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Number: 0871
Aetna considers allogeneic hematopoietic cell transplantation (HCT) medically necessary for the treatment of the following inherited metabolic disorders:
Aetna considers hematopoietic cell transplantation (autologous, allogeneic or cord blood) medically necessary for the treatment of children with infantile malignant osteopetrosis confirmed by bone biopsy and radiographic imaging and when they do not exhibit irreversible neurologic impairment and multi-organ failure.
Aetna considers autologous HCT experimental and investigational for the treatment of mucopolysaccharoidosis or childhood-onset adrenoleukodystrophy because its effectiveness for these indications has not been established.
See also CPB 0140 Genetic Testing, CPB 0442 - Lysosomal Storage Disorders: Treatments, and CPB 0626 - Hematopoietic Cell Transplantation for Thalassemia Major and Sickle Cell Anemia.Background
Alpha-mannosidosis is a rare lysosomal storage disorder in which deficient alpha-mannosidase activity leads to lysosomal accumulation of mannose-rich oligosaccharides. Alpha-mannosidosis is characterized by mental retardation, skeletal changes, hearing impairment, and recurrent infections. HCT increases levels of alpha-mannosidosis, resulting in improvements in neurocognitive and sensorineural function as well as skeletal malformations (Yeskilipek, 2012).
Mynarek et al (2012) reported on the results of a retrospective multi-institutional analysis of 17 patients who underwent HCT. Median age at diagnosis was 2.5 years. After a median follow-up of 5.5 years 15 patients remained alive, 2 having died within the first 5 months after HCT. The investigators reported that t3 patients required re-transplantation due to graft failure. Following HCT, patients made developmental progress, although normal development was not achieved, including an improvement in hearing ability in some but not all patients.
Childhood-Onset Adrenoleukodystrophy
Adrenoleukodystrophy (ALD), an X-linked disorder which more severely affects males, is caused by a defect in the metabolism of long-chain fatty acids resulting in demyelination, neurological deterioration, and death. The majority of patients with ALD suffer from adrenal insufficiency, the neurological symptoms can appear either in childhood or adulthood. Childhood ALD, which is the most severe form of this disease, results in onset of neurological symptoms between ages 4 and 10. These symptoms include visual loss, hearing loss, learning disabilities, seizures, speech impairment, dysphagia, increased pigmentation of the skin, challenges in ambulation, abnormal withdrawal or aggression, poor memory and school performance, fatigue, and progressive dementia (NINDS, 2013).
Shapiro et al (2000) examined if bone marrow transplantation (BMT) can stop the progressive demyelination and neurodegeneration of patients with childhood-onset cerebral X-linked ALD (CCALD). A total of 12 patients were followed for 5 to 10 years after BMT. Electrophysiological, neurological, and neuropsychological studies, magnetic resonance imaging (MRI), as well as plasma very-long-chain fatty acid (VLCFA) measurements were used to evaluate the effect of BMT. Magnetic resonance imaging showed improvement in 1.patient and complete reversal of abnormalities in 2 patients. One patient showed no change from baseline to last follow-up. All 8 patients who showed an initial period of continued demyelination stabilized and remained unchanged thereafter. In 10 patients, motor function remained normal or improved after BMT. Verbal intelligence remained within the normal range for 11 patients; performance (non-verbal) abilities were improved or were stable in 7 patients. Decline in performance abilities followed by stability occurred in 5 patients. Plasma VLCFA concentrations decreased by 55 % and remained slightly above the upper limits of normal. The authors noted that 5- to 10-year follow-up of 12 patients with CCALD showed the long-term beneficial effect of BMT when the procedure is done at an early stage of the disease.
Beam et al (2007) evaluated outcomes of unrelated donor umbilical cord blood (UCB) transplantation after chemotherapy-based myeloablative conditioning and retrospectively determined if baseline studies correlated and helped to predict outcome. A total of 12 boys with X-linked ALD who lacked human leukocyte antigen (HLA)-matched related donors were studied. Baseline studies of neuroimaging, neurophysiological, as well as neurodevelopmental status were performed and patients were subsequently evaluated for engraftment, graft-versus-host disease (GVHD), neurodevelopmental outcomes, and survival. A substudy evaluated whether baseline neuroimaging and neurophysiological studies correlated with cognitive and motor function and if these studies were predictive of post-transplantation outcomes. The UCB grafts had normal levels of VLCFA. Three patients had grade II to IV acute GVHD; 2 had extensive chronic GVHD. Cumulative incidence of overall survival of the group at 6 months was 66.7 % (95 % confidence interval [CI]: 39.9 % to 93.3 %). Median follow-up was 3.3 years (range of 12 days to 6.3 years). As previously reported with BMT, symptomatic patients faired poorly with lower survival and rapid deterioration of neurological function. This study included 3 patients transplanted at a very young age (2.6 to 3.5 years) before the onset of clinical symptoms who continue to develop at a normal rate for 3 to 5 years post-transplant. Although baseline Loes scores correlated with cognitive and motor outcome, neurophysiological studies failed to show statistically significant differences. The authors concluded that transplantation of boys with X-linked ALD using partial HLA-matched UCB yielded similar results to those previously reported after BMT. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation.
Mahmood and colleagues (2007) analyzed survival of CCALD patients who had not received HCT; and (ii) in a subgroup with early cerebral disease, compared survival in those who underwent HCT with those who did not. Retrospective survival analyses were done on 283 CCALD patients who had not received HCT, focusing on a 30-member early stage cerebral subgroup whose neurological disability and MRI severity scores matched those of a 19-member transplanted subgroup previously reported. A Kaplan-Meier survival curve and log-rank test were used for survival analysis and for estimating the difference between the survival probabilities of the groups with statistical significance set at p = 0.05. Mean age at onset of symptoms in the 283 non-transplanted group was 7 years (standard deviation [SD] = 2 years). A total of 131 (SD = 46 %) patients died during the mean follow-up period of 5.9 years (SD = 5.3) at a mean age of 12.3 years (SD = 4.9). The 5-year survival was 66 %; the 5-year survival probability of 54 % in the early stage group was significantly poorer (chi(2) = 7.47, p = 0.006) than the 5-year survival of 95 % in the transplanted group with early stage cerebral disease. The authors concluded that HCT done in the early and progressive stages of CCALD is beneficial, and these findings supported the recommendation that transplantation be offered to patients in the early stages of CCALD.
Miller et al (2011) presented findings on 60 boys who had undergone hematopoietic stem cell transplantation (HSCT) with varying conditioning regimens and allograft sources for cerebral ALD between 2000 and 2009. The median age at time of HSCT was 8.7 years with 50% demonstrating a Loes radiographic severity score ≥ 19 and 62% showing clinical evidence of neurologic dysfunction. Survival at a median 3.7 years after HSCT was 78% (n=47). Five year survival estimates for boys with Loes score < 10 at time of HSCT was 89% and for boys with a Loes score ≥ 10 at time of HSCT was 60% (p = .03). Among study participants who had not demonstrated clinical cerebral disease at the time of HSCT, the 5 year survival was 91% and for study participants who had exhibited neurologic dysfunction the 5 year survival was 66% (p = .08). Cumulative mortality incidence 100 days post HSCT was 8%. Thus, the investigators concluded that post-transplantation progression of neurologic dysfunction depended significantly on the pre-HSCT Loes score and clinical neurologic status.
Approximately 100 cases of fucosidosis have been reported worldwide. Fucosidosis is a rare autosomal recessive lysosomal disorder and is caused by mutations in the FUCA1 gene,w hich is key in production of the alpha-L-fucosidase enzyme. Alpha-L-fucosidase is involved in the breakdown of oligosaccharides attached to certain glycolipids and glycoproteins. Absense of alpha-L-fucosidase results in incomplete breakdown of glycolipids and glycoproteins. The incomplete compounds gradually accumulate within various cells, particularly brain cells, but can accumulate throughout the body, causing cell malfunction. Fucosidosis results in intellectual disability that worsens with age, delayed motor skills development, impaired growth, dysostosis multiplex, seizures, spasticity, angiokeratomas, visceromegaly, recurrent respiratory infections, and distinctive or coarse facial features. Individuals with severe disease typically live into late childhood while mildly affected individuals can live until mid-adulthood (Genetics Home Reference, 2008).
Krivit (2004), in a review of the clinical responses and prospectus of new therapies following use of HCT for a number of disorders including fucosidosis report that over 500 patinets with lysosome and peroxisomal metabolic storage diseases due to deficiency of primary enzymes have been treated with HCT since the treatment option became available. Krivit stated that normal enzymatic activity has been robust in these patients along with excellent engraftment rates.
Globoid Cell Leukodystrophy (Krabbe disease)
Globoid cell leukodystrophy is a neurodegenerative diseorder caused by a deficiency of the lysosomal enzyme galactosylceramidase, resulting in an accumulation of imcompletely metabolized galactocerebroside, which is a component of myelin. The resulting galactocerebroside accumulation leads to progressive white matter disease (Pastores, 2009). Duffner et al (2009) stated that although most globoid cell leukodystrohy patients present within the first 6 months of life, some can present into adolescence and adulthood. He further notes that the only available treatment for infants with early infantile disease is HCT, typically using umbilical cord blood. Duffner further reports that globoid cell leukodystrophy patients receiving HCT perform better neurologically than those following the typical fulminant course of early infantile globoid cell leukodystrophy.
Metachromatic Leukodystrophy
Metachromatic leukodystrophy is an autosomal recessive lysosomal disorder due to the deficiency of arylsulfatase A causing impaired degradation of sulfatide, which manifests in affected individuals as progressive demyelination and subsequent debilitating neurological symptoms. HCT has been used to treat metachromatic leukodystrophy utilizing both umbilical cord blood and bone marrow sources (Patil et al, 2013). Biffi et al (2013) reported on 3 patients who received HCT presymptomatically. Following HCT, the patients showed extensie and stable ARSA gene replacement, leading to high enzyme expression throughout hematopoietic lineages and in cerebrospinal fluid. The three patients showed no disease progression 7 to 21 months beyond the predicted age of symptom onset.
Martin et al (2013) reported the longitudinal outcome following umbilical cord blood transplantation in 27 pediatric metachromatic leukodystrophy patients. Seven patients died of infection, regimen-related toxicity, or disease progression. Twenty patients were followed for a median of 5.1 years, and the results showed that patients with motor function symptoms at the time of transplant did not improve after transplantation. The investigators also found that brainstem auditory evoked responses, visual evoked potentials, electroencephalogram, and/or peripheral nerve conduction velocities stabilized or improved in juvenile patients but continued to worsen in most patients with the late-infantile presentation. The investigators concluded that children who were asymptomatic at the time of transplantation benefited most from the procedure, while children with juvenile onset and minimal symptoms showed stabilization or deterioration of motor skills but maintained cognitive skills.
The mucoipidoses (ML) are lysosomal storage diseases. Symptoms of ML can be congenital or begin in early childhood or adolescence; there are four types of ML and symptoms can range from mild to severe. Symptoms of ML I are either present at birth or develop within the first year of life, often presenting with excessive swelling throughout the body noted at birth. These infants are often born with coarse facial features, gum enlargement, macroglossia, liver and spleen enlargement, hypotonia, mental retardation and skeletal malformations. Many patients suffer from failure to thrive and from recurrent respiratory infections. Most infants with ML I die before the age of 1 year (NINDS, 2011).
ML II is a particularly severe form of ML that resembles Hurler syndrome. Abnormal skeletal development, coarse facial features, and restricted joint movement may be present at birth and affected children often fail to grow and develop in the first months of life, with delays in motor skills being more pronounced than delays in cognitive skills. Children with ML II usually have enlargement of certain organs, such as the liver or spleen, or even the heart valves and have recurrent respiratory tract infections; children with ML II eventually develop a clouding on the cornea of their eyes and an underdeveloped trunk. Children with ML II generally die before their seventh year of life, often as a result of congestive heart failure or recurrent respiratory tract infections (NINDS, 2011).
ML III is a milder form and has symptoms which are often not noticed until the child is 3-5 years of age. ML III also results from a deficiency or defect of the enzyme N-acetylglucosamine-1-phosphotransferase but produces less severe symptoms and progresses more slowly, probably because the deficient enzyme retains some of its activity, resulting in a smaller accumulation of carbohydrates, lipids, and proteins in the inclusion bodies. Individuals with ML IV can present with delays in movement development and coordination, clouding of the cornea of the eye, and severely reduced vision. These patients often have an unsteady gait, do not walk independently. and speech is usually severely impaired. More mildly affected ML IV patients can walk and have better speech. Rarely, ML IV patients may even have only an eye abnormality resulting in vision impairment, but remain without mental impairment (NINDS, 2011).
Martin et al (2006) reported results of the Cord Blood Transplantation Study (COBLT), a phase II multicenter study in 69 patients with lysosomal and peroxisomal storage diseases designed to evaluate the use of cord blood in allogeneic transplantation. The study included patients with mucopolysaccharidoses I to III, mucolipidoses (ML) II (n = 36), adrenoleukodystrophy (n = 8), metachromatic leukodystrophy (n = 6), Krabbe disease (n = 16), and Tay-Sachs disease (n = 3) and all patients received the same preparative regimen, graft-versus-host disease (GVHD) prophylaxis, and supportive care. Sixty-nine patients (64% men; 81% white) with a median age of 1.8 years underwent transplantation with a median cell dose of 8.7 x 10(7)/kg and one-year survival was 72% (95% confidence interval, 61%-83%). The cumulative incidence of neutrophil engraftment by day 42 was 78% (95% confidence interval, 67%-87%) at a median of 25 days and grade II to IV acute GVHD occurred in 36% of patients. The investigators concluded that cord blood transplantation should be considered as frontline therapy for young patients with lysosomal and peroxisomal storage diseases.
The mucopolysaccharidoses are a group of inherited metabolic diseases that are caused by the absence or malfunctioning of specific enzymes needed to break down molecules called glycosaminoglycans, which are long chains of sugar carbohydrates in human cells that help build bone, cartilage, tendons, corneas, skin, and connective tissue. Individuals with a mucopolysaccharidosis (MPS) either do not produce enough of one of the 11 enzymes required to break down sugar chains into proteins and simpler molecules or they produce enzymes that do not work properly, resulting in permanent, progressive cellular damage affecting the individual's appearance, physical abilities, organ and system functioning. In most cases, mental development is also affected. An estimated one in every 25,000 babies born in the United States will have some form of the mucopolysaccharidoses. They are autosomal recessive disorders, meaning that only individuals inheriting the defective gene from both parents are affected. (The exception is MPS II, or Hunter syndrome, in which the mother alone passes along the defective gene to a son.) When both people in a couple have the defective gene, each pregnancy carries with it a one in four chance that the child will be affected. The parents and siblings of an affected child may have no sign of the disorder. Unaffected siblings and select relatives of a child with one of the mucopolysaccharidoses may carry the recessive gene and could pass it to their own children (NINDS, 2013). MPS V, which was also referred to as Scheie syndrome, is a designation which is no longer in use (Dekabon et al, 1976).
Noh and Lee (2014) reviewed the classification and pathophysiology of MPS and discussed current therapies and new targeted agents under development. A Medline search through PubMed was performed for relevant articles and treatment guidelines on MPS published in English for years 1970 to September of 2013 inclusive. The references listed in the identified articles, prescribing information of the drugs approved for the treatment of MPS, as well as recent clinical trial information posted on Clinicaltrials.gov website, were reviewed. Until recently, supportive care was the only option available for the management of MPS. In the early 2000s, enzyme replacement therapy (ERT) was approved by the Food and Drug Administration (FDA) for the treatment of MPS I, II and VI. Clinical trials of ERT showed substantial improvements in patients' somatic symptoms; however, no benefit was found in the neurological symptoms because the enzymes do not readily cross the blood-brain barrier (BBB). Hematopoietic stem cell transplantation, another potentially curative treatment, is not routinely advocated in clinical practice due to its high risk profile and lack of evidence for efficacy, except in preserving cognition and prolonging survival in young patients with severe MPS I. In recent years, substrate reduction therapy (SRT) and gene therapy have been rapidly gaining greater recognition as potential therapeutic avenues. The authors concluded that (i) ERT is effective for the treatment of many somatic symptoms, particularly walking ability and respiratory function, and remains the mainstay of MPS treatment, (ii) the usefulness of HSCT has not been established adequately for most MPS, and (iii) although still under investigation, SRT and gene therapy are promising MPS treatments that may prevent the neurodegeneration not affected by ERT.
Mucopolysaccharidoses I (Hurler's Syndrome)
Hurler's syndrome causes progressive deterioration of the central nervous system and death in childhood.
Staba and co-workers (2004) examined the feasibility of using cord blood transplants from unrelated donors and a myeloablative preparative regimen that did not involve total-body irradiation (TBI) in young children with Hurler's syndrome. A total of 20 children with Hurler's syndrome were given conditioning regimens before receiving cod blood transplants from unrelated donors. The children were subsequently evaluated for engraftment, side effects, and effects on disease symptoms. Cord blood donors were discordant for up to 3 of 6 HLA markers. Neutrophil engraftment occurred a median of 24 days after transplantation. Five patients had grade II or grade III acute GVHD; none had extensive chronic GVHD. Seventeen of the 20 children were alive a median of 905 days after transplantation, with complete donor chimerism and normal peripheral blood alpha-L-iduronidase activity (event-free survival rate of 85 %). Transplantation improved neurocognitive performance and decreased somatic features of Hurler's syndrome. The authors concluded that cord blood from unrelated donors appears to be an excellent source of stem cells for transplantation in patients with Hurler's syndrome. Sustained engraftment can be achieved without TBI. They stated that cord blood transplantation favorably altered the natural history of Hurler's syndrome and thus may be important to consider in young children with this form of the disease.
Boelens et al (2007) analyzed data on Hurler's syndrome patients transplanted in Europe to identify the risk factors for graft failure. These investigators compared outcomes of 146 Hurler's syndrome patients transplanted with various conditioning regimens and grafts. Risk factor analysis was performed using logistic regression. "Survival" and "alive and engrafted" rates after first HCT were 85 % and 56 %, respectively. In multi-variable analysis, T-cell depletion (odds ratio [OR] 0.18; 95 % CI: 0.04 to 0.71; p = 0.02) and reduced-intensity conditioning (OR 0.08; 95 % CI: 0.02 to 0.39; p = 0.002) were the risk factors for graft failure. Busulfan targeting protected against graft failure (OR 5.76; 95 % CI: 1.20 to 27.54; p = 0.028). No difference was noted between cell sources used (bone marrow, peripheral blood stem cells, or UCB); however, significantly more patients who received UCB transplants had full-donor chimerism (OR 9.31; 95 % CI: 1.06 to 82.03; p = 0.044). The authors concluded that cord blood increased the likelihood of sustained engraftment associated with normal enzyme levels and could therefore be considered as a preferential cell source in HCT.
Hansen et al (2008) reported transplant outcomes following a reduced intensity, highly immunosuppressive preparative regimen in 7 patients with Hurler's syndrome. A total of 6 patients received grafts from unrelated donors and 1 received a sibling donor graft. The preparative regimen was well-tolerated. All patients had initial donor engraftment at 100 days; 1 patient had delayed loss of donor chimerism. There was no severe acute graft versus host disease. Six of the 7 children survived a median of 1,014 days (726 to 2,222 days) post-transplant. The authors concluded that this reduced intensity preparative regimen has the potential to support engraftment and improve survival and outcome in patients with Hurler's syndrome undergoing HCT.
Sauer et al (2009) stated that allogeneic HSCT can achieve long-term survival in patients with Hurler's syndrome by correcting the enzymatic deficiency. In an attempt to improve long-term engraftment and to reduce regimen-related toxicity (RRT), these investigators used a fludarabine-based TBI-free preparative regimen. A total of 12 children were studied. Median age at HCT was 14 months (range of 4 to 31 months). CD34 positively selected peripheral blood hematopoietic stem cell were used in 10 children with a matched unrelated donor. Two children with a matched sibling donor received non-manipulated bone marrow. Donor lymphocyte infusions were given in 6/12 children for mixed hematopoietic chimerism. At a median follow-up of 29 months (range of 2 to 85 months), all children engrafted and had either stabilized or improved neurological function. In total, 12/12 patients showed donor-derived engraftment with 9/12 having full and 3/12 having mixed hematopoiesis. One developed acute GVHD greater than or equal to grade II; RRT greater than or equal to grade II was observed in 2 patients.
Guidelines from the International Consensus Panel on the Management and Treatment of Mucopolysacchardosis I (Muenzer et al, 2009) stated that when it is successful, HCT using either bone marrow or UCB cells can prevent and/or reverse many but not all of the clinical features of severe MPS I. It must be performed early in the disease course, before developmental deterioration begins.
Mucopolysaccharoidosis II (Hunter Syndrome)
Hunter syndrome, an X-linked, recessive, lysosomal storage disease, is caused by a defect of the iduronate-2-sulfatase gene. It is diagnosed in approximately 1 out of 65,000 to 132,000 births. In the absence of sufficient enzyme activity, glycosaminoglycans (GAG) accumulate in the lysosomes of many tissues and organs; thus contributing to the multi-system (e.g., cardiovascular, musculo-skeletal, nervous, and respiratory systems) progressive pathologies in these patients. Hunter syndrome usually becomes apparent in children 1 to 3 years of age. Symptoms include growth delay, joint stiffness, and coarsening of facial features. In severe cases, patients experience neurological deficits, enlargement of the liver and spleen, cardiac as well as respiratory problems, and death.
Guffon et al (2009) evaluated the effect of bone marrow transplant (BMT) in children with Hunter syndrome. A total of 8 boys (aged 3 and 16 years) received BMT. In 6 cases, the donor was a sibling with identical HLA status, in 1 case the donor was unrelated but HLA-compatible, and in 1 case the donor was unrelated and mis-matched. Successful engraftment was achieved in all patients, with the proportion of donor cells reaching greater than or equal to 95 % 1 month after transplantation in all patients. Patients were followed for 7 to 17 years and all were still alive, except for 1 boy who died at the age of 10 from unrelated causes. Cardiovascular abnormalities stabilized in all patients, hepato-splenomegaly resolved, and joint stiffness improved, perceptual hearing defects remained stable, and transmission hearing defects improved. Only 1 child required subsequent surgery to correct kyphosis. Neuropsychological outcome was variable and appeared to be related to the severity of the syndrome.
Mucopolysaccharidosis III (Sanfilippo Syndrome)
Sanfilippo syndrome (MPS III) causes severe neurological symptoms, including progressive dementia, aggressive behavior, hyperactivity, seizures, some deafness and loss of vision, and an inability to sleep for more than a few hours at a time. MPS III affects children differently, and its progress will be faster in some than in others. Affected children show a marked decline in learning between ages 2 and 6, followed by eventual loss of language skills, and in some children an inability to speak at all. MPS III is also characterized by loss of some or all hearing. Aggressive behavior, hyperactivity, profound dementia, and irregular sleep may make Children, particularly those who retain normal physical strength, may be difficult to manage due to aggressive behavior, hyperactivity, profound dementia, and irregular sleep. As the disease progresses, children become increasingly unsteady on their feet. Most are unable to walk by age 10 with height growth ceasing. Also, thickened skin and mild changes in facial features, bone, and skeletal structures become noticeable with age. Children with MPS III may also experience narrowing of the airway passage in the throat and enlargement of the tonsils and adenoids, making it difficult to eat or swallow, and recurring respiratory infections are common. There are four distinct types of MPS III, due to alteration of a different enzyme for breakdown of the heparin sulfate sugar chain. Although there is little differentiation clinically between the four types, children with type A present with more severe symptoms and progress more quickly. Some individuals with MPS III may live into their teenage years, or even into their twenties or thirties (NINDS, 2013).
Sanfilippo syndrome (MPS III) causes severe neurological symptoms, including progressive dementia, aggressive behavior, hyperactivity, seizures, some deafness and loss of vision, and an inability to sleep for more than a few hours at a time. MPS III affects children differently, and its progress will be faster in some than in others. Affected children show a marked decline in learning between ages 2 and 6, followed by eventual loss of language skills, and in some children an inability to speak at all. MPS III is also charactgerized by loss of some or all hearing. Aggressive behavior, hyperactivity, profound dementia, and irregular sleep may make Children, particularly those who retain normal physical strength, may be difficult to manage due to aggressive behavior, hyperactivity, profound dementia, and irregular sleep. As the disease progresses, children become increasingly unsteady on their feet. Most are unable to walk by age 10 with height growth ceasing. Also, thickened skin and mild changes in facial features, bone, and skeletal structures become noticeable with age. Children with MPS III may also experience narrowing of the airway passage in the throat and enlargement of the tonsils and adenoids, making it difficult to eat or swallow, and recurring respiratory infections are common. There are four distinct types of MPS III, due to alteration of a different enzyme for breakdown of the heparin sulfate sugar chain. Although there is little differentiation clinically between the four types, children with type A present with more severe symptoms and progress more quickly. Some individuals with MPS III may live into their teenage years, or even into their twenties or thirties (NINDS, 2013).
Mucopolysaccharoidosis IV (Morquio Syndrome)
MPS IV, also known as Morquio syndrome, has an estimated occurance of one in every 200,000 births, with an onset between the ages 1 and 3. Neurological complications include spinal nerve and nerve root compression resulting from extreme, progressive skeletal changes, conductive hearing loss, neurosensitive hearing loss, and clouded corneas. If hydrocephalus develops and is not treated intelligence can be adversely affected but is otherwise normal. Physical growth slows and often stops around age 8 with skeletal abnormalities including a bell-shaped chest, a flattening or curvature of the spine, shortened long bones, and dysplasia of the hips, knees, ankles, and wrists. In more severe cases of MPS IV children may not live beyond their twenties or thirties (NINDS, 2013).
Mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome)
MPS VI, Maroteaux-Lamy syndrome, does not affect normal intellectual development but includes many of the physical symptoms found in severe MPS I. MPS VI, which has a variable spectrum of severe symptoms, is caused by the deficient enzyme N-acetylgalactosamine 4-sulfatase,. Neurological complications include pain caused by compressed or traumatized nerves and nerve roots, clouded corneas, deafness, and thickening of the dura. Growth stops suddenly around age 8 and by age 10 children have developed a shortened trunk, crouched stance, and restricted joint movement. Children with MPS VI may also, in severe cases, develop a protruding abdomen and forward-curving spine. These skeletal changes are progressive and limit movement. Most children with MPS VI have some form of heart disease, usually involving valve dysfunction (NINDS, 2013).
Mucopolysaccharidosis VII (Sly Syndrome)
MPS VII, also known as Sly syndrome, is one of the least common forms of the mucopolysaccharidoses, with an estimated occurance of fewer than one in 250,000 births. In its rarest form, MPS VII causes children to be born with hydrops fetalis, in which extreme amounts of fluid are retained in the body, and in these cases survival is usually a few months or less. Most children with MPS VII are less severely affected, but do experience neurological symptoms including mild to moderate mental retardation by age 3, communicating hydrocephalus, nerve entrapment, corneal clouding, and some loss of peripheral and night vision. These children often present with short stature, skeletal irregularities, joint stiffness, and umbilical and/or inguinal hernias, and may experience repeated bouts of pneumonia during their first years of life, and generally live into the teenage or young adult years (NINDS, 2013).
The NINDS "Mucopolysaccharidoses fact sheet" (NINDS, 2013) states that BMT and UCB transplantation are high-risk procedures and are usually performed only after family members receive extensive evaluation and counseling.
Wolman Disease
Wolman disease is a fatal lysosomal storage disease caused by a deficiency in lysosomal enzyme acid lipase. Wolman disease typically presents in early infancy with diarrhea, massive hepatospenomegaly, failure to thrive, and calcification of adrenal glands, with HCT the only therapy reported to prevent hepatic failure and death, which would otherwise occur during the first year of life (Tolar et al, 2009). Three cases of successful treatment with HCT were reported by Yanir et al (2013), but they also reported on two cases of fatality from hepatic complications.
Infantile Malignant Osteopetrosis
Osteopetrosis is a rare genetic disorder and infantile malignant osteopetrosis (IMO), also known as Albers-Schonberg disease/syndrome or marble bone disease, is the worst subtype of this disease; 70 % of patients die in 6 years of life without proper treatment. Hematopoietic stem cell transplantation (HSCT) offers the only chance of cure for IMO (Zhu et al, 2012).
Driessen et al (2003) performed a retrospective analysis of 122 children who had received an allogeneic HSCT for autosomal recessive osteopetrosis between 1980 and 2001. The actuarial probabilities of 5 years disease free survival were 73 % for recipients of a genotype HLA-identical HSCT (n = 40), 43 % for recipients of a phenotype HLA-identical or 1 HLA-antigen mismatch graft from a related donor (n = 21), 40 % for recipients of a graft from a matched unrelated donor (n = 20) and 24 % for patients who received a graft from an HLA-haplotype-mismatch related donor (n = 41). In the latter group, a trend towards improvement was achieved at the end of the study period (17 % before 1994, 45 % after 1994, p = 0.11). Causes of death after HSCT were graft failure and early transplant-related complications. Severe visual impairment was present in 42 % of the children before HSCT. Conservation of vision was better in children transplanted before the age of 3 months. Final height was related to height at the time of HSCT and better preserved in children transplanted early. Most children attended regular school or education for the visually handicapped. The authors concluded that at present, HSCT is the only curative treatment for autosomal recessive osteopetrosis and should be offered as early as possible.
Tsuji et al (2005) stated that the only curative therapy for IMO is HSCT. Because the number of patients is limited, the conditioning regimen and the use of alternative donors for HSCT have been controversial and not established. The authors reported a case of successful cord blood transplantation (CBT) with a non-myeloablative regimen (NMR) for IMO. The patient was a 9-month old girl with IMO. Before this diagnosis, she had received chemotherapy under the tentative diagnosis of juvenile myelomonocytic leukemia. She was on mechanical ventilation with tracheotomy due to the progression of IMO when she underwent CBT with NMR. The conditioning regimen included fludarabine, melphalan, and anti-thymocyte globulin. Cyclosporine A and methylprednisolone were used for prophylaxis for graft-versus-host disease (GVHD). Neutrophil engraftment was achieved on day 26 after HSCT and had been fully maintained up to the present. Although grade 3 GVHD and hepatic veno-occlusive disease (VOD) occurred, both were controllable. The authors noted that although the pre-transplant condition of the patient was somewhat unusual, this was the first reported case of successful CBT with NMR for IMO. Because of the urgent need, CBT can be considered as one of the HSCT sources for IMO, especially in a severe, life-threatening setting.
Corbacioglu et al (2006) noted that IMO is a rare hereditary disorder of osteoclast function, which can be reversed by HSCT. These investigators observed a high incidence of hepatic VOD in transplanted patients and explored the prevention of this complication by using defibrotide (DF) as a prophylaxis. A total of 20 children with IMO were consecutively transplanted in the authors' center between 1996 and 2005; 11 of these patients were transplanted between 1996 and 2001 and experienced an overall incidence of VOD of 63.6 % (7/11). Veno-occlusive disease was severe in 3 patients and 1 patient succumbed to VOD-related multi-organ failure. Owing to this very high incidence of VOD, DF prophylaxis was initiated in 9 patients consecutively transplanted between 2001 and 2005. In this group, only 1 patient (11.1 %) was diagnosed with moderate VOD. The authors reported a very high risk in patients with IMO to develop VOD after transplantation; and prophylactic DF was implemented in their current transplant protocol and reduced the VOD rate significantly in this high-risk population.
Mazzolari et al (2009) reported on the clinical and molecular findings and treatment in 20 consecutive patients (9 females and 11 males) with IMO, diagnosed at a single center in the period of 1991 to 2008. Mean age at diagnosis was 3.9 months, and mean follow-up was 66.75 months. Mutations in ClCN7, TNFRSF11A, OSTM1, and TCIRG1 genes were detected in 1, 1, 3, and 9 patients, respectively. Six patients remain genetically undefined; OSTM1 and ClCN7 mutations were associated with poor neurologic outcome. Among 9 patients with TCIRG1 defects, 6 presented with hypo-gammaglobulinemia, and 1 showed primary pulmonary hypertension. A total of 14 patients received HSCT; of these, 9 are alive and 8 of them have evidence of osteoclast function. The authors concluded that these data may provide a basis for informed decisions regarding the care of patients with IMO.
Gassas et al (2011) noted that HSCT has been used as therapy for selected inherited metabolic and genetic diseases (IMGDs). The primary objective of HSCT for these disorders has been to promote long-term survival, optimize quality of life, and improve neurocognitive performance. These researchers performed 45 HSCTs for 44 children with IMGDs (13 related and 32 unrelated); 24 HSCTs for 23 children with Hurler syndrome, 8 for IMO, 6 for X-linked adrenoleukodystrophy, 2 for metachromatic leukodystrophy, 2 for Gaucher disease, 1 for ganglioside monosialic acid (GM) gangliosidosis, 1 for sialiosis (type 2), and 1 HSCT for Niemann-Pick type A. At a median follow-up of 7.2 years (range of 2.2 to 17.6 y) 18 of 23 patients with Hurler syndrome are alive, 15 attended regular school; 13 of 18 were ambulatory, 2 had mobility difficulties, and 1 uses wheelchair. For non-Hurler patients, 5 children suffered secondary graft failure and 4 of them died from progressive disease. The remaining children with IMO are alive and most children attended regular school. One out of the 4 survivors with adrenoleukodystrophy has been transferred to the adult follow-up clinic and he is in full-time employment. Parents' perspectives and expectations of HSCT in these IMGDs were positive and supportive to continue to offer HSCT for these disorders.
Usta and colleagues (2012) stated that IMO presents early in life with extreme sclerosis of the skeleton and reduction of bone marrow spaces. Since there is a defect in the bone marrow, the disease can cause anemia, extra-medullary hematopoiesis secondary to anemia leading to hepato-splenomegaly, cranial nerves compression and severe growth failure. This disorder is often lethal within the first decade of life because of secondary infections. Stem cell transplantation remains the only curative therapy. These investigators reported on the case of a 2-month old male infant, diagnosed as IMO while investigating the cause of hepato-splenomegaly. The patient was referred for HSCT. The authors concluded that IMO should be kept in mind as a rare cause of hepato-splenomegaly and the patient should be referred for stem cell transplantation before neurologic or visual impairment develops.
Zhu and colleagues (2012) performed a retrospective analysis on 8 patients with IMO who underwent HSCT during the period from 2006 to 2011. Eight cases (4 females and 4 males, mean age of 13.5 months at HSCT) were diagnosed as IMO. Conditioning regimen included fludarabine, busulfan and cyclophosphamide. All patients received cyclosporine for prophylaxis of GVHD. A UMD recipient underwent CD34(+) cell selection. ATG/ALG, mycophenolate mofetil (MMF) and methotrexate (MTX) used for recipients with unrelated cord donor (n = 2) and recipients with haplo-identical donors n = (5). Average time for neutrophil engraftment was 15.7 day (9 to 36), platelet engraftment was 43.3 day (10 to 68). Patients were followed-up from 47 days to 5 years; 1 patient died of post-transplant complications. Seven cases presented better in clinical manifestation. Acute GVHD I° to II° was observed in 6 patients, III° to IV° in 2 patients. It was controlled by anti-GVHD therapy. The authors concluded that non-allogeneic HSCT treatment of infantile IMO showed high survival rate and restoration of hematopoiesis in haploid transplant patients, therefore, non-allogeneic HSCT may be an option to treat IMO in children.
Buchbinder and associates (2013) stated that IMO is a congenital disorder of osteoclast differentiation or dysfunction. Inadequate bone resorption by osteoclasts results in a spectrum of complications including hypocalcemia, osteo-sclerosis, marrow failure, extra-medullary hematopoiesis, hydrocephalus, visual deficits, and eventual mortality. Early diagnosis and timely HSCT is a recommended treatment approach for select patients prior to the development of end-organ damage. A co-morbid bleeding disorder presents a unique challenge in the setting of IMO and cord blood HSCT given the additional risk factors for bleeding including delayed engraftment, a high risk of developing sinusoidal obstruction syndrome, and potential need for emergent invasive procedures. To the authors' knowledge, this was the first report of a patient with an autosomal recessive form of IMO who successfully underwent a cord blood HSCT complicated by the presence of mild hemophilia A and HSCT-related complications including delayed engraftment, sinusoidal obstruction syndrome, and need for multiple invasive procedures (e.g., ventriculostomy, tracheostomy) without clinically significant bleeding.
Ott and associates (2013) stated that autosomal recessive osteopetrosis (ARO, MIM 259700) is a genetically heterogeneous rare skeletal disorder characterized by failure of osteoclast resorption leading to pathologically increased bone density, bone marrow failure, and fractures. In the neuronopathic form neurological complications are especially severe and progressive. An early identification of the underlying genetic defect is imperative for assessment of prognosis and treatment HSCT. These researchers describe for the first time homozygous microdeletions of different sizes affecting the OSTM1 gene in 2 unrelated consanguineous families with children suffering from neuronopathic IMO. Patients showed an exceptionally severe phenotype with variable CNS malformations, seizures, blindness, and deafness. Multi-organ failure due to sepsis led to early death between 6 weeks and 5 months of age in spite of intensive care treatment. Analysis of the break-points revealed different mechanisms underlying both re-arrangements. Microdeletions seem to represent a considerable portion of OSTM1 mutations and should therefore be included in a sufficient diagnostic screening.
Essabar et al (2014) reported on the case of a 13-month old male patient, diagnosed as IMO while investigating the cause of hepato-splenomegaly associated with hydrocephalus. His medical history revealed non consanguineous parents and 1 brother's death at the same age of unknown etiology (similar symptoms). Systemic examination showed hepato-splenomegaly, growth failure, developmental milestones delay, and rickets features. Ophthalmic exam yielded bilateral optic atrophy. Skeleton radiographs detected generalized dense bone and rickets. Cerebral CT scan revealed hydrocephalus. Histological examination showed hypoplastic bone marrow and extra-medullary hematopoiesis. Diagnosis was confirmed by genetic testing that showed 2 heterozygote mutations within the TCIRG1 gene. The patient received supportive treatment. He died from an acute respiratory distress. The authors concluded that IMO should be kept in mind as a rare cause of hepato-splenomegaly. Timely HSCT is the only curative approach for an otherwise fatal disease; it should be performed early before the irreversible neurologic impairment. Hematopoietic stem cell transplantation replaces abnormal osteoclasts with normal cells, given the high associated morbidity and mortality it is reserved only for the most severe cases of osteopetrosis. Successful results have been achieved in patients transplanted with allogeneic donor stem cells. Furthermore, non-allogeneic HSCT may be an option to treat IMO, it showed high survival rate and restoration of hematopoiesis in haploid transplant patients.
There was a phase II/III clinical trial on "Hematopoietic Stem Cell Transplantation for Malignant Infantile Osteopetrosis". However, the status of this trial is unclear because the information has not been verified since May 2012. Inclusion criteria were (i) diagnosis of osteopetrosis confirmed by bone biopsy and radiographic imaging, and (ii) age up to 5-year old. Exclusion criteria were (i) bilirubin greater than or equal to 3 mg/dL, (ii) carbonic anhydrase II deficiency osteopetrosis variant, (iii) creatinine clearance less than or equal to 40 ml/min/1.73 m2 or renal tubular acidosis, (iv) current severe infection, (v) evidence of CNS involvement, (vi) morbidity such as blindness or deafness, and (vii) serum glutamic pyruvic transaminase (SGPT) greater than or equal to 500 U/L. http://www.clinicaltrials.gov/ct2/show/NCT01087398.
Acyl-CoA Oxidase Deficiency:
Wang et al (2014) stated that acyl-CoA oxidase (ACOX1) deficiency is a rare disorder of peroxisomal very-long chain fatty acid oxidation. No reports detailing attempted treatment, longitudinal imaging, or neuropathology exist. These researchers described the natural history of clinical symptoms and brain imaging in 2 siblings with ACOX1 deficiency, including the younger sibling's response to allogeneic unrelated donor HSCT. These investigators conducted retrospective chart review to obtain clinical history, neuro-imaging, and neuropathology data. ACOX1 genotyping were performed to confirm the disease. In-vitro fibroblast and neural stem cell fatty acid oxidation assays were also performed. Both patients experienced a fatal neurodegenerative course, with late-stage cerebellar and cerebral gray matter atrophy. Serial brain MRI in the younger sibling indicated demyelination began in the medulla and progressed rostrally to include the white matter of the cerebellum, pons, midbrain, and eventually subcortical white matter. The successfully engrafted younger sibling had less brain inflammation, cortical atrophy, and neuronal loss on neuro-imaging and neuropathology compared to the untreated older sister. Fibroblasts and stem cells demonstrated deficient very long chain fatty acid oxidation. The authors concluded that although HSCT did not halt the course of ACOX1 deficiency, it reduced the extent of white matter inflammation in the brain. Demyelination continued because of ongoing neuronal loss, which may be due to inability of transplant to prevent progression of gray matter disease, adverse effects of chronic corticosteroid use to control GVHD, or intervention occurring beyond a critical point for therapeutic efficacy.
I-Cell Disease (Mucolipidosis Type II):
Lund et al (2014) stated that mucolipidosis type II (MLII), or I-cell disease, is a rare but severe disorder affecting localization of enzymes to the lysosome, generally resulting in death before the 10th birthday. While HSCT has been successful in treating some lysosomal storage diseases (LSD), only 2 cases have been reported on the use of HSCT to treat MLII. These investigators described the combined international experience in the use of HSCT for MLII in 22 patients. Although 95 % of the patients engrafted, overall survival (OS) was low, with only 6 patients (27 %) alive at last follow-up. The most common cause of death post-transplant was cardiovascular complications, most likely due to disease progression. Survivors were globally delayed in development and often required complex medical support, such as gastrostomy tubes for nutrition and tracheostomy with mechanical ventilation. The authors concluded that although HSCT has demonstrated effectiveness in treating some LSD, the neurologic outcome and survival for patents with MLII were poor. Thus, they stated that new medical and cellular therapies should be sought for these patients.
Combined Haploidentical Stem Cell Transplantation with Umbilical Cord Blood for Cerebral X-Linked Adrenoleukodystrophy:
Jiang et al (2015) noted that childhood cerebral X-linked adrenoleukodystrophy is a rapidly progressive neurodegenerative disorder that affects central nervous system myelin and the adrenal cortex. Hematopoietic stem cell transplantation is the best available curative therapy if performed during the early stages of disease. Only 30 % of patients who might benefit from a HSCT will have a full human leukocyte antigen-matched donor, which is considered to be the best choice. These investigators presented the case of a 5-year old boy with cerebral X-linked adrenoleukodystrophy whose brain MRI severity score was 7 and who needed an immediate transplantation without an available full HLA-matched donor. These researchers combined haploidentical and UCB sources for transplantation and observed encouraging results. After transplantation, the patient showed neurological stability for 6 months and the level of very long chain fatty acids had decreased. By 1 year, the patient appeared to gradually develop cognition, motor, and visual disturbances resulting from possible mix chimerism. The authors concluded that transplantation of haploidentical stem cells combined with the infusion of UCB is a novel approach for treating cerebral X-linked adrenoleukodystrophy. It is critical to monitor post-transplant chimerism and carry out anti-rejection therapy timely for a beneficial clinical outcome. These preliminary findings need to be validated by well-designed studies.
|CPT Codes / HCPCS Codes / ICD-10 Codes
|Information in the [brackets] below has been added for clarification purposes.  Codes requiring a 7th character are represented by "+":
|ICD-10 codes will become effective as of October 1, 2015:
|CPT codes covered if selection criteria are met:
|Management of recipient hematopoietic progenitor cell donor search and cell acquisition
|Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic
|38207 - 38215
|Transplant preparation of hematopoietic progenitor cells
|Bone marrow harvesting for transplantation; allogeneic
|Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor
|Allogeneic lymphocyte infusions
|Hematopoietic progenitor cell (HPC); HPC boost
|CPT codes not covered for indications listed in the CPB:
|Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous
|Bone marrow harvesting for transplantation; autologous
|Hematopoietic progenitor cell (HPC); autologous transplantation
|HCPCS codes covered if selection criteria are met:
|Cord blood-derived stem-cell transplantation, allogeneic
|Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including: pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre- and post-transplant care in the global definition
|ICD-10 codes covered if selection criteria are met:
|Neonatal adrenoleukodystrophy [childhood-onset adrenoleukodystrophy]
|Krabbe disease
|Metachromatic leukodystrophy
|Other lipid storage disorders [Wolman's disease]
|Disorders of glycosaminogiycan metabolism [Mucopolysaccharidosis]
|Defects in post-translational modification of lysosomal enzymes [Mucolipidosis II, Mucolipidosis III]
|Defects in glycoprotein degradation [Alpha-mannosidosis] [Fucosidosis] [Mucolipidosis I]


text:
Robert Stephen "Steve" Dugger, 49, of Union City, died Monday, Oct. 22, 2007 near Halls.
He was a truck driver for Rogers Oil Company for 15 years and a member of Troy First Baptist Church.
Services will be at 2 p.m. Friday at Union City Second Baptist Church with Dr. Bobby Williams and the Rev. Eddie Mallonee officiating. Burial will be in Mount Ararat Cemetery near Troy. White-Ranson Funeral Home is in charge of arrangements.
The family will receive visitors at 4-8 p.m. Thursday at the church.
Survivors include his wife, Kathy Jean Conner Dugger; a daughter, Kim Dugger of Troy; a son, Craig Dugger of Union City; two sisters, Rhonda Killian and husband, Larry, of Rives and Tammy McIntosh and husband, Ted, of Union City; a brother, Ricky Dugger and wife, Carol, of Troy; a grandson, Rexx Dugger of Union City; and several nieces and nephews.
Pallbearers will be Roger Simpson, Larry Tucker, Mackie Austin, Mike Fussell, Everett Lyboldt, Ben Baker, Doyle McDaniel and Mike Harrison. Honorary pallbearers will be employees and truck drivers of Rogers Oil Company and members of the Fourth and Fifth Battalions, Aviation Regiment of the 101st Airborne Division Air Assault Team from Fort Campbell, Ky.

subset: commoncrawl


text:
Funeral services for Mrs. Colleen Speed, 71, of Webb, will be held at 10:30 a.m. Friday, Oct. 24, 2008, at Sacred Heart Catholic Church in Spencer. Rev. Allen Reicks will officiate the service.
Visitation will begin after 2 p.m. today with the family present from 6-8 p.m. at the Warner Funeral Home in Spencer.
There will be a vigil service at 5:30 p.m. tonight at the funeral home.
Interment will take place at Garfield Cemetery at 2 p.m. Friday following lunch at the church.
Colleen passed away Tuesday, Oct. 21, 2008, at Spencer Hospital.
Warner Funeral Home in Spencer is in charge of arrangements.


text:
This question already has an answer here:
I am preparing for my C# EXAM. I am confused about the answer to this question:
A program can use the
IEnumeratorinterfaces to do which of the following?
a. Use MoveNext and Reset to move through a list of objects.
b. Use foreach to move through a list of objects.
c. Move through a list of objects by index.
d. Use the yield return statement to make a list of objects for iteration.
My answer was b). But the book: MCSD Certification Toolkit says it is a).
Can someone tell me why? I realize that you can obtain the
Enumerator using
GetEnumerator() and then call the
MoveNext and
Reset methods to move through the list (and use
Current to access the current element referred to by the iterator). But isn't implementing
IEnumerable and
IEnumerator the reason for an object to be used in a
foreach loop?


text:
VakaVeronicaFollow VakaVeronica
30-year-old Female living in Cork, Cork Ireland
Suitably nuts; fun in all the right places. Have travelled Central Europe, Australia and have been to San Francisco CA. Have loved every moment of my travels and look forward to doing more!
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The Latin Quest (Until December 2016)
4 countries \ 37 days \ from US$9859 per person
Do it all, experience everything & make the most of this unbelievable journey. From the bustling Rio streets to quiet ancient temples, live volcanoes & beautiful beaches, you'll find that paradise doesn't exist in just one place.


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text:
the MIGHTY one by Aeolus06Watch
©2009-2016 Aeolus06
the Hero with the coolest hat
I've redone my old pic of Max into something better and I have to say that I'm much happier with the results.
Mighty Max (c) bluebird toys
I've redone my old pic of Max into something better and I have to say that I'm much happier with the results.
Mighty Max (c) bluebird toys
The intro of this old show...LEGEND
Definitely! Mighty Max is a fantastic cartoon!
This show, man... this show. Some of the episodes were really trippy. I thought I was so cool because I had a few of these toys. And can I just say, DRWAING HATS ARE DIFFICULT! You did good here.
I remember watching this show as a little kid. I don't remember much of it, but it was amazing! your art is awesome!
Do you have any idea if this series is on DVD?
Do you have any idea if this series is on DVD?
Too cool!
I so want this as a wallpaper
Loved the series,also loved the ending, quite unusual for a kids show at the time or even nowadays.
I loved how the cartoon series ended. EVERYONE DIED lol except max
Awesome picture. Great work!
Man, Might Max was the best growing up. Remember having that dragon island playset as a kid. Was freakin sweet.
Man, Might Max was the best growing up. Remember having that dragon island playset as a kid. Was freakin sweet.
Ah, one of Rob Paulsen's finest roles.
Damn man, I forgot about that cartoon. U too cold bro. I gotta get on your lv. man. Keep up the great work.
Man, I had forgotten how much I loved this show. Awesome pic!
Awesome! I used to watch this every AM before school, amazing lighting!!
Much thanks glad that you like it
Love this Pic and I love how you did teh effects of the hat im jealous this pic is EPIC compared to my Max Chibi lol
awesome job
awesome job
Much thanks I took alot of time on this to make it just right
Oh, my god! I used to love this show! In fact, I still do; it's stood the test of time fairly well over the years
Hells yeah, I loved that show!
mighty max is indeed the king of badasses with hats
I just finished watching this show for the 3rd time! X3 You're piece made me go all crazy inside! I LOVE IT! Especially the proportions, the background, and Max's smirk! XD
Long Live the Mighty One!
Long Live the Mighty One!
Wow, haven't seen that show in FOREVER.
I can hear Virgil calling for the cap bearer. I like the highlight effect with the M.
thanks I was hoping that would work
great show, great pic
holy shit might max! I use to watch this show alot back in elementary. This some good old school stuff right here.
Oh Mighty Max, you don't get shows like this anymore, which had a bigger body count than most cartoons, but we loved for that. Gotta say your perspective of the "Capbearer" is nice, is it possible for a Skullmaster in the future?
dude! i used to watch that show. awesome
Oh snap Mighty Max! I remember having three or so of those sets. Never kept track of the pieces back then, but I have fond memories of them! Good to see some art of 'im!
Please, excuse the following, but I totally remember this show and so enjoyed watching it when it was on. Thanks for remaking this. It's so great looking!
SQWEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEE!!!!! *^o^* MIGHTY MAAAX!!!!!
SQWEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEEE!!!!! *^o^* MIGHTY MAAAX!!!!!
Ah, Mighty Max. I always wanted that cap. lol


text:
A resounding YES in answer to that question! Spirituality can definitely be enhanced, enriched, and expanded upon. By experiencing imagery journeys, many people have found both their intuition and spirituality have increased. Often these types of journeys allow a person to discover, explore, and experience profound spiritual connection. It is the journey within where transformation truly takes place.
Some hypnotherapists are familiar with client centered imagery journeys. With these types of journeys, the hypnotherapist is more a facilitator to the client, as the client's journey develops throughout the process. This imagery style opens up opportunity for autonomous discovery on the client's part. The client's journey is their own.
One imagery process that can often be the beginning of expanded spirituality is to allow the client to find the Wise and Loving Something Within. This is a process that brings the client into a unique and connecting experience to some sort of Wise and Loving One that helps to solve issues, brings comfortable relief, and a feeling of being supported in a very loving way. Helping clients to find a way to trust and come to truly know their own inner guidance is often a first step.
In addition, many times Mythic and Archetypal imagery can also bring about profound insight, realization, and connection to beyond the physical. Deeper understanding may come forward as the client discovers and explores mythic symbols and images out of their known zone. As the client experiences these inner journeys, it becomes clear to them that they are on their transformational path toward actualization, wholeness, and moving forward in life.
Imagery is frequently found to be extremely powerful. Actually having communication with all the various images that occur during these journeys, the client becomes strengthened emotionally, physically, mentally, and spiritually.


text:
In a recent interview with People, Jennifer Lopez says her biggest disappointment was her failed marriage to
Gilmore Girls' Netflix revival is going full steam ahead, with a steady drip of
After two seasons of cult success, but not much else, HBO has opted to pull the plug on its comedy series
Tom Whedon, father of famed writer/director Joss Whedon, died Thursday at the age of 83. The...
The presumption of innocence is one of the most overworked phrases in the criminal justice system. For all its fame and usage the presumption of innocence is not mentioned anywhere in the U.S Constitution.
This clip from Fear the Walking Dead's Season 2 premiere is short, but it's...
CBS renewed 11 series on Friday: Blue Bloods,
� It may surprise you to learn that more Americans are killed in bathtub accidents than in acts of Islamic terrorism in a typical year. Of course, there are countless other causes of death that are far more common than acts of terrorism — but...
Without any big primaries or caucuses and with all of the debates over and done with -- you'd think the news cycle would be coming to a slow roll for Decision 2016. But this isn't your typical election cycle.
Apparently, the NFL wants everyone to go back to school, and I am not talking about a showing of the 1986 comedy classic �Back to School� staring Rodney Dangerfield.
Negan (Jeffrey Dean Morgan) has officially arrived. In the trailer for
Ardmore Directory
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| Tech Board
| New PC build HDD issue - MyNameIsInigoMontoya on 9/25/15 at 4:51 pm
I just assembled a new PC. Got an SSD for OS and HDD for storage. Installed Win 8.1 and upgraded to 10. I left the HDD unplugged for this, so there would be no issues. Now when I plug in the HDD, it doesn't seem to be working. I've plugged it into multiple SATA ports. The SATA cable and power cable ...View Topic - Replies (1)
| Tech Board
| Uverse audio only PCM - MyNameIsInigoMontoya on 7/2/15 at 10:55 am
I recently switched to Uverse. I have the box connected to my Denon receiver via HDMI, but for some reason, the audio is only coming over as PCM. I made sure the setting on my Uverse is set to "Surround sound" rather than "Stereo", but it's still not working properly. Any ideas?...View Topic - Replies (1)
| Tech Board
| Foscam issues - MyNameIsInigoMontoya on 5/26/15 at 9:24 am
I got a Foscam FI9821W v2 this weekend and got it set up, but I'm having issues with it. I keep having to reset it. The first time, Foscam support told me that I shouldn't have it running on port 80 because it could be interfered with. We moved it to :8090 and it was working fine, but again after a ...View Topic - Replies (3)
| Tech Board
| RING doorbell - MyNameIsInigoMontoya on 5/21/15 at 1:22 pm
Has anybody ever used the RING wifi video doorbell (or something similar)? [link=(http://www.amazon.com/Ring-Wi-Fi-Enabled-Video-Doorbell/dp/B00N2ZDXW2)]LINK[/link]...View Topic - Replies (5)
| Music Board
| Home recording interfaces and DAWs recs - MyNameIsInigoMontoya on 4/2/15 at 2:00 pm
I used to dabble with some home recording years back with a PreSonus Firebox. I was looking to get back into this and I'm sure that a lot has changed since then. What are some good interfaces and DAWs that aren't too crazy expensive. It's mainly going to be for me to mess with song ideas. I don't ne...View Topic - Replies (4)
| Tech Board
| Anybody use wireless transmitters for surround sound speakers? - MyNameIsInigoMontoya on 3/26/15 at 11:52 am
Buying a house with a vaulted ceiling in the den that doesn't provide access for me to run wires through the walls from across the room. We are replacing the carpet with tile, so I can't run wire underneath. I've looked into the wireless transmitters, but I don't know if they are reliable or will af...View Topic - Replies (0)
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| Average monthly cost of pool ownership - MyNameIsInigoMontoya on 3/4/15 at 8:11 am
We are looking at buying a new house and considering one with a pool. On average, what should we expect to spend monthly to have one? Maintenance, chemicals, increase in electric bill, etc. I'm just trying to see how viable of an option this is....View Topic - Replies (13)
| Tech Board
| Amazon Fire Stick/TVMC performance question - MyNameIsInigoMontoya on 2/11/15 at 8:44 am
Got my Fire Stick yesterday and got TVMC installed (Thanks to this forum). I used Genesis to watch American Sniper and my streaming performance was less than desirable. Some parts were damn near unwatchable. I have Netflix/Amazon Prime movies that I stream from my XBOne wirelessly on the same TV and...View Topic - Replies (1)
| Tech Board
| Opinions wanted on my PC build - MyNameIsInigoMontoya on 10/21/14 at 11:11 am
I'm building a new PC and this is what I'm considering. I'd appreciate any criticism/input from you guys that know a whole lot more than I do about this. I;m not a hardcore gamer or anything, but I want a decent machine. I will be doing some audio recording and editing, though. Thanks in advance...View Topic - Replies (5)
| Tech Board
| Best AV Receiver around $500 - MyNameIsInigoMontoya on 10/6/14 at 8:50 am
I have a Denon AVR-1800 that has been very good to me for the last 10 years or so. I'm looking for something that supports 2 zones and HDMI. I know most receivers nowadays handle both of these, but I haven't researched much in quite a while. What are your recommendations? I'm looking at the followin...View Topic - Replies (5)
| Music Board
| River City RockFest - San Antonio - MyNameIsInigoMontoya on 2/12/14 at 7:27 am
Anybody ever been to this? [link=(http://rivercityrockfest.com/)]LINK[/link] This year's lineup: Kid Rock Five Finger Death Punch Deftones Seether Black Label Society Killswitch Engage Black Stone Cherry Hellyeah Redlight King Skindred Heroine Texas Kyng Butcher Babies Eve to Adam ...View Topic - Replies (0)
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| Woodlands/Houston recommendations for places to go/eat/etc - MyNameIsInigoMontoya on 9/25/13 at 10:40 am
Going to be moving to The Woodlands with the fiancee and two daughters pretty soon. I know a lot of you live around there, so I'm looking for some ideas on things to do, places to eat, where to watch LSU games, etc. So far, I have the following Kid's Entertainment: Main Event Splashtown Childr...View Topic - Replies (17)
| Movie/TV Board
| ASOIAF books too mature for pre-teen? - MyNameIsInigoMontoya on 6/5/13 at 3:02 pm
I have not read the books yet, but I's a huge fan of the show. My 12 year old daughter loves to read and would like the story, but the series is entirely too mature for her. Are the books as graphic as the show? Appropriate for an almost 13 year old to read?...
Posted on Movie/TV BoardView Topic - Replies (12)
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| Dog parks in BR - MyNameIsInigoMontoya on 5/31/13 at 7:51 am
Which ones are decent? I know there's one on Harrel's Ferry and one on Burbank. I have a big dog, so I definitely need one that has separate areas for little ankle-biters. ...View Topic - Replies (6)
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| Dead guy at RaceTrac on Sherwood - MyNameIsInigoMontoya on 5/9/13 at 11:46 am
Laying on the ground between the pump and his truck with a tarp over him. No clue what happened. [img]http://i1287.photobucket.com/albums/a634/InigoMontoya123/1471B0F0-0952-4073-A1E7-80C34333575D-8391-000006DAA534E27E_zpsd9763b6f.jpg[/img]...View Topic - Replies (19)
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| Dryer repair man around BR? - MyNameIsInigoMontoya on 4/19/13 at 8:27 am
Anybody have any recommendations on a handy man to take a look at a dryer that's not working? I have no idea if it's just the heating element or not, but I don't want to screw it up worse by fooling with it myself. lol...View Topic - Replies (6)
| Music Board
| Guitar players: guitar maintenance - MyNameIsInigoMontoya on 4/15/13 at 8:03 am
I just got my electrics back from being in storage for a while. Thankfully, they seem to be in great shape still. I'd like to bring them someplace and have them checked out, though (see if truss rod needs adjusting, lemon oil the fretboard, clean a little oxidation off the bridges and pickup covers,...View Topic - Replies (1)
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| Experience with Catahoula Leopard Dogs? - MyNameIsInigoMontoya on 4/7/13 at 5:42 pm
Anybody ever owned one of these? I'm looking to rescue a puppy and I come across quite a few of these (or at least mixes of them). Are they good with kids? How much exercise do they need daily? Any other info is appreciated. TIA...View Topic - Replies (13)
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| Summer Camps in BR or AP? - MyNameIsInigoMontoya on 4/2/13 at 12:28 pm
My 10 year old Goddaughter is coming to stay with us this summer for a couple of weeks and I'm looking for something for her to do during the day while I'm at work. She's into cheering and softball and other sports. Does anybody have any recommendations on day camps (either Ascension or EBR) that wo...View Topic - Replies (1)
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| I-12 east backed up past the split - MyNameIsInigoMontoya on 3/28/13 at 4:19 pm
Wreck at 12 by Airline exit...View Topic - Replies (2)
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How to Create Gorgeous Brows
Here are a few things to keep in mind when filling and shaping your brows with mineral makeup:
- If you have blond brows, filling in with a slightly deeper shade like Alima's Ash or Blond Satin Matte Eyeshadow will give you a little extra definition.
- Use the 'pencil rule' for general shape. Place a pencil alongside your nose. Your brows should begin at the edge of the pencil. Next, angle the pencil from your nose to the outer corner of your eye. Your brow should end roughly where it meets the pencil. Finally, look straight ahead in the mirror. The highest point of your arch should be approximately over the outer edge of your pupil.
- To highlight the drama of your brows, apply a bit of light, shimmery eyeshadow under the highest point of the arch.
- To keep your left and right brows as similar as possible, go back and forth as you add color; don't do one brow completely and then move on to the next.
- Your brows don't need to be perfect mirror images of each other. Think of them more as sisters than identical twins.
Any questions? Ask an Artist. Every question is a good one.


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I'm expecting our first baby and we're not finding out what we are having. My sister suggested post baby shower. I've since heard they are called a Sip and See or Meet and Greet party. I love the idea of this especially since we are not finding out the sex of the baby. I've been searching the internet for Save the Date wording ideas and I'm not having any luck. Any suggestions out there for wording on a post baby, baby shower?
Save the Date Wording
Last edited 02/13/2012
Comments (1)
Posted 02/15/2012
Why not call it a Meet the baby bbq or party
Soft Sheldon, warm Sheldon, little friend named Spock...Happy Sheldon, Sleepy Sheldon, knock knock knock.


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Niagara hunter takes trophy bear
September 30, 2015 Nicky Garvaglia of Niagara, Wis. shot this bear on Sept. 21 in Marinette County. Nicky was hunting with her dad, Todd Garvaglia. The bear dressed out at 434 pounds and was shot at eight yards away. more »»
Trout Unlimited to hold annual meeting
September 30, 2015 MARQUETTE —The Fred Waara Chapter of Trout Unlimited will hold its annual meeting Wednesday, Oct. 7. The meeting will take place in the Board Room of the Landmark Inn in Marquette. more »»
DNR makes Lake Gogebic walleye recommendation
September 30, 2015 LANSING — Michigan Department of Natural Resources fisheries biologists have recommended a change in the sportfishing regulations for walleyes in Lake Gogebic in the western Upper Peninsula. more »»
Land protected at Victoria Lake
September 30, 2015 IRONWOOD?— Long-sought public access to Victoria Lake and the Ontonagon River has been secured in a 245-acre addition to the Ottawa National Forest, The Trust for Public Land and U.S. more »»
'Ask the DNR' to air Thursday on Channel 13
September 30, 2015 MARQUETTE — Michigan Department of Natural Resources staff will appear on Thursday night's call-in question program "Ask the DNR" on Public Television from WNMU-TV13 in Marquette. more »»
Anglers, hunters finding success
September 26, 2015 IRON MOUNTAIN — Outdoors enthusiasts are enjoying the final days of September, highlighted by continued fishing success and the beginning of several hunts. more »»
September 26, 2015 Mike Miller, 15, of Channing, harvested a 10-point buck in Delta County during Michigan's youth hunt. The buck's rack has an inside spread of 18 inches. more »»
Group works to establish whooping crane population
September 24, 2015 PRINCETON, Wis. – Members of the whooping crane class of 2015 are getting ready for their next big adventure: migration. more »»
Wisconsin DNR board approves permanent three-walleye limit
September 23, 2015 MADISON, Wis. (AP) — The Wisconsin Department of Natural Resources' board has adopted a permanent three-walleye limit for non-tribal anglers on lakes and rivers within Wisconsin's ceded territory. more »»
Michigan deer hunt today, Sunday
September 19, 2015 IRON MOUNTAIN — Temperatures should be in the 60s to near 70 this weekend for Michigan's Liberty Hunt. more »»
DNR advisory panel to meet in Ontonagon County
September 19, 2015 MARQUETTE?—Participants in Monday's Western Upper Peninsula Citizens' Advisory Council meeting are scheduled to hear a presentation on state forest road funding and updates on the Michigan Departmen... more »»
Ruffed Grouse Society dinner set for Oct. 1 at Pine Mountain
September 19, 2015 Iron MOuntain — The North Woods Chapter of the Ruffed Grouse Society will host its 11th annual Conservation and Sportsmen's Banquet on Thursday, Oct. 1, 2015 at the Pine Mountain Golf & Ski Resor. more »»
River bass
September 19, 2015 While fishing on the Menominee River this summer, 12-year-old Seth Conery landed these two smallmouth bass, each measuring nearly 18 3/4 inches. They were caught one cast apart using his trout pole. more »»
Merriman archery club members dominate U.P. competitive meet
September 14, 2015 MERRIMAN — Members of the Merriman United Sportsmen's Archery Club competed in the annual Upper Peninsula Field Archery Association Championship hosted by Straight Line Archery in Ishpeming. more »»
Trout picks up; fall hunting begins
September 14, 2015 IRON MOUNTAIN — With anglers reporting nice catches of trout and northern, among others, on local waters, fall fishing in the area is off to a strong star. more »»
Fishing remains steady; hunters prep for fall
September 5, 2015 IRON MOUNTAIN — While Labor Day weekend may herald the "end of summer," outdoors enthusiasts are preparing to make the most of the coming fall. more »»
Bear season set to begin
September 5, 2015 MADISON, Wis. (AP) — Wisconsin's bear hunting season is set to begin next week. The season is slated to begin on Sept. 9 and run through Oct. 13. more »»
Antlerless deer results posted; remaining licenses on sale Sept. 9
September 5, 2015 LANSING — The Michigan Department of Natural Resources reminds hunters to check their antlerless deer drawing results and availability of remaining licenses at www.michigan.gov/huntdrawings. more »»
Michigan gets federal grant to expand hunting access program
September 5, 2015 LANSING (AP) — The Michigan Department of Natural Resources has received federal funding to expand a program that pays private owners to let the public use their land for huntin. more »»
Eagle River Area Ladies Ducks Unlimited to meet
September 5, 2015 EAGLE?RIVER, Wis. — The Eagle River Area Ladies Chapter of Ducks Unlimited will be holding its annual fundraising banquet on Monday, Sept. 14, at the Oneida Village Inn in downtown Three Lakes, Wis. more »»
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Free forum : The 1st Forum for Professionals in the Tonsorial Arts
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Multimedia: Waldo Canyon Fire
- View aerial images of the Waldo Canyon Fire.
- View before and after images of fire damage in the Mountain Shadows subdivision.
- View a slideshow of the Waldo Canyon Fire.
- View a slide show of President Obama touring the Waldo Canyon Fire site.
- Watch video of the Waldo Canyon Fire.
- Watch raw video of a family escaping the Waldo Canyon Fire.
- Jun 26:
- Waldo Canyon fire: A year later, life returning to normal
- Feb 27:
- Report: Mass call systems 'underperformed' during Colorado's Waldo Canyon Fire
- Jan 30:
- Gov. John Hickenlooper lifts part of Lower North Fork fire burn ban
- Jan 17:
- 4,167 Colorado wildfires caused record losses of $538 million in 2012
- Nov 25:
- Rising threats to homes lands Colorado among catastrophic states
- Jun 26:
- Colorado wildfire: thousands evacuated in Colorado Springs
- Nov 6:
- Waldo Canyon fire could bring economic benefits
- Nov 1:
- Juvenile charged with starting $10 million Weber Fire near Mancos
- Oct 24:
- Report: Colorado Springs wasn't slow to order Waldo Canyon evacuations
- Oct 23:
- Report: City was not slow to order Waldo Canyon evacuations
- Oct 19:
- Waldo fire volunteer faces sex assault charge
- Oct 14:
- Neighborhood devastated by Waldo Canyon fire rising again
- Oct 1:
- Coroner officially IDs victims of Waldo Canyon fire
After burning for two weeks and destroying 347 structures in and to the west of Colorado Springs, the Waldo Canyon fire was expected to be fully contained Friday.
The Type 1 Incident Management Team that has been fighting the fire will transfer command to a Type 3 team Saturday morning, according to a news release.
The team said they would like to thank the community for "all the wonderful support" they've been shown during their time in the area.
The blaze is at 18,247 acres as of Friday morning and has cost approximately $15.3 million to fight.
No structures are threatened at this time.
Mandatory evacuations for another 76 homes in the Mountain Shadows neighborhood were lifted around 5 p.m. Friday, according to the city of Colorado Springs. The city said there are still some people evacuated, but did not have a number available.
Residents on the following streets were allowed home Friday afternoon: Wilson Road, Jenner Court, Brogans Bluff Drive, Karamy Court, Tamora Way and Ravina Court.
The U.S. Forest Service said it will still maintain several closures, however, while firefighters continue to mop up hot spots and work on rehabilitation.
One to 2 inches of rain were expected to hit the fire area Friday and Saturday, with cooler temperatures and higher humidity rolling in.
According to the Forest Service, Colorado has seen more than a dozen fires this season.
Fire facts
The Waldo Canyon fire was expected to be declared 100 percent contained Friday, while fires in High Park and Flagstaff had already been declared fully contained.
A week ago, the three large Front Range blazes had more than 3,000 firefighters working around the clock. But thanks to their work and an aggressive aerial response, all three have been halted.
The tally:
Waldo Canyon: Two killed, 347 structures destroyed, 18,247 acres burned, cause undetermined. It ranks as the most destructive fire in Colorado history
High Park: One killed, 259 homes destroyed, 87,284 acres burned, caused by lightning
Flagstaff: No deaths, no homes destroyed, 300 acres burned, caused by lightning
Firefighters are now moving to other major blazes in the west, including the Little Sand fire near Pagosa Springs, which started on May 13 and remains only 40 percent contained after burning 24,900 acres. Two Wyoming fires, Squirrel Creek and Arapaho, are so large that their smoke clouded views in Denver on Thursday. Those two alone have more than 1,700 firefighters working the lines.


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Qorilazo Group
Update on Qorilazo GroupThe members belong to the Qorilazo communal bank. The bank is in the Cusco district, province, and department.
Tomasa, age 52, is married and has two children. She works in her business of selling corn in an itinerant manner. She takes the corn to the different places where "chicha" , which is a corn based drink, is sold. She works from 8:00 a.m. until 6:00 p.m. It is through this work that she gets her children ahead. Her dream is to have a place where she can sell the corn.
She is requesting the loan to buy corn wholesale.
The other members devote themselves to the restaurant business, the business of selling food, the business of raising animals, the business of a grocery store, and the business of selling potatoes.
She is grateful to those who are part of this dream and pledges to repay in a timely fashion.
La socia es la Sra. Tomasa ella es casada y tiene 52 años y tiene 2 hijos; La socia trabaja con su negocio de venta de maíz, ella vende maíz en forma ambulatoria, la socia lleva maíz a las diferentes lugares donde venden chicha que es una bebida a base de maíz, la socia trabaja desde las 8:00 a.m hasta las 6:00 p.m,por medio de este trabajo la socia saca adelante a sus hijos, el sueño de la socia es tener un local donde pueda vender el maíz. La socia solicita el préstamo para comprar maíz al por mayor.
Los otros socios se dedican al negocio de restaurant, negocio de venta de comida, negocio de crianza de animales, negocio de tienda de abarrotes y negocio de venta de papa.
La socia agradece a quienes forman parte de este sueño mediante este medio y se compromete a cumplir con el pago de sus cuotas en el plazo establecido.
Previous Loan DetailsThese members belong to the Qorilazo communal bank. This bank is located in the district of Cusco, which is part of the province and department of Cusco. One of the members is Señora Yeni. She is 27 years old, is in a common-law marriage, and has two children. Her business is a grocery store. ... More from Qorilazo Group's previous loan »
Additional Information
Important InformationAbout Asociación Arariwa
Asociación Arariwa is a large non-governmental organization that started offering microcredit in 1994 to improve the quality of life, skills and equity of the population in the rural Cusco region of Peru. Arariwa serves the southern Andean provinces of Peru, and is distinguished by its efforts to reach the very poor, who often live in isolated rural areas. Arariwa fosters village banking, supports savings accounts, promotes access to education, and empowers women entrepreneurs (who make up 78% of its borrowers).
Concurrent and Successive Loans
Our Field Partners often work with borrowers over a series of loans as the borrowers build credit, take out bigger loans, and expand their businesses. In order to make it easier for our Field Partners to post loans for borrowers who have been listed on Kiva before, we allow them to post successive and concurrent loans for their Kiva borrowers. This means that our Field Partners are able to post a borrower's second, third, etc., loan on Kiva without having to re-enter all of the borrower's information.
This borrower has been listed on Kiva before, so you'll see an updated loan description, as well as excerpts of the original descriptions from earlier loans. Most borrowers take out loans consecutively, meaning that they receive a second loan after having repaid the first. However, sometimes our Field Partners give out concurrent loans, allowing borrowers to take out one primary loan and a secondary "add-on" loan along with it. These "add-on" loans are typically smaller than the borrower's primary loan and serve a different purpose. Because Field Partners can now post loans as successive and concurrent loans, you will be able to track borrower progress over time and see the various ways a borrower is working with our Field Partners through funds from Kiva's lenders.
This is a Group Loan
In a group loan, each member of the group receives an individual loan but is part of a larger group of individuals. The group is there to provide support to the members and to provide a system of peer pressure, but groups may or may not be formally bound by a group guarantee. In cases where there is a group guarantee, members of the group are responsible for paying back the loans of their fellow group members in the case of delinquency or default.
Kiva's Field Partners typically feature one borrower from a group. The loan description, sector, and other attributes for a group loan profile are determined by the featured borrower's loan. The other members of the group are not required to use their loans for the same purpose.
About Peru
85View loans »
Success!! The loan was 100% repaid
- Repayment Term
- 6 months (Additional Information)
- Repayment Schedule
- Monthly
- Pre-Disbursed:
- Apr 20, 2012
- Listed
- May 14, 2012
- Currency Exchange Loss:
- Possible
- Ended:
- Sep 15, 2012


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This week's report by the Congressional Budget Office won't settle the decades-old argument about whether low-income families are hurt or helped by raising the national minimum wage.
However, because it clearly lays out the trade-offs that flow from higher government wage floors, the CBO has injected a big dose of intellectual honesty into the debate.
President Barack Obama and congressional Democrats want to increase the federal minimum to $10.10 from $7.25 an hour.
But that could cause 500,000 workers across the U.S. economy to lose their jobs in the second half of 2016, the CBO said in a report released Tuesday. On the other hand, it would boost incomes of 16.5 million low-wage workers and lift 900,000 families out of poverty.
In other words, there's a trade-off: 500,000 workers could see wages fall to zero so that 16.5 million can receive fatter paychecks averaging $300 a year.
In California, politicians have already decided such trade-offs are worth making, passing a law that raises the state minimum to $9 in July and $10 in 2016. And Interim Mayor Todd Gloria has called for a November referendum that would create a presumably higher minimum wage in San Diego.
For those who question how a higher wage floor could hurt anybody, the CBO predicted the new federal minimum would push up prices slightly for some goods and services, causing consumers to spend less and forcing businesses to cut jobs or forego raises for higher-paid workers.
And the policy would force another trade-off. A $10.10 federal minimum would raise incomes for low-wage workers by $31 billion — but subtract $17 billion from families that earn six times the poverty level, which is about $120,000 a year for a family of three.
From this perspective, raising the minimum wage looks more like a classic government transfer of wealth. Some people lose their jobs or see incomes fall so that somebody else can get a mandatory raise, regardless of performance.
Bear in mind that this analysis comes from the numbers-crunching agency of Congress, which is technically nonpartisan but is in fact staffed with mostly liberal economists.
And there's nothing ironclad about the CBO's economic estimates. Indeed, the same report that estimates job losses at 500,000 also says they either could be "very slight" or reach 1 million workers.
Still, I find the report completely refreshing. Like most economic concepts, the minimum wage has been abused by partisans of every stripe, with Democrats dismissing the cost in terms of jobless families and Republicans exaggerating the cost to employers.
Among economists, the disagreement is more abstract and burns at a much lower level. After all, 500,000 job losses for a $31 billion raise is small potatoes in a national economy that employs 137 million people and produces $17.1 trillion in goods and services.
Everybody agrees that President Franklin Roosevelt enacted the first wage floor, 25 cents an hour, in 1938. The minimum peaked in 1968 at $1.60, which translates to $10.71 in 2013 dollars.
In 1968 unemployment averaged 3.6 percent and America dominated global commerce.
Today foreign competition and automation has destroyed millions of jobs. Real wages have stagnated or declined for most workers since the 1990s. The middle class has been shrinking since 1971.
Reversing such trends is probably impossible anytime soon. Higher foreign wages and rising U.S. energy production from "fracking" is causing some good jobs to return.
Yet many experts say the astonishing wave of automation that eliminated high-wage manufacturing and low-wage service jobs is poised to wash through higher wage tiers.
The honest truth is that federal government can do very little about such fundamental economic convulsions. And measures that would truly help — such as overhauling the tax code, balancing the budget and fixing unfunded entitlements — involve very hard political choices.


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The history of music is a history of performers continuously transcending what were thought to be limits, and maybe the simple existence of such challenging scores as Le marteau sans maître and Zeitmasze was enough to encourage a new race of modern virtuosos, who detected in postwar music an invitation to extend the possibilities of performance. This was something new. Virtuosity in previous ages had been the domain of the composer-performer, and where performers and composers were tied in personal and professional relationships, as with Brahms and Mühlfeld or Stravinsky and Dushkin, the result was not a wild extrapolation of technique. But music now was in an extreme situation, and the new music of the 1960s, especially, was often a music of extreme and unprecedented demands. The rapid turnover in compositional technique was paralleled by rapid extensions of what could be expected from instruments and voices -- extensions which eventually took on a life of their own, as instrumentalists began to feel that composers were not necessary, that virtuosity had its best display as improvisation.
The revolution in performance practice, at its height in the mid- 1960s, had effects which defy easy summary. Woodwind players found it possible to produce 'multiphonics' (i.e. chords), either by using particular fingers or by singing into their instruments; they could also make percussive noises (by tapping on parts of the instrument), microtones, and unusual sounds created by means of more or less severe alterations to the embouchure and mouthpiece. Many of these devices were also found possible on brass instruments. On strings, new sounds could be obtained by unconventional bowing pressures, by bowing on unconventional parts of the instrument, by striking the instrument in various ways, and so on. Changes in piano technique have tended to be more straightforward tightenings of traditional demands in terms of dexterity, but percussionists have found vastly wider scope, in terms of their instrumentaria, their techniques, and their musical importance. It is enough to note that a virtuoso percussionist could hardly have existed in western music before the 1950s -- Stockhausen had to write Zyklus because no test pieces for the species existed -- whereas percussion ensembles and soloists are now a normal part of musical life.
The simplest possible response to these new riches is to use them as extensions of timbral resource, without letting them influence the premises of creative


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Mo. House endorses June primary election date
Wednesday, April 23, 2014
JEFFERSON CITY, Mo. (AP) -- The Missouri House gave initial approval to legislation that would move the state's primary elections to June.
Party primaries for Congress, the state Legislature and statewide offices are currently held in even-numbered years on the Tuesday after the first Monday in August. But the bill endorsed on Wednesday would move the primaries to the first Tuesday after the third Monday in June.
Supporters say the earlier primaries would give the winners more time to compete for November's general election. But opponents argue it could also cause lawmakers to campaign more aggressively during the legislative session, which runs through mid-May.
The measure needs one more vote before moving to the Senate.
Primary is HB 1936
Legislature: http://www.moga.mo.gov
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