessed (present, absent or not assessed), including proximal muscle weakness (designated mild, moderate or severe), characteristic disease rashes, lipodystrophy, skin ulceration, periungal telangiectasias and contractures (not specified as due to muscle or joint disease). There was also documentation of presence or absence of other disease features (current, past or never), including calcinosis, small or large joint arthritis, dysphagia or dysphonia and organ involvement (cardiac, gastrointestinal or lung). At follow-up visits, these same clinical features were documented if present or absent. At enrollment, the patient's history of biologic medication use was assessed by current or prior use, and at follow-up visits, it was assessed if any biologic medication had been used in the visit interval. Patient data were kept in a centralized database by CARRA and after study approval were transmitted as a coded, deidentified dataset under code access agreement to the study team. This study was exempt from the Washington University School of Medicine institutional review board by not constituting human subject research.
All analyses were performed using SAS version 9.4 (SAS Institute Inc) and R version 3.3.1 (R Project for Statistical Computing). Any patients lacking requisite data in calcinosis were excluded. A cross-sectional analysis of baseline data in all JDM patients was performed comparing those with any history (current or past) of calcinosis to those without (never) in respect to demographic characteristics, clinical and disease features, and treatment with biologic agents and glucocorticoids. To calculate the duration of symptoms prior to treatment, the difference between symptom onset date and first rheumatology visit date was used, measured in months. Due to small respective numbers of each form of organ involvement (i.e. cardiac arrhythmia), a composite measure combining all different forms of organ toxicity (i.e. cardiac, pulmonary and gastrointestinal) was also used. For similar reasons, different tumor necrosis factor (TNF)-alpha inhibitors and interleukin-1 inhibitors were grouped as single entities for the purpose of analysis. Information on glucocorticoid treatment was collected in the registry by documenting only current or prior receipt of intravenous pulse steroids and/or systemic daily long-term use of specified durations. No dosages or intervals were recorded. In order to study possible effect of high or low glucocorticoid exposure, selected patients were grouped for the purpose of analysis. A patient with high steroid exposure was defined as one with a current or prior history of intravenous pulse steroids and current or prior use of daily systemic corticosteroids of at least one-month duration. Differences between patients with and without calcinosis were analyzed with t-test or Mann-Whitney-U tests for continuous variables as appropriate, while comparisons for categorical variables used Chi-square or Fisher's exact tests as appropriate. Statistically significant measures at the alpha level of 0.05 on univariate analyses were included in multivariate logistic regression modeling. Stepwise selection method during multivariate logistic regression modeling was used to adjust for collinearity of certain clinical features, where a variable had to be significant at the 0.25 level to be entered into the model and significant at 0.15 to stay. At the following step, the final model included variables significant at 0.05. A Forest Plot using R program was performed to illustrate the odds ratio and associated 95% confidence interval that were significant in the logistic regression model.
A total of 654 patients with JDM were enrolled in the CARRA legacy registry. Twenty-three patients were excluded who lacked information on calcinosis, including five patients with follow-up data but no information at baseline. The remaining 631 were included in analysis, with 84 patients (13.3%) having a current or prior history of calcinosis at the time of enrollment. The registry cohort included 454 females (72%) and 177 males (28%) with a median age at diagnosis of 5.6 years. Caucasian race comprised 82% of patients, while Hispanic ethnicity represented 15% of patients, and African-American, 13%. The majority of patients were categorized as 'probable' JDM, which was used to define 490 patients (78%), while 48 (7.6%) were categorized as definite. Only nine patients (1.4%) were designated as amyopathic, and the remaining 13% had no selected category. Across the entire cohort, 38% had current or prior treatment with a biologic medication (Table 1).
Table 1 Cohort characteristics, n = 631
Clinical disease features
When comparing those with a history of calcinosis to those without, there were statistically significant differences in the proportions of the two groups for several demographic and clinical features (Table 2). There was no difference between groups in regards to cardiac, lung or gastrointestinal involvement, but when these events were combined as a single composite feature, "any organ involvement", the differences were statistically significant. In univariate analysis, statistical significance was maintained for characteristics of male sex (OR 1.811, 95% CI 1.123–2.919), time to diagnosis (OR 1.029, 95% CI 1.016–1.043) and African-American race (OR 2.264, 95% CI 1.270–4.038). For other clinical disease features, lipodystrophy (OR 5.993, 95% CI 2.588–13.874), joint contractures (OR 5.343, 95% CI 2.964–9.635), cutaneous ulcerations (OR 3.748, 95% CI 1.787–7.862), Gottron's or heliotrope rashes (OR 1.754, 95% CI 1.099–2.800), V or shawl sign (OR 2.410, 95% CI 1.083–5.361) and organ involvement (OR 2.506, 95% CI 1.127–5.573) also maintained significance (Table 2) and were included in multivariate analysis.
Table 2 Clinical characteristics by history of calcinosis
Treatment with biologics
In the overall cohort, 242 (38.4%) patients experienced current or prior use with a biologic agent. Intravenous immune globulin (IVIG) was the most common with 225 (35.6%) patients exposed followed by anti-TNF-alpha therapy with 35 (5.5%) patients. Etanercept comprised the majority of anti-TNF-alpha therapy with 22 patients reporting use, representing 63% of all anti-TNF-alpha therapy. Rituximab was used in 26 (4.1%) patients. When comparing patients with a history of calcinosis to those without, statistical significance between groups was maintained on univariate analysis for all treatments, except anti-IL1 agents as follows: Rituximab (OR 6.345, 95% CI 2.825–14.245), IVIG (OR 2.353 95% CI 1.479–3.743), anti-TNF-alpha (OR 3.797, 95% CI 1.812–7.960) and abatacept (OR 13.317, 95% CI 1.194–148.514). All were included in multivariable analysis except abatacept, since it was only used in three patients overall, and despite positive odds ratio had an extremely wide confidence interval (Table 3).
Table 3 Treatment exposure by history of calcinosis
In the multivariable analysis including clinical features and treatments, the only predictors of association with calcinosis were increased time to diagnosis (OR 1.029, 95% CI 1.013–1.045), lipodystrophy (OR 3.038, 95% CI 1.014–9.106), joint contractures (OR 4.499, 95% CI 2.106–9.609), rituximab use (OR 3.955, 95% CI 1.551–10.089), and IVIG use (OR 1.891, 95% CI 1.062–3.366), as shown in Fig. 1.
Results of multivariate logistic regression analysis. Risk factors and event rates among patients with and without calcinosis are shown with p-values. Forest plot displays odds ratios and associated 95% confidence intervals of multivariate logistic regression
Outcomes of calcinosis
Of the 631 patients included in analysis, only 422 had at least one follow-up visit. We reviewed the history of calcinosis in these 422 patients through the first follow-up visit. At baseline enrollment, 356 (84%) patients never had calcinosis and did not develop it through the first follow-up visit. A total of 42 patients had calcinosis present at the time of registry enrollment, and in 11 (26%) of these patients, the calcinosis resolved by the first follow-up visit, while in 31 (74%) patients, the calcinosis persisted. There were 14 patients with a prior history of but no calcinosis present at the time of enrollment. Three of these patients would develop a recurrence by the first follow-up visit.
Ten patients (2.5%) who never had calcinosis at the time of baseline enrollment, developed calcinosis by the first follow-up. The median age of JDM disease onset in these patients was 7 (IQR 4.5–8.2) with a median age at first follow-up (development of calcinosis) of 10.6 years (IQR 9.8–12.4). It should be noted that age of JDM disease onset could be different from age of diagnosis, and age of baseline enrollment. Eight patients were female. Six patients were Caucasian, three patients African-American and one patient mixed Caucasian and Hispanic. At the time of baseline enrollment, one patient had lipodystrophy, while one patient had joint contractures. For patients with available data, most (7/9, 78%) had previously received IV pulse steroids, and 7/9 (78%) were actively receiving daily long-term glucocorticoids for at least 1 month's duration. Four patients (50%) had previously received IVIG and 4/8 (50%) were actively receiving it. One patient had previously received rituximab (and also previously received IVIG), while one patient was actively receiving rituximab but had never received IVIG. None of the 10 patients had ever received anti-TNF-alpha therapy, abatacept or interleukin-1 inhibitors.
Previous studies have highlighted differences between patients with calcinosis and those without. Duration of active JDM disease has been studied and described in two ways: the duration of symptoms prior to initial diagnosis and treatment, and as chronically active disease despite treatment. These two scenarios are not mutually exclusive. When expressed as the time until diagnosis and treatment, increased symptom duration has been shown to be a risk factor for the development of calcinosis in some studies [5, 11, 18, 29, 30] but not in others [8, 19, 24], including a cohort with a high frequency of calcinosis. When the duration of active disease is expressed as chronically active disease despite treatment (i.e. cumulative disease duration), an association with calcinosis is also found in the studies that examined this feature [5, 6]. The combination of these assessments has led to the understanding that prolonged and/or severe disease activity is a risk factor for calcinosis. This understanding has subsequently been tested, with some evidence that early induction of remission can prevent calcinosis [13, 14]. Myositis antibodies are now widely used to guide prognosis and predict certain complications. In UK cohorts, calcinosis was associated with positive anti-MJ antibodies [20, 21], but this was not replicated in in a North American cohort, in which calcinosis occurred with equal frequency in patients with anti-p155/140, anti-MJ and negative serology [31]. African race, despite a low frequency of patients in all JDM cohorts, has been shown to be a risk factor for calcinosis [15,16,17]. Previously, the only non-demographic clinical features that were associated with calcinosis were cardiac disease [19] and joint contractures [18].
To our knowledge, our study includes the largest number of JDM patients with calcinosis collected and analyzed as a single cohort. Compared to other international series, our demographic characteristics of sex, age at onset, and JDM classification types are similar [5,6,7,8, 16, 24, 29]. We found no association that the age of JDM onset is associated with calcinosis. Male sex was associated with calcinosis on univariate analysis but did not hold significance on multivariable analysis. Our study demonstrated, as others have, that a delay in diagnosis and treatment is associated with the development of calcinosis; however, the effect in our study was small (OR 1.029, 95% CI 1.013–1.045). In addition, we showed that receiving IVIG or rituximab are more strongly associated with ever having calcinosis, and with higher odds ratios (OR 1.891, OR 3.955 respectively) than those with treatment delays. This effect was not seen with our variable of high steroid exposure. Given that IVIG and rituximab are typically reserved for those who fail standard treatment, we suspect those patients had more severe and/or prolonged active disease despite treatment. Clearly, untreated disease represents a risk for developing calcinosis, as was demonstrated in early studies with less effective treatments [2]. A delay in treatment imparts this same risk, and based on the intermittent association of this factor with calcinosis in various studies, this suggests that the effect may possibly be mitigated with more effective treatment, in addition to more timely treatment. Perhaps this implies that at even greater risk are the types of disease courses which are chronically active and difficult to control. Many studies, including those focusing on myositis antibodies are attempting to identify the pathophysiological mechanisms underlying these differences and therefore predict which patients might be at risk of calcinosis. If reliable, such predictions would encourage the development of screening techniques and potentially inform treatment approaches. In our study, we found that joint contractures (OR 4.499, 95% CI 2.106–9.609) and lipodystrophy (OR 3.038, 95% CI 1.014–9.106) were both independently associated with developing calcinosis, the latter of which to our knowledge has not been previously reported. Cutaneous ulcerations and any organ involvement (i.e. cardiac, pulmonary or gastrointestinal) were also associated with calcinosis on univariate analyses but did not hold significance in multivariate analysis. These associations may not have been identified in prior studies due to the small numbers of patients with calcinosis as a whole in those studies. Additionally, as collected in the legacy registry, the presence or absence of disease features were assessed simply as current, past or never without reference to chronology. Calcinosis, particularly across a joint may lead to joint contractures [9], which may partially explain this association. Previously, calcinosis was also identified as a predictor for lipodystrophy with affected areas often overlying areas of calcinosis or panniculitis [32]. By reviewing the limited follow-up data in the registry, we also describe that calcinosis occurs infrequently in this cohort over a short time period (2.5% of patients with one follow-up visit), but calcinosis tends to persist or recur once it has developed. It is also noted that in the 10 patients who developed calcinosis, most had received IVIG and/or rituximab suggesting they had either severe or refractory disease, but none of these patients had received anti-TNF-alpha therapy, since monoclonal antibody forms have been shown to be effective against JDM disease activity and calcinosis [33].
The limitations of our study include the retrospective methodology and that patients enrolled in this registry were a convenience sample with varying disease durations at the time of enrollment. Prior histories of treatment and/or complications are subject to recall bias by patients/parents and sufficient documentation at the many respective enrolling centers. Information on calcinosis itself was limited only to its presence or absence without further assessment of phenotype or complications such as infection. There was also no information on whether treatments received by patients were specifically intended for calcinosis or for other JDM disease activity. Additionally, information on testing of myositis-specific and myositis-associated antibodies was not collected. Further, there is inconsistent and relatively few follow-up dates, as the funding for this registry was limited to a short duration of data capture. Given these limitations, however, the CARRA legacy registry has provided important information about pediatric rheumatic diseases and JDM. Many of these limitations have been addressed in the newly created CARRA registry which began enrolling patients in 2015 with plans for several years of prospective follow-up. Apart from the full rationale and methodology already published [34], there are specific improvements in the data capture for JDM and calcinosis that address many of these limitations.
The pathogenesis and treatment approach for calcinosis remains a frontier of research in Juvenile Dermatomyositis. Identifying patients at risk for the complication is a critical step to improving treatment outcomes by focusing research efforts. From studying a large registry of patients, we confirm prior reports that a delayed time to diagnosis and treatment, joint contractures and organ disease are associated with calcinosis, and we also found that lipodystrophy is similarly associated. More aggressive therapy, namely IVIG and rituximab, in our study cohort is also associated with calcinosis which may reflect chronically active or refractory disease.
Childhood Arthritis and Rheumatology Research Alliance
CHAQ:
Childhood health assessment questionnaire
DMARDs:
Disease-modifying anti-rheumatic drugs
IVIG:
Intravenous immune globulin
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We would also like to thank all participants and hospital sites that recruited patients for the CARRA Registry. The authors thank the following CARRA Registry site principal investigators and research coordinators: L. Abramson, E. Anderson, M. Andrew, N. Battle, M. Becker, H. Benham, T. Beukelman, J. Birmingham, P. Blier, A. Brown, H. Brunner, A. Cabrera, D. Canter, D. Carlton, B. Caruso, L. Ceracchio, E. Chalom, J. Chang, P. Charpentier, K. Clark, J. Dean, F. Dedeoglu, B. Feldman, P. Ferguson, M. Fox, K. Francis, M. Gervasini, D. Goldsmith, G. Gorton, B. Gottlieb, T. Graham, T. Griffin, H. Grosbein, S. Guppy, H. Haftel, D. Helfrich, G. Higgins, A. Hillard, J.R. Hollister, J. Hsu, A. Hudgins, C. Hung, A. Huttenlocher, N. Ilowite, A. Imlay, L. Imundo, C.J. Inman, J. Jaqith, R. Jerath, L. Jung, P. Kahn, A. Kapedani, D. Kingsbury, K. Klein, M. Klein-Gitelman, A. Kunkel, S. Lapidus, S. Layburn, T. Lehman, C. Lindsley, M. Macgregor-Hannah, M. Malloy, C. Mawhorter, D. McCurdy, K. Mims, N. Moorthy, D. Morus, E. Muscal, M. Natter, J. Olson, K. O'Neil, K. Onel, M. Orlando, J. Palmquist, M. Phillips, L. Ponder, S. Prahalad, M. Punaro, D. Puplava, S. Quinn, A. Quintero, C. Rabinovich, A. Reed, C. Reed, S. Ringold, M. Riordan, S. Roberson, A. Robinson, J. Rossette, D. Rothman, D. Russo, N. Ruth, K. Schikler, A. Sestak, B. Shaham, Y. Sherman, M. Simmons, N. Singer, S. Spalding, H. Stapp, R. Syed, E. Thomas, K. Torok, D. Trejo, J. Tress, W. Upton, R. Vehe, E. von Scheven, L. Walters, J. Weiss, P. Weiss, N. Welnick, A. White, J. Woo, J. Wootton, A. Yalcindag, C. Zapp, L. Zemel, and A. Zhu.
Washington University, Institute of Clinical and Translational Sciences, Core Usage Funding, Just-in-Time Grant, PI: Dr. Vikas Dharnidharka, via NIH grant NCATS UL1TR000448
Eunice Kennedy Shriver National Institute of Child Health and Development, T32 HD043010101
Washington University, Institute of Clinical and Translational Sciences, Mentored Training Program in Clinical Investigation via NIH grant NCATS UL1TR000448
The CARRA Legacy Registry was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award Number RC2AR058934. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The CARRA Legacy Registry was also supported by CARRA, Friends of CARRA, the Arthritis Foundation, and the Duke Clinical Research Institute.
The data that support the findings of this study are available from CARRA, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.
Division of Pediatric Rheumatology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55902, USA
Amir B. Orandi
Division of Pediatric Rheumatology, Department of Pediatrics, St. Louis, MO, USA
& Kevin W. Baszis
Division of Pediatric Nephrology, Department of Pediatrics, St. Louis, MO, USA
Vikas R. Dharnidharka
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
Noor Al-Hammadi
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, M. Gervasini
, D. Goldsmith
, G. Gorton
, B. Gottlieb
, T. Graham
, T. Griffin
, H. Grosbein
, S. Guppy
, H. Haftel
, D. Helfrich
, G. Higgins
, A. Hillard
, J. R. Hollister
, J. Hsu
, A. Hudgins
, C. Hung
, A. Huttenlocher
, N. Ilowite
, A. Imlay
, L. Imundo
, C. J. Inman
, J. Jaqith
, R. Jerath
, L. Jung
, P. Kahn
, A. Kapedani
, D. Kingsbury
, K. Klein
, M. Klein-Gitelman
, A. Kunkel
, S. Lapidus
, S. Layburn
, T. Lehman
, C. Lindsley
, M. Macgregor-Hannah
, M. Malloy
, C. Mawhorter
, D. McCurdy
, K. Mims
, N. Moorthy
, D. Morus
, E. Muscal
, M. Natter
, J. Olson
, K. O'Neil
, K. Onel
, M. Orlando
, J. Palmquist
, M. Phillips
, L. Ponder
, S. Prahalad
, M. Punaro
, D. Puplava
, S. Quinn
, A. Quintero
, C. Rabinovich
, A. Reed
, C. Reed
, S. Ringold
, M. Riordan
, S. Roberson
, A. Robinson
, J. Rossette
, D. Rothman
, D. Russo
, N. Ruth
, K. Schikler
, A. Sestak
, B. Shaham
, Y. Sherman
, M. Simmons
, N. Singer
, S. Spalding
, H. Stapp
, R. Syed
, E. Thomas
, K. Torok
, D. Trejo
, J. Tress
, W. Upton
, R. Vehe
, E. von Scheven
, L. Walters
, J. Weiss
, P. Weiss
, N. Welnick
, A. White
, J. Woo
, J. Wootton
, A. Yalcindag
, C. Zapp
, L. Zemel
& A. Zhu
AO authored the manuscript. AO and KB made substantial contributes to study design, acquisition data and interpretation of statistical analysis. VD made substantial contribution to study design, co-acquisition of funding, interpretation of data and analyses. NA performed statistical analysis and made substantial contributions to study design and interpretation of data. All authors provided critical edits and approved the manuscript for publication.
Correspondence to Amir B. Orandi.
This study was exempt from review by the Washington University Institutional Review Board by not constituting human subject research.


Outgoing Defense Secretary James Mattis said goodbye to his colleagues at the Pentagon Monday in a three-paragraph farewell letter.
Mattis had originally planned to step down in February, but Trump announced on Dec. 23 that Deputy Secretary of Defense Patrick Shanahan would take over the top spot at the Pentagon Monday night.
Shanahan is a long-time Boeing executive, working for the defense contractor for more than 30 years before moving over to the Defense Department a little more than 17 months ago. He served as Mattis' second in command at the Pentagon, concentrating on internal reforms, budgetary matters and the Space Force.


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Program: Access to education
Project: Pastoral Education and Integrated Field School in South Sudan
Pastoralism is a form of livestock grazing practiced by nomadic people who move around with their herds. Today, over 200 million people around the world rely on pastoralism to earn their livelihoods. At least 65% of the population in South Sudan are a part of agro-pastoralist communities. The pastoralist communities in South Sudan are marginalized with limited access to basic services such as education and livelihood support activities. The pastoralist mobility in search of pastor and water for their cattle is a key strategy of pastoral livelihood systems. This mobility has placed pastoralists beyond the reach of education and extension services. As most service provision models are designed for sedentary living, pastoralists in the cattle camps are left out from receiving basic services and the opportunity to engage in diverse livelihood activities. Institutional arrangements to provide such services are also lacking due to limited government resources.
In recognition of this challenge faced by pastoralist communities, IIRR together with Norwegian People's Aid in partnership with FAO and UNESCO with funding from European Union piloted the Integrated Pastoral Field School. This integrated model is a viable alternative education to provide pastoralists with livelihood and learning opportunities. The target learners in each cattle camp are children aged 6-16 years, youth, and adult learners. The program has so far benefited over 2,000 children, 640 youth, and 480 adults in cattle camps in South Sudan.
The Mobile Pastoralist Education Curriculum is organized into three levels and imparts knowledge on basic literacy and numeracy. Each level is designed to last 9 months and a child who attains Level 3 is equipped to join mainstream primary school. For adults, the education is more hands-on. Adults in the camp learn by doing. Topics are connected to their livelihoods such that experience with livestock management is core to their curriculum. Alternative means of income generation and livelihood diversification is also integrated into the program.
The program is scheduled to run up to March 2021 but due to COVID-19 and the challenges of securing personal protective equipment during this time, the program was halted for 4 months in 2020. IIRR is negotiating extending the program until August 2021 to compensate for this interruption. To ensure the pastoral communities' long-term success and the continued education of children after completion of the program, IIRR is lobbying the government to maintain the cohort for another 2 years so that learners can be supported as they enter main-stream primary education. IIRR also plans to introduce a skills program for those who will have attained basic literacy and numeracy to further develop their life skills.

redpajama_set_name: RedPajamaCommonCrawl


Nilla White Special Edition, blonde beer enriched with red hops combined with white chocolate and Tahiti vanilla pods. Really special! It will be the taste that will remain in your mouth !!!
All Porky's Flavor E-Liquids come in 60mL 0mg, 3mg, 6mg, & 50 mL Mix & Shake - 0mg nicotine.


I have a two month old, 42 gal tank with four cichlid's. My current GH (general hardness) is 90ppm with KH of around 300ppm. This is after my last water change. I have had my GH as far as 120ppm. I have been told to add marine salts to raise the GH. This does not seem to work. I have added and added. I am just afraid that I will add too much???
The good news is that my PH, KH, Ammonia, Nitrate are all excellent. My fish seem to be happy.... except for the "Chicken Dance" they do every so often. Fish look very heathy and eat like crazy.
Is there a way to get my GH up safely to at least 200ppm? How much salt can my fish tank take?
Sounds like your tap just happens to have a much higher KH than GH (since when you changed the water the GH went down). As you've discovered, sodium alone has no effect on GH (or on KH, for that matter).
Since your fish are doing well and your pH is good and stable (high KH), I wouldn't be concerned about trying to adjust the parameters so much. I'm assuming you have Rift Lake cichlids. If that's the case, they'll nevertheless do ok in lower GH water, as you've already seen. Softer water might affect spawning somewhat; but that aside, I think they'll remain just fine with they get from the tap.
Besides, I have no idea about how to increase GH without affecting the KH, except maybe add calcium chloride (which I probably wouldn't do if I were dealt those parameters and my fish were doing well).
Thanks for the info. This eases my mind and helps me understand more. I am not looking to breed or anything like that. I will look into getting some good hard water for the next water change (just to trying to put the fish into there regular environment). My first goal is maintaining this healthy tank.
I actually do not know exactly what type of Cichlids I have… after reading your comments and reviewing other threads; I need to do some research and find out more about my fish and what they exactly are? Do you recommend a site with good pictures for examples?
Because you're striving for hard water, I had assumed you keep African cichlids (from the Great African Lakes, not the riverine species).
By the way, are the parameters you cite indeed pretty much those of your tap? Marine salts contain carbonates (which don't affect GH but rather KH), hence the question.


Maybe I just don't remember -- did newspapers sell stuff like this after Bush won in 2000 and 2004?
The Lexington Herald-Leader is doing the exact same thing.
So is the Charlotte Observer.
Hey, why not? Revenue is good. Regardless of your politics this was an historic election. Bush's elections in '00 and '04 didn't trigger massive single copy sales either. Besides, if you are still smarting because McCain lost you can take solace in rolling your mouse over the president-elect.
The Star-Telegram is too. To be fair, though, Bush's election doesn't have nearly the historical significance as Obama's - whether you agree with the decision or not.
Yep, thats right. First Marxist President. Personally, I am betting on the historical significance of the way he leaves office. I won't buy anything from McClatchy though. They won't be in business.
11:41 Get over it. Don't collect you pay check either.
I'll buy a front page of my paper on Jan 21 that shows George Bush getting on a plane for Texas....now that's something worth collecting!


Training is one of LAC's 7 Ministry Networks.
We are committed to training the next generation of pastors, teachers, and workers in Latin America and the Caribbean to lead the body of Christ in obedience to God's word and to His commands. From the beginning, the preparation national leaders has been among our highest priorities. This work extends from the level of local Sunday school and personal discipleship to pastoral training in Bible schools established all across the continent.
The continued emphasis on education and training has prepared a generation of educational leaders and in all areas of Latin America and the Caribbean. National educators are joining and, in many cases, leading the task of training new pastors and future educators.
LAC offers pastoral continuing education programs, and most national ministry leaders have been through the Latin America Advanced School of Theology or the Caribbean School of Theology. Regional teacher training and certification summits held up to three times a year are preparing yet another generation of educators. The theme of these schools has always been knowledge and fervor. The Facultad de Teologia is the masters level continuing education program. The leadership of this school has the long term goal of preparing doctoral level faculty and Latin American authors who will produce the texts for the next generations.
Explore opportunities to join training efforts by clicking the link below.


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Marup is a settlement in Sarawak, Malaysia. It lies approximately  east-south-east of the state capital Kuching. Neighbouring settlements include:
Bukong  south
Munggu Tajau  east
Sungai Meniang  east
Selindong  east
Engkilili  northeast

References

Populated places in Sarawak

redpajama_set_name: RedPajamaWikipedia


text:
"That Damned Fellow Upstairs"
by Edmund Pearson
Mr. Pickwick knew an old man who said that the rooms in the Inns of Court were 'queer old places' — odd and lonely.
'Not a bit of it!' said a sceptical friend.
Then the sceptic, who lived by himself in one of these rooms, died one morning of apoplexy, as he was about to open his door. Fell with his head in his own letterbox, and lay there for eighteen months. At last, as the rent was not being paid, the landlords had the door forced, 'and a very dusty skeleton in a blue coat, black knee-shorts and silks, fell forward in the arms of the porter who opened the door'.
Years after Mr. Pickwick's adventures were over, entrance was one day forced into another queer old room in a London house, and, with a tremendous clatter, out tumbled another skeleton, of a still stranger kind.
The noise it made was not heard in America, since we were completely absorbed, that summer, in the first Battle of Bull Run. The story would be forgotten in England today, were it not for the admirable essay published seven years ago by the late Sir John Hall, Bart. This gentleman is respected by all those who appreciate scholarly descriptions of curious events. It is probable, however, that of all who see my retelling of the tale, only experts like Messrs. Alexander Woollcott and S.S. Van Dine will be familiar with Sir John Hall's work. And as it has been solemnly asserted, in print, that the names of both Mr. Woollcott and Mr. Van Dine are but pseudonyms of the writer of this piece, the circle is very much narrowed. So I feel moderately safe in going ahead, especially as I have unearthed one or two details on my own account.
Towards noon of a day in July, in that far-off year, Mr. Clay, the manager of the Catalonian Cork-Cutting Company, was in the rear of his premises in Northumberland Street, London. He heard two pistol shots from within the house, one shot following the other at a five-minute interval. He paid no attention, since he knew that one of the residents of the house had, for a month past, anticipated Sherlock Holmes in the eccentric custom of indoor pistol-practice.
After a few minutes, a rear window on the second floor was opened, and there appeared the hero of the story. His conduct, his accoutrement, and some of his speeches, have always recalled to me those half-demented and curious persons who flit through the novels of Mr. G.K. Chesterton. He was a man in his forties; wearing, I think, side-whiskers, and carrying in one hand an umbrella, in the other, half a pair of tongs. He put one foot on the sill, and seemed about to jump twenty feet or more into the yard.
This horrified the Catalonian cork-cutter, not only because the stranger's face was covered with blood, but because of the flagstones and an area, with iron railings, directly below the window. He adjured the bearer of the umbrella, in the name of God, to do nothing desperate, but to tell him what was the matter.
'Murder is the matter!' replied the gory one, and continued his preparations for a desperate leap.
Mr. Clay sent one of his employees for the police, and ran indoors to try to get into the second-floor apartment. While he was banging at the locked doors, he heard glass breaking, and on looking out again, found that the mysterious person had jumped into the yard; fought off a workman who tried to stop him; clambered over a high wall into the next yard — still armed with the umbrella; gained an alley between the houses; and made his way into the street.
Here, he was surrounded by a group of people who had come running from various directions. He complained that someone who lived at Number 16 had tried to murder him. One of the men in the street must have secured the umbrella — perhaps while the wounded man was adjusting his cravat, or brushing off his clothes — for the stranger asked for the umbrella again, and said that he must be getting to his office. This in spite of the fact that he had lost his hat; had a terrible wound in the back of the neck; another, which was bleeding freely, on his cheek; and that both his hair and whiskers were singed.
Duty was evidently the keynote of his character. He was an officer and a gentleman, and to introduce him by name, he was Major William Murray, late of the 10th Hussars, but a total stranger to all in the street. As it will appear presently, deception was in his eyes a far more grievous offence than personal violence, and to him unsportsmanlike conduct seemed the blackest of sins. A man in the crowd reasoned with him about going to his office.
'You are badly wounded,' said this one.
'Am I?' replied the Major.
'Indeed, you are fearfully wounded.'
Then the Major remarked:
'It's that damned fellow upstairs — Grey.'
'There is nobody named Grey in that house,' the man returned. 'But if you mean the man I saw you go in with, about half an hour ago, his name is Roberts.'
Then, at last, the Major allowed a faint note of bitterness to creep into his tone.
'He told me,' he said, 'he told me, that his name was Grey.'
Meanwhile, much was going on in and about Number 16 Northumberland Street. The occupants of that and nearby houses had all heard the pistol shots, and one of them had heard other noises — as if someone were beating a mattress. But no one gave much thought to the reports, since they all knew the habit of their neighbour, Mr. Roberts, of amusing himself by target practice. Roberts was, by profession, a solicitor; actually he accommodated people by lending money. This he did at no great disadvantage to himself — his idea of a proper rate of interest being 133 ⅓ per cent, per annum.
Inside the house, during the talk on the street, was a Mr. Preston-Lumb, an engineer. To him came young Mr. Roberts, son of the moneylender.
'Oh! Mr. Lumb,' he cried — forgetting, in his excitement, the glories of the hyphenated name, 'oh, Mr. Lumb, someone has been and murdered Father!'
Thus, at last, we learn the real origin of the remark which Miss Lizzie Borden called up the stairs to Bridget Sullivan, on another warm and sanguinary noonday, many years afterwards.
Meanwhile, the man in the crowd, and most of the crowd, too, were escorting the wounded Major, first to a chemist's for immediate relief, and then to a bed in the Charing Cross Hospital. His injuries were serious, but he was able, as they walked along, to give the First Citizen a perfectly lucid account of the surprise attack which had been made upon him by the fellow who said his name was Grey.
When the police arrived, and began to search for Mr. Roberts, another inquirer came upon the scene. This was one Timms, a man who had been engaged in washing down the back of the house. To him, shortly before the shots were fired, had come Mr. Roberts, given him a shilling, and asked him to go to the top of St. Martin's Lane, and buy a linnet. He added that the price of the bird was ninepence. Now, Mr. Timms returned, and was left in possession of the linnet, and of the threepence change.
This, in a modern American murder trial, would have been a winsome incident, to be repeated to the jury by the weeping lawyer for the defence, coupled with a demand for the instant acquittal of the prisoner, as one whose tender heart was solely concerned with feathered songsters of the air.
The police, by means of ladders, at last effected an entrance to the rooms of Mr. Roberts. To these locked apartments hardly anyone, not even the moneylender's son, had ordinarily been admitted.
The officers looked at an amazing sight. The rooms were elaborately overfurnished in the French style of the period of Louis Philippe. There were half a dozen good watercolour paintings, with heavy gold frames. Brackets and shelves were ornamented with statuettes and bric-a-brac under glass covers. The floor space was crowded with ormolu tables and boule cabinets. Everything in the room was filthy with dirt and dust — the thick, black encrustation which follows years of neglect. On the floor was a great heap of crumpled papers, also powdered with dust, while the marble mantelpiece was scarred and chipped by the bullets from Mr. Robert's pistol.
In the front room the ornate and dirty furniture was little disarranged, but the other room showed the marks of a terrific fight. Chairs and gilded tables had been upset. The dust had been beaten down; the inlaid cabinets were smeared by bloody fingers. There were splashes of blood on the walls, and a shower of drops of blood on the glass covers over the ornaments. In places, the room looked 'as if a bloody mop had been trundled round and round'.
The police found parts of the broken tongs, 'actually coated with bits of flesh and blood', and another weapon of the fight, a broken wine bottle, lying in a pool of blood. Near the wall in the front room, his head a shocking mass of wounds, lay the owner of all this: Roberts, the moneylender. He had a dozen or twenty injuries, any one of which looked as if it alone should have been instantly fatal. Yet he lived, and could talk.
He, also, was taken to the hospital, where, to the astonishment of the surgeons, he lived for six days. Most of this time he was conscious, but did not say much to help the police. He said that Murray, whom he met by accident in the street, had come to his rooms for a loan. And then, 'Murray shot himself in the neck, attacked me with the tongs like a demon, and hit me with a glass bottle.'
Aside from the improbability of this, the chief wound of the Major made the moneylender's story absurd, and indicated that Roberts had done the shooting. The Major had said, from the start, that Roberts was an utter stranger, whom he had met in the street; that he had been asked to come to the house in Northumberland Street to discuss a proposed loan to a company, and that he had been shot and almost killed for no reason which he could imagine. He then defended his life with the weapons that came to hand.
Young Roberts was brought to his bedside, but still the name meant nothing.
'What Roberts?' said the Major.
'Why, the son of the Roberts who shot you,' was the reply.
Then the exasperation of Major Murray burst forth again.
'Why, damn him,' he said, 'he ought to be hanged for shooting a man on the ground!'
To the sporting Major, especially at a time of the year when the thoughts of all Englishmen were dwelling upon the approach of the grouse season, it was scandalous that Roberts had not flushed him before firing.
Since Roberts died without giving any reason for the fight, and since it was a mystery to Major Murray, the police continued to search the rooms for an explanation. At last, as in a detective story, they believed they had found it in a few marks on a bloodstained sheet of blotting paper. Holding this to the mirror, they deciphered the name 'Mrs. Murray', and an address: Elm Lodge, Tottenham. There were also some fragments of letters from Mrs. Murray to Mr. Roberts.
The inquest was held ten days after the fight. The jury met in the hospital, where they could most easily inspect the battered remains of the man who lost the combat, and also question the winner of it. The so-called Mrs. Murray appeared, heavily veiled. When she lifted this veil, she disclosed 'the features of a remarkably pretty woman' of about twenty-five. Her name was Anna Maria Moody. Seven or eight years earlier, she had left her family 'to live under Major Murray's protection', and she had called herself Mrs. Murray for five years. The Major had taken Elm Lodge for her, and had always treated her in the most 'noble-hearted manner', in accordance with his disposition, which was 'amiable and kind'. When her baby was born, she was embarrassed for funds, and was unwilling to ask for more money from the Major, who, although apparently a bachelor, was 'under heavy expenses'.
Someone told her of Roberts; she went to him, and found him willing to lend her fifteen pounds, provided she signed a three-months' note for twenty pounds.
She had never been able to pay the debt, but had continued to make quarterly payments of five pounds, as interest. From the beginning, Roberts had tried to make love to her, and offered to release her from the debt, if she would leave Major Murray, and go to Scotland with him.
It was believed that Miss Moody told the truth; that she was faithful to the Major; and that she was forced to accept Roberts's company, and go with him usually chaperoned by his wife to church and to entertainments; and even to write affectionate notes to him; and that all this was the craft of a helpless woman who was badgered and threatened by a usurer. She said the two men had never met before the day of the fight, and Major Murray had not known of the other's existence.
The Major gave his testimony in the hospital ward; his throat bandaged, and his neck too stiff to let him move his head. He unfolded a tale which impressed everybody with its melodramatic qualities and caused Thackeray to refer to the affair in Roundabout Papers .
Roberts had accosted him in the street; introduced himself as 'Grey', and offered a loan of fifty thousand pounds to the Railway Palace Hotel, of which project the Major was a director. The two men went to Roberts's rooms, where the host left his guest alone for a few minutes. (He went on the errand about the linnet, in order to get rid of a possible witness.) He came back, stopped behind the chair in which the Major was sitting, and, under pretence of looking for some papers, held a pistol directly against the neck of his victim, and fired. The Major fell to the floor, paralysed. Roberts left the room again, and came back to see the Major beginning to move. He walked up and again fired at his right temple. The outrush of blood from this wound relieved the Major a little, and, as he said, 'I knew if I could get on my feet I could make a fight for it.'
He opened his eyes and saw the tongs. With these in his hands, he jumped up and attacked his intending murderer. Then occurred a fight which raged all over the room. The tongs were smashed against Roberts's skull, after which the Major found a large black wine-bottle and smashed that in the same manner. Both men were up and down, sprawled on the floor, and fighting desperately for whatever weapon the Major tried to employ. Once, Murray caught up a metal vase and threw it at the other's head but missed. Two or three times, Roberts seemed to be down and out, but he would recover his feet, and — a hideous sight — come lurching towards the Major, who was trying to find an escape from the apartment. At last Roberts fell on his face as though dead; the Major pushed him through into the front room, shut the folding doors, and leaped out the window. He regarded the men in the back yard as possible enemies, because he thought that people who could listen to pistol shots and all the uproar or the fight, and take no notice of it, must be associate ruffians in a den of thieves and murderers.
Major Murray's story was corroborated by all the facts known to the jury, who brought in a verdict of 'justifiable homicide' — this amidst the applause of the crowd of spectators.
Roberts's motive for the attempt at murder seems absurdly inadequate but it is probable that, in his desperate infatuation for Miss Moody, he thought that with the Major out of the way he might somehow become the heir to her affections. How he planned to dispose of the body is not clear: perhaps, in the mass of other rubbish which filled his strange dwelling, he thought that the corpse of a retired officer would pass unnoticed.
Miss Moody, like Mr. Timms's linnet, disappears from the history. Whether she was a member of the Major's family at a later date, I do not know.
If you should be eccentric enough to look at The Times for April 1, 1907, you will find this, under Deaths:
MURRAY, on the 28th March, at Ossemsley Manor, Christchurch, Hants, Major William Murray, late 97th Regiment, and 10th Hussars. Service Newmilton, 9 a.m., Wednesday. Cremation, Woking. No flowers, by his special request.
All the bullets of that damned fellow upstairs had not prevented the gallant Major from reaching the hearty old age of eighty-eight. But not even in the Crimea — if he was in that war, which is doubtful — did he ever come so near death as on that day when he fought 'like a demon' against a man whose name, and whose purpose, were alike, to him, a mystery.


AOP works in addition to, not as a replacement for, object-oriented programming (OOP). AspectJ, a free AOP implementation for Java, helps create software systems that are easier to implement, understand, and maintain.
In Part 1, I introduced basic AOP concepts, while in Part 2 I presented an AspectJ tutorial. Armed with your new AOP and AspectJ knowledge, in this article you'll learn how to modularize crosscutting-concern implementations with real-world examples.
Although I discuss several AspectJ examples, by no means do I imply that such implementations can only work using AspectJ. In general, AOP (and for that matter, any other programming methodology) is not about what but about how. This article's examples demonstrate that implementing software systems with AOP offers crosscutting-concern modularity advantages, including more focused code and maintenance ease.
I keep the examples intentionally simple to focus on AOP's and AspectJ's usages. For example, in the thread-pooling example, I do not implement the pool management's full functionality. However, I do concentrate on how to apply the AOP techniques. Also note, for logging I deliberately use System.out.println() instead of the logging aspect to keep the focus from the main problem to the logging concern.
This article looks at examples from several categories: resource-pool management, policy enforcement, characteristics-based behavior, and flexible access control. I wrap up the article (and the series) by presenting several other ways to use AspectJ in your work.
One common way to optimize resource usage recycles previously created resources such as threads and database connections.
A typical OOP approach to introducing resource pooling requires you to make a few up-front decisions. To wit, the design must specify when and how to obtain resources from the pool and how to put them back. Since profiling the system necessitates many optimizations, designing up-front resource pooling proves difficult. However, introducing such support afterwards requires you to modify many source files. (See Part 1's "Architecture's Dilemma" section for more details.) Further, the conventional approach lacks agility; it is not easy to turn on, off, or tune such optimizations.
Let's see how AOP and AspectJ help implement resource-pool management in a modularized fashion.
Pointcut threadCreation() captures joinpoints, thus creating a new thread object taking a Runnable object as the argument.
Advise the threadCreation() pointcut to first check the thread pool for available threads. If no thread is available, create a new one. In either case, set the delegatee to the Runnable object passed in and return that object instead. Note, you do not call proceed() in this advice, so therefore you never execute the captured operation.
Pointcut session() captures the run() method's execution of any ThreadPool.DelegatingThread objects.
By putting session() inside a while(true) loop, you advise session() to never finish the servicing. That ensures a thread, once created, never dies. Once a request is processed, you put the thread back into thread pool and put the thread into waiting state.
Pointcut threadStart() captures a call to the Thread.start() method. It uses isAlive() to check if the thread previously started. That would happen for a thread obtained from a pool and now in a waiting state. Wake up the thread by notifying it. If the thread had not started yet, as for a freshly created thread, proceed with starting the thread.
Note that you made no changes to UppercaseServer.java. The code for a simple test client is in UppercaseClient.java.
You can use the same technique for pooling database-connection objects. Simply capture joinpoints that create new connections and advise them to use one from a connection pool instead, if an appropriate connection is available. You also need to capture joinpoints that close connection objects and advise them to instead put those objects back in the resource pool.


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Zyra International NET //// Cellphones //// Electrical Shops //// Mobile Phones //// Site Index
Decal Girl
Get yourself some full colour skins for your electronics at Decal Girl. Your gizmos will look different from everyone else's, unless they buy the same one's of course.
Decal Girl:
"It all started with a vision.
A small company that was formed in 2003 by a young couple in Delaware made waves its first year. Focusing on quality, craftsmanship and support, DecalGirl was producing a small line of high-quality, photo quality removable graphics for show vehicles.
Later that year, a dusty original Xbox console sitting on a desk in the company's tiny one-room office led to a revelation. The same high-quality graphics we produced for magazine-featured cars and trucks looked even better on a game console.
No corners were cut, no expense was spared - the best materials, the best print quality, the best equipment were combined to launch an entirely new line of full-color skins for popular game consoles with the highest quality possible.
Within 12 months, the concept had taken hold. Additional platforms were added, more staff was hired and the company continued to garner rave reviews for the products.
What started as a small hobby for two grew over the ensuing years to a streamlined, efficient and dedicated global organization that employs almost two dozen people in a 8,000 sq ft office, showroom and production facility in the same small resort town in Delaware.
Since 2003, DecalGirl has been on the cutting edge of the consumer need to individualize and personalize the ever-growing supply of personal electronic devices.
Covering everything from cell phones and game consoles to E-readers, MP3 players, and more, our skins provide our customers with high quality, full color art that protects their devices from scratches and blemishes while also showing off their unique style".
http://www.decalgirl.com affiliate program is with Commission Junction


Welcome to the Shareshill Bowling Club website. Shareshill Bowling Club runs twice weekly social bowling sessions, and has teams in the Cannock Crown Green and Short Mat leagues.
Shareshill Bowling club or 'Shareshill Indoor Bowlers' as it was known, started in October 2007 with 6 crown green bowlers who were looking for somewhere to play in the winter months. The club has since grown to 50+ members.
The club is mainly year round social bowling, there is no pressure to attend the main principle is to come when you can make it and feel relaxed and enjoy yourself - it is as much a social club as a bowling club.
In addition members can now enjoy more competitive bowling, with the club recently joining the local Crown Green and Cannock Short Mat league. The Crown Green League begins in April and finishes in September, with the Short Mat league being played from October to March. Members now play matches all over the Cannock area throughout the year.


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Карпов — русская фамилия, которая изначально была отчеством от канонического мужского имени Карп ( — плод). По заключению большинства исследователей название вида речных лучепёрых рыб к этой фамилии не имеет никакого отношения. Тем не менее, Б. Унбегаун в своих записках не исключал такую возможность, хотя анализ частотности этой фамилии указывает, что это маловероятно.

Со временем в русскоязычной среде на базе фамилии Карпов появилось огромное количество модификаций и производных форм: Карпеев, Карпиков, Карпичев, Карпочкин, Карпунин, Карпухин, Карпушин, Карпушкин, Карпычев и другие. Среди украинского населения получили также распространение фамилии Карпенко, Карпушенко, Карпович и ряд других.

Среди этих форм Карпычев и Карпуничев являются фамилиями из отчеств второй степени, то есть первый носитель фамилии был внуком обладателя имени Карп или Капруня. В некоторых случаях фамилия Карпов и её производные могла вести своё происхождение от глагола «карпать(ся)», который в некоторых диалектах русского языка имел значение «медленно делать что-либо», «копаться», а в говорах Белоруссии слово «карпач» означало «ленивый работник».

Примечания

Русские фамилии
Фамилии по алфавиту


If you've been to Smith's since the first of the month (February 2018), you may have noticed it looks slightly different on the inside. There is no longer a Post Office at that location.
The post office boxes have been moved to the main branch. Although the physical post office boxes have moved, according to Post Master Derek Sharpe, there will be no changes to box numbers or addresses.
Smith's will continue to sell postage stamps in their Money Services Department.


My biopsy showed hurthle cells. My questions is whether the normal thyroid has hurthle cells? I am somewhat confused by what I have read. Does the mere presence of hurthle cells mean something? I really couldn't find anything in my research. When I got my path report and my endo sent me on to a surgeon and thyroid cancer specialist I didn't question about the path report. I just proceeded to the thyroid cancer specialist who said it was up to me whether I wanted to go to surgery then or wait and watch. Also I consulted with a surgeon who was adamant about just a partial so we focussed on why she didn't want to do a TT. I decided to go to Mayo in Jan. to meet with a top endo and have surgery there if warranted.
Now I am wondering about hurthle cells. Can anyone tell me if everyone has hurthle cells in thyroid?
I believe Reece has said if encapsulated that is where the trouble lies.
Hurthle cells in the FNA usually always call for removal of the thyroid, or at least 1/2 of it. Hurthle cells are suspicious, and there is no way to tell if they are cancerous until the thyroid is taken up and sliced up under scrutiny and close examination. I had hurtle cells in my thyroid, had 1/2 out. when they biopsied it on the slab, they said it was benign......a good thing, but it still needed to come out. I'd err on the side of caution, get it out.
I've replied to your other post re; my situation: I too, have "hurthle cells" from my biopsy. Three endo's agreed I don't need surgery. I've questioned them endlessly after much research. They sd they've had patients with hurthle cells that are big red flags and do need surgery, mine are typical of Hashimotos'. I sd "then why don't all hashi people get them?", no good reason. From what I've read the number of hurthle cells more than 75%, nuclei, displasia etc are "flags", atypia etc Mine were metaplasia with clusters of reactive follicular cells. They took 7 smears and no maligant cells.
Here's what I have found out. The two main types of thyroid tissue are follicular cells & parathyroid or something like that. Hurthle cells are a type of follicular cell.
It seems when it starts growing & invading then it becomes a cancerous hurthle cell. My youngest daughter had follicular cells in her biopsy which was considered benign by the pathologic.
So, where does that leave those of us who have had hurthle cells found in a FNA?? I do not know. In January I see another thyroid cancer expert ( an endo) and will let you folks know what I find out.
MG-----If you see this could you offer your 2 cents?
Last edited by osteoblast; 11-25-2008 at 06:22 PM.


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Non-Invasive Prenatal Paternity Test
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Targeted Sequencing Panel 22 – TSP22™
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BRCA1 & BRCA2
Tumour Mutational Burden
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Circulating Cell-free tumour DNA (cfDNA)
Oncomine Comprehensive Targeted Sequencing of DNA and RNA in Cancer
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Can the DNA Test Help You Solve An Unanswered Question In Your Life?
It is safe to say that in recent years, the DNA test has changed the way we can relate to and perceive our world. With so many advances in the technology of DNA testing, the utilization of these tests has become very commonplace. This has made it possible for the average person to now get answers to many questions that were never before obtainable. This, of course, has created a peace of mind that was never before even considered possible.
Although there are many reasons for considering DNA testing there is some very beneficial ways in which to use the test which is certainly worthy of discussion. Some of those uses are discussed below:
There are many people who seem to no longer be able to sustain a monogamous relationship. Those persons faced with the possibility of a cheating partner know the stress and anxiety tied to such a traumatic, emotional experience. Consequently, the DNA test has been a blessing in assisting these suspecting partners in discovering information that can provide substantial answers to many of the questions regarding the potential infidelity.
By providing the lab with samples of such articles as underwear, bed sheets, and condoms, quite often it can be determined whether or not the material is male or female and whether the samples match the alleged cheater. Therefore, enough information can be obtained to put the suspecting partner on the right track to making a determination as to what their next course of action should be.
Ancestral lines are also common usages for considering DNA. Many people are now fascinated with their family tree and are spending hours researching this information to compile the necessary data for having conclusive information regarding this. The DNA testing can assist in determining true ancestral connections and completion of the family lineage. If interested in an ancestry DNA test click here.
Life on other planets has been a mystery to all of us for years. Some people have believed in such all along while others have scoffed at such an absurd idea. But now, as scientists begin to study life sources from other galaxies we are able to gather scientific evidence which will substantiate the truth of this one way or the other through the utilization of the DNA test.
Paternity testing has long been a use DNA and is on the rise as we experience more and more questions in this area. It is important for both the mother and the father to be able to ascertain whom the father truly is in many cases and DNA has provided conclusive evidence in doing so. It has also provided answers to adult children who have long questioned who their "real" parents might be. The peace of mind achieved with such testing is truly priceless for those involved. Results are also extremely accurate providing a 99.99% probability of paternity. More information about this test can be found by visiting this webpage.
As accredited DNA laboratories continue to develop more specialized uses for the DNA test, the popularity of these tests will also continue to increase. The advancement of science, although sometimes controversial, can be said to provide the much needed answers for many persons who have struggled with unsolvable dilemmas for many centuries in the past.
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We are monitoring the ongoing Coronavirus (COVID-19) pandemic closely and are complying with the Government's guidance for the workplace.
Our offices are still open, and we are processing samples and fulfilling orders. To keep you safe we are washing and sanitising our hands before packing orders and they are then placed in our daily mailing services. Unfortunately we cannot allow drop-ins at our office until further notice and all sample collection appointments have been postponed.
The laboratories are still open, are adhering to local guidelines and are processing samples as usual. If delays due to social distancing measures are likely to affect your results due date, then we will inform you immediately.
We are experiencing some delays with all postal and courier deliveries. If you have posted samples back to us but have not received notification that they have been received please track them and check your junk or spam folder before contacting us to request an update.
Please quote your case reference number when contacting us to enable us to respond more quickly.
All results are still being issued on time and you will be contacted if we anticipate any delay with your case.


Hayden Hillegass scored an unassisted goal with 15 minutes to play to give host Faith Lutheran a 1-0 boys soccer win over Legacy on Wednesday.
Goalkeeper Landon Amick made five saves to get the shutout.
Palo Verde 3, Centennial 1 — At Palo Verde, Michael Vogel had a goal and an assist to help the Panthers hold off the Bulldogs.
Cole Wener and Tyler Olenak each added a goal for Palo Verde.
Armando Gutierrez scored Centennial's goal.
Las Vegas 5, Desert Pines 1 — At Desert Pines, Sergio Aguayo scored four goals to power the Wildcats past the Jaguars.
Luis Hernandez added a goal, and Nathan Zamora and Manuel Alfaro each notched two assists for Las Vegas, which led 2-0 at halftime.
Joel Sanchez scored on an assist from Benjamin Diaz-Ramirez for Desert Pines.
Foothill 4, Equipo Academy 0 — At Foothill. William Potter made five saves in the Falcons' shutout of the Yeti.
Devan Henriott, Ryder Cook, Zachary Sines and Ludvig Hansen each scored for the Falcons.
Foothill's Colton Cook added two assists.
Cimarron-Memorial 6, Rancho 1 — At Cimarron, Fernando Arevalo notched three goals and an assist, and Jimi Villasenor chipped in with two goals and an assist as the Spartans routed the Rams.
Diego Zacarias supplied a goal and an assist, and George Balcazar, Diego Juarez, and Shayr Garcia-Reyes each added an assist for Cimarron, which led 2-0 at halftime.
Jesus Leon scored on an assist from Alexis Bravo for Rancho.
Bonanza 7, Shadow Ridge 1 — At Bonanza, Efrain Mayorga supplied three goals and two assists to lead the Bengals to a rout of the Mustangs.
Jonas Bryant and Luis Antonio each had two goals for Bonanza, which got an assist from call-up Guillermo Mungia.
Isaac Arcila scored Shadow Ridge's lone goal.
Eldorado 8, Cheyenne 0 — At Eldorado, Vicor Moran had three goals and an assist to help the Sundevils defeat the Desert Shields.
Roberton Gonzalez added two goals and three assists, and Francisco Ulloa-Tapia, Luis Gutierrez and Erk Llamas each scored once for Eldorado.
Leonel Sedano had two assists, and Emiliano Garcia made two saves to get the shutout for the Sundevils.
Pahrump Valley 9, Adelson School 1 — At Pahrump, Fernando Martinez-Fontana scored twice to lead the Trojans over the Lions.
Christian Gonzalez, Alvaro Garcia and Abraham Alvarez each added a goal and an assist, and Vincent DiBlasi, Christopher Vega, Rafael Nunez and Christian Mott each scored once for Pahrump.
Jose chavez added two assists for the Trojans.
Micah DeLeon had Adelson School's goal.
Boulder City 3, SLAM Academy 1 — At SLAM Academy, the Eagles scored twice in the first half and defeated the Bulls.


Unusual is a simple application for funds impressive display .
Note - Tablet users please do not use this , as all wallpapers are portrait mode and do not fit well for tablets.
+ high wallpapers detailed 2160 X 3840 pixels.
+ wallpapers are All portrait, landscape for users and tablet users sorry.


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Helena Bargholtz (born 1942 in Lidingö, Stockholm County) is a Swedish Liberal People's Party politician. She was a member of the Riksdag from 1998 to 2006, and from 2009 onwards, although she threatened to leave her party over the controversy of the prostitution laws started by fellow Liberal MP Camilla Lindberg.

External links
Helena Bargholtz at the Riksdag website

1942 births
Living people
People from Lidingö Municipality
Members of the Riksdag from the Liberals (Sweden)
Women members of the Riksdag
Members of the Riksdag 1998–2002
Members of the Riksdag 2002–2006
Members of the Riksdag 2006–2010
20th-century Swedish women politicians
20th-century Swedish politicians
21st-century Swedish women politicians


Factual error: When Bourne is tapping into the phone of the American consulate investigator, the display of his Siemens cell phone shows Pamela Landy's phone number as an incoming call, giving him the option to reply or reject the call. But at this point, they have already been talking for a while.
Factual error: When Bourne drives from Naples to Berlin, he wakes up from a nightmare at Dreilinden, just outside of Berlin (easily recognizable by the bridge in the background). A few scenes later he is seen driving through an Alpine landscape which he should already have passed long before getting to Germany.
Factual error: The sirens used in Munich and Berlin are not German sirens, the ones in Munich sound like from another European country and at the demonstration in Berlin an American siren can be heard.


Paper Grain: The direction most of the fibers within paper generally lie, corresponding to the direction of their flow on the papermaking machine.
Paper Opacity: Nontransparent property which prevents or reduces "show through" of printing from the book side of the next sheet.
Via digital watermark consider adding monograms, coats of arms, or book subject/part wallpaper designs to some, or all pages.
Too much of a good thing: While technology exists to jam pack content on a page, and layer it with digital watermarks, don't use it in such a way that it splits the reader's attention too much. You don't want readers feeling like they have a puzzle book that is hard to read.
Looking for other ways to have your manuscript "at hand"? A tablet may be a better compromise between a desk or laptop and a phone. Again, Android users can download MS Word app for free, while Windows users can access MS Word for free, while online. Many of today's tablets can also attach keyboards, mice and wireless printers with ease while having robust memory (both speed and capacity).
FREE: Submit a copy of your manuscript in MS Word and we'll convert it to PDF at no charge. Electronic approval is required before using converted PDF for print production. These electronic book files are meant for personal and family use and enjoyment, as they will contain no Copyright or Digital Rights Management (DRM) protections.
OR EPUB file (more "traditional" EBook format) of interest? Basic file conversion is free, but seldom does a basic conversion result in a file authors are happy with due to the differences between the printed page and EBook formatting. If further services are desired, they can be billed at only $10.00 hour – over 50% savings.
Electronic file offers may be combined and files provided via Dropbox, Google Drive, or Box.com free of charge. Mailed file services available for a fee.
Send your manuscript (with production instructions and discount code), mailing information, and deposit to arrive at the publisher postmarked no later than 11-25-16 with code.
Use this Discount Code ONLY: "ENov16Conv".
Do you like adopting new bells and whistles for your computer? Have you checked out this database of cool (and helpful) stuff?
Special Postcard Design Note: Be careful in adding your name/address to a postcard design. As both sides of the mailpiece are fully viewable and the only notice of which side is "up" is postage, do not place your name and address in a standard addressing format (3 lines roughly center of card) on either side of the card – unless you want the card returned to you. Because of the nature of mailed cards and automated sorting systems, cards may get "flipped" in the mail stream and returned to you: this acts as a return service, effectively "using" the postage to mail the card to yourself.
Use of variable data printing can further customize or personalize title pages. i. e. "Carolyn's history of Crowder", providing space on the page for the owners surnames included in the book or immediate family index listing, etc.
Highlight content within your book, or add photographs not included in the manuscript.
If color binding, this may be a value-added way to include some color photographs that were discarded or "downgraded" to black and white in the interior of the book.
The best font ideas will not work for your book, if you don't send files with the appropriate font information to the printer. Click here for information on how to embed (or substitute) fonts in PDF from Adobe.
New to building web pages and email stationary? Be careful with using symbols. If the person on the other end doesn't have the font your symbol is in, it will substitute characters and may make your page look strange. While symbols are faster to load than graphics, perhaps a diamond, scroll, etc. would be a good design idea.
While actual fact is not copyrightable, everything in a book that supports facts are. Because of this, if a new book of genealogy is produced, it is able to state that Uncle Harry was born on his birthday, whether that fact was previously published in copyrighted work or not. As long as the author has done their own research and arrive at the same fact, it may be used.
Adding photocopies of someone else's data forms.
Transcribing facts from a book without permission or research.
Take our expanding family of publishing packages as a good starting point, or use them as is! The newest package available is our Soft Cover Mini-Mailer. It covers 8.5×11″ books and smaller of no more than 200 pages, digital manuscript preparation, soft cover graphic art design, publishing, 50 mailing boxes (or 100 priority mail boxes with $30.00 credit), promotional flyers and more. Visit the package page for more details.


Before you go ahead and decide to keep animals in a residential area, you need to consider the impact these animals have on your neighbours. Some of the animals, as well as birds, might not be suitable for residential areas, due to the odour or noise that they produce or the kind of vermin that they attract.
If your pets end up causing a disturbance for the neighbours, you might be slapped with complaints that might end up compromising the safety of the animals.
Let us look at the general guidelines to follow to keep animals in the residential area. However, these guidelines vary from one locality to the next.
Make sure you choose animals that don't produce too much noise to disturb the neighbours. Additionally, choose animals that aren't so big for the available space.
The animals you choose shouldn't prove to be a threat to the neighbours. Animals that knockdown objects or destroy vegetation aren't the perfect choice for towns.
Additionally, animals that chase kids around aren't the perfect choice; this is because they might end up causing a lot of accidents that you might not want to be a part of.
When you get the right animals to keep, you need to keep the houses that the animals live in clean at all times. The odour might not be the best thing for your home, as well as the neighbours. With a lot of odours, you will soon be visited by health inspectors.
Additionally, you know that when the place is dirty, the possibility of the animal getting ill is high. Make sure you dispose of the animal waste the right way, and also take time to find a proper way to dispose of animal remains.
You also need to contain the animals on your property. This prevents fouling and damage to other people's property. Remember that straying animals can be impounded, which can result in a fine. If you don't go and claim the animal, it might be killed or sold off. Check out these helpful resources to get the right information to stay on the right side of the law.
You can keep animals in a confined area of your home in a residential place, but you need to understand the rules that govern the keeping of animals in the area. If you don't take great care of these animals, then you risk having them impounded, and you also risk paying a lot of money on the same.


Los Angeles released the last 20,000 "shade balls" into the Los Angeles Reservoir, marking completion of a $34.5 million initiative to protect water quality and to save 300 million gallons of water a year from evaporation. The Los Angeles Department of Water and Power (LADWP)is the first utility company to use this technology for water quality protect—the largest in-basin facility of its kind owned and managed by LADWP.
The small, black plastic balls protect water quality by deterring birds and other wildlife, and protecting water from rain and wind-blown dust. They also help to prevent troubling sunlight-triggered chemical reactions: the reservoirs contain bromide, which occurs naturally in groundwater, as well as chlorine, which was being added to disinfect drinking water. When bromide and chlorine react with sunlight, they form bromate, a suspected human carcinogen.
Dr. Brian White, a now-retired LADWP biologist, was the first person to think of using shade balls for water quality. The idea came to him when he learned about the application of "bird balls" in ponds along airfield runways. The innovative, in-house solution has been used in LADWP's open-air reservoirs since 2008 to block sunlight, prevent chemical reactions and curtail algae blooms. Currently in place at Upper Stone, Elysian and Ivanhoe reservoirs, the shade balls come with the added benefit of reducing evaporation off the reservoir surfaces by 85-90%.
"In the midst of California's historic drought, it takes bold ingenuity to maximize my goals for water conservation," said Mayor Eric Garcetti. "This effort by LADWP is emblematic of the kind of the creative thinking we need to meet those challenges. Together, we've led the charge to cut our city's water usage by 13%, and today we complete an infrastructure investment that saves our ratepayers millions and protects a vital source of drinking water for years to come."
The four-inch plastic balls are made of high-density polyethylene and include UV stabilizer and carbon black color provided by Techmer PM (Clinton, TN), a leading producer of value-added colors and additives for the plastics and fiber industries. Techmer recently partnered with Artisan Screen Printing, an Azusa, California-based blow molder to develop shade balls. Of the 96 million shade balls used on the project, more than 89 million balls were produced by Artisan Screen Printing and include Techmer PM materials.
According to a press release from the LADWP, shade balls not only cut back on the need to chemically treat the water to prevent natural occurrences like algae, they are also an extremely a cost-effective way to reduce evaporation each year by nearly 300 million gallons, "enough to provide drinking water for 8,100 people for a full year," in the words of Councilmember Mitchell Englander.


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Carina Håkansson: Family Care Foundation
Kermit Cole
Carina Håkansson, co-founder of the Family Care Foundation in Sweden, discusses her work with family care homes, psychotherapy and family therapy absent from psychiatric diagnoses and manuals.
From April 25-27, The Family Care Foundation is hosting an international conference entitled "Presence and Participation: Arguments for the Humanistic and Sustainable Work We Do" in Gothenburg, Sweden. The conference aims to counter the arguments for the increasingly manualized practices in caretaking professions, by raising issues around sustainability and research associated with humanism. Stay tuned to MadinAmerica.com in the coming days for information about Live Streaming Video of select conference presentations from Gothenburg.
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Kermit Cole, MFT, founding editor of Mad in America, works in Santa Fe, New Mexico as a couples and family therapist. Inspired by Open Dialogue, he works as part of a team and consults with couples and families that have members identified as patients. His work in residential treatment — largely with severely traumatized and/or "psychotic" clients — led to an appreciation of the power and beauty of systemic philosophy and practice, as the alternative to the prevailing focus on individual pathology. A former film-maker, he has undergraduate and master's degrees in psychology from Harvard University, as well as an MFT degree from the Council for Relationships in Philadelphia. He is a doctoral candidate with the Taos Institute and the Free University of Brussels. You can reach him at [email protected]
Announcing an International Symposium and Institute on Psychiatric Drug Risks and Withdrawal
"Knowing Together" vs. "Knowing Apart": The Importance of Extending Our Network
Finding Human Life on Earth
John Hoggett April 23, 2013 at 8:50 am
A lovely video of a great woman talking so much sense
Lauren Spiro April 30, 2013 at 4:14 am
Thank you Carina Håkansson & Family Care Foundation. I feel that I can now breath a little deeper. Love and using our innate intelligence can and does bring healing from states of extreme emotional distress. I am happy to throw the psychiatric labels I was given into the fire.
Dorothy Dundas April 23, 2013 at 10:33 am
Oh, my goodness! This is so moving and beautiful that it makes me weep for all of my friends who have died as a result of their abusive care in the mental health system in the USA. This dear woman and her whole way of thinking about schizophrenia and all diagnoses would certainly have given me hope when I was locked up back in 1960 in Massachusetts, USA.
This interview is a breath of long-needed fresh air. Hopefully, we can learn from her and those in her community to bring this compassionate outlook to our country and all over the world.
Thank you for a beautiful interview.
Kermit Cole April 23, 2013 at 3:17 pm
This is a small part of a very beautiful interview that will be up soon.
Dorothy Dundas April 23, 2013 at 4:11 pm
Thanks for letting me know, Kermit. She is inspirational. Hope your flight was peaceful.
Stephen Gilbert May 7, 2013 at 8:47 am
Good Grief! The people who work in the Family Care Foundation actually work to help people! Unlike most psychiatrists in this country who only want to pop pills into people and send them on their way! And of course, their issues which are causing them distress never get talked about or worked through.
John Hoggett June 4, 2014 at 3:53 pm
So who knows The Invisible Child, a short story in Tales from Moomin Valley by Tove Jansonn?
It is a story of a child so disturbed she has become invisible and silent. She is taken to live with the Moomin Family. Moomin Mama gives her a secret medicine from Granny and she becomes visible and finds her voice.
An early version of family care perhaps?
https://www.youtube.com/watch?v=B_913bOdfMo
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