Current Pediatric Reviews - Volume 21, Issue 4, 2025
Volume 21, Issue 4, 2025
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Persistent Inflammation, Immunosuppression and Catabolism Syndrome in Pediatric Populations: A Brief Perspective
Authors: Michael D. Santarelli, Kelly A. Davis and Ryan J. StarkSurviving near-lethal insults, such as sepsis, trauma, and major surgery is more common due to advances in medical care. The decline in mortality has unmasked a population of chronic critically ill patients, many with the pathological immunophenotype known as Persistent inflammation, Immunosuppression, and Catabolism Syndrome (PICS). Though initially described in adults, many critically ill children exhibit the hallmarks of PICS, including lymphopenia, hyperinflammation, and evidence of ongoing somatic protein catabolism. These patients are plagued with recurrent infections and suffer worse outcomes. There remains a need to understand the pathophysiology underlying this condition to elucidate potential therapies and develop interventions. This perspective provides the most current update of PICS within the pediatric population.
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Is Necrotizing Enterocolitis and Spontaneous Intestinal Perforation Part of Same Disease Spectrum - New Insights?
Authors: Parvesh Garg, Padma Garg and Jeffrey ShenbergerThe diagnosis of NEC is based on the presence of pneumatosis, dilated bowel loops, portal venous gas, or pneumoperitoneum on the abdominal x-ray. Published studies suggest that the appearance of pneumatosis most likely depends on the gestational age, with a shift occurring between 27-28 weeks. For infants of gestational age under 27 weeks, pneumoperitoneum is the most likely presentation of bowel injury due to the thin bowel wall and the colonization of the gut with the non-gas-producing bacteria. Assessment of postoperative morbidity and white matter injury on the brain MRI at term equivalent age in a cohort of preterm infants failed to identify differences between SIP and NEC groups when confirmed by histology. These findings illustrate the difficulty in conclusively identifying cases as SIP or NEC, particularly when gestational age is considered and raise speculation that both conditions lie on the same spectrum of intestinal injury.
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Prune-belly Syndrome: An Update
The Prune-Belly (Eagle-Barrett) syndrome (PBS) is a congenital and genetically heterogeneous disease, more prevalent in males, defined by the clinical triad (1) deficiency of abdominal muscles, (2) bilateral cryptorchidism, and (3) urinary tract abnormalities. The abdomen of an infant with PBS has a typical appearance, similar to the aspect of a prune, which gives it its name. Although the etiology of this disorder is still unknown, numerous theories, mutations, and genetic disturbances have been proposed to explain the origin of PBS. Prognosis can differ a lot from one patient to another, since this condition has a wide spectrum of clinical presentation. Despite being a rare condition, the importance of PBS should not be underestimated, in the light of the potential of the disorder to lead to chronic kidney disease and other severe complications. In that regard, this review gathers the most up-to-date knowledge about the etiopathogenesis, clinical features, diagnosis, management and prognosis of PBS.
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Insights from Overviewing Selective International Guidelines for Pediatric Asthma
Authors: Kam L.E. Hon, Daniel K.K. Ng, Wa K. Chiu and Alexander K.C. LeungBackgroundAsthma is a chronic atopic and inflammatory bronchial disease characterized by recurring symptoms, episodic reversible bronchial obstruction and easily triggered bronchospasms. Asthma often begins in childhood. International guidelines are widely accepted and implemented; however, there are similarities and differences in the management approaches. There is no national guideline in many cities in Asia. This review aims to provide a practical perspective on current recommendations in the management of childhood asthma, specifically in the following aspects: diagnosis, classification of severity, treatment options, and asthma control, and to provide physicians with up-to-date information for the management of asthma.
MethodsWe used the PubMed function of Clinical Queries and searched keywords of “Asthma”, “Pediatric” AND “Guidelines” as the search engine. “Clinical Prediction Guides”, “Etiology”, “Diagnosis”, “Therapy,” “Prognosis,” and “Narrow” scope were used as filters. The search was conducted in November 2022. The information retrieved from this search was used in compiling the present article.
ResultsDiagnosis is clinically based on symptom pattern, response to therapy with bronchodilators and inhaled corticosteroids, and spirometric pulmonary function testing (PFT). Asthma is classified in accordance with symptom frequency, peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and atopic versus nonatopic etiology, where atopy means a predisposition toward a type 1 hypersensitivity reaction. Asthma is also classified as intermittent or persistent (mild to severe). Unfortunately, there is no disease cure for asthma. However, symptoms can be prevented by trigger avoidance and suppressed with inhaled corticosteroids. Antileukotriene agents or long-acting beta-agonists (LABA) may be used together with inhaled corticosteroids if symptoms of asthma are not controlled. Rapidly worsening symptoms are usually treated with an inhaled short-acting beta-2 agonist (SABA, e.g., salbutamol) and oral corticosteroids. Intravenous corticosteroids and hospitalization are required in severe cases of asthma attacks. Some guidelines also provide recommendations on the use of biologics and immunotherapy.
ConclusionAsthma is diagnosed clinically, with supporting laboratory testing. Treatment is based on severity classification, from intermittent to persistent. Inhaled bronchodilator and anti-inflammatory corticosteroid form the main stay of management.
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Pinworm (Enterobius Vermicularis) Infestation: An Updated Review
Authors: Alexander K.C. Leung, Joseph M. Lam, Benjamin Barankin, Alex H.C. Wong, Kin F. Leong and Kam L. HonBackgroundPinworm infestation is an important public health problem worldwide, especially among children 5 to 10 years of age in developing countries with temperate climates. The problem is often overlooked because of its mild or asymptomatic clinical manifestations.
ObjectivesThe purpose of this article was to familiarize pediatricians with the diagnosis and management of pinworm infestation.
MethodsA search was conducted in August 2023 in PubMed Clinical Queries using the key terms “Enterobius vermicularis,” OR “enterobiasis,” OR “pinworm.” The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article.
ResultsEnterobiasis is a cosmopolitan parasitosis caused by Enterobius vermicularis. It affects approximately 30% of children worldwide and up to 60% of children in some developing countries. Predisposing factors include poor socioeconomic conditions, inadequate sanitation, poor personal hygiene, and overcrowding. Children aged 5 to 14 years have shown the highest prevalence of enterobiasis.. Egg transmission is mainly by the fecal-oral route. Approximately 30 to 40% of infested patients do not show any clinical symptoms of the disease. For symptomatic patients, the most common presenting symptom is nocturnal pruritus ani. The diagnosis of E. vermicularis infection is best established by the cellophane tape test. The sensitivity of one single test is around 50%; however, the sensitivity increases to approximately 90% with tests performed on three different mornings. If a worm is visualized in the perianal area or the stool, a pathological examination of the worm will yield a definitive diagnosis. As pinworms and eggs are not usually passed in the stool, examination of the stool is not recommended. The drugs of choice for the treatment of pinworm infestation are mebendazole (100 mg), pyrantel pamoate (11 mg/kg, maximum 1 g), and albendazole (400 mg), all of the above-mentioned drugs are given in a single dose and repeated in two weeks. Mebendazole and albendazole are both adulticidal and ovicidal, whereas pyrantel pamoate is only adulticidal. Given their safety and effectiveness, mebendazole and albendazole are currently the best available drugs for the treatment of pinworm infestation. For pregnant women, pyrantel is preferred to mebendazole and albendazole. Treatment of all household members should be considered, especially if there are multiple or repeated symptomatic infections because reinfection is common even when effective medication is given.
ConclusionIn spite of effective treatment of pinworm infestation, recurrences are common. Recurrences are likely due to repeated cycles of reinfection (particularly, autoinfection) because of the short life span of adult pinworms. Good personal hygiene, such as frequent handwashing, especially after bowel movements and before meals, clipping of fingernails, avoidance of finger-sucking, nail-biting, and scratching in the anogenital area, are important preventive measures. Treatment of all household members should be considered, especially if there are multiple or repeated symptomatic infections.
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A Survey on Diagnosis and Prognosis of Prenatal Asphyxia based on Oxidant Antioxidant Balance: Evidence from a Systematic Review and Meta-analysis
Authors: Boskabadi Hassan, Amirkhani Samin, Tahereh Loghmani and Zakerihamidi MaryamIntroductionThe mechanism of occurrence and complications of asphyxia change in the treatment process and the future prognosis of newborns. One of the discussed mechanisms is the disruption of oxidant anti-oxidant balance. Therefore, the current study was conducted aiming to systematically review and meta-analysis in the diagnosis and prognosis of prenatal asphyxia based on oxidant-antioxidant balance.
MethodsA comprehensive electronic search was conducted with PubMed, Cochrane Library, Scopus, and Web of Science databases, up to February 2023 to identify relevant studies examining the association between Prooxidant anti-oxidant balance (PAB) and Malondialdehyde 1 levels with the risk of prenatal asphyxia. Only English studies were incorporated. The search terms used included Asphyxia, Diagnosis, Prognosis, Newborns, Prenatal, Oxidant antioxidant balance, and oxidative stress. A total of 13 studies were retrieved. Data regarding the standard mean difference (SMD) were collected, and a pooled SMD with 95%CI was calculated using a random-effect model to determine the strength of the relationship. Furthermore, the risk of publication bias was assessed through funnel plot and Egger’s linear regression tests. Inclusion criteria was 1) The studies conducted on neonates, diagnosis and outcomes of prenatal asphyxia, oxidants and antioxidants were included. Research conducted on adults or on animals or review articles, and articles which only their abstracts were available were excluded. The quality of the reported studies was also assessed.
ResultsOut of 980 searched articles, 13 articles (10 prospective articles and 3 cross-sectional articles) were studied. An increase in antioxidant enzymes (Glutathione peroxidase (GSH-Px), catalase (CAT) and Plasma superoxide dismutase (SOD)) cannot be dealt with excessive oxidants produced in the body (Plasma and cerebrospinal fluid levels of Malondialdehyde (MDA), free radical products (F8-isoprostane and MDA), saturated fatty acids and % CoQ-10). Prooxidant anti-oxidant balance (PAB) levels among neonates who had asphyxia were announced to be two times higher than normal newborns. PAB values in neonates with asphyxia, who had adverse prognosis, were about three times higher than those with favorable prognosis. The sensitivity of PAB in predicting the prognosis of neonates with asphyxia was reported 83- 89% and its specificity was 71- 92%. The pooled SMD analysis revealed a significant association between PAB and MDA levels with the risk of prenatal asphyxia both overall (SMD = 1.447, 95%CI: 0.961-1.934, P < 0.001), as well as separately in subgroups of PAB (SMD = 1.134, 95%CI: 0.623-1.644, P < 0.001) and MDA (SMD = 1.910, 95%CI: 0.916-2.903, P < 0.001).
ConclusionOur meta-analysis findings revealed the potential of evaluating antioxidant enzymes and oxidant agents, as well as assessing the balance between them (PAB), in diagnosing and predicting the prognosis of neonatal asphyxia. The limitations of the present study included not having access to all related complete articles, lack of quality and usability in reports of some articles, and the different diagnostic methods of prenatal asphyxia in different studies.
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Effects of Vitamin D and E Supplementation on Prevention of Bronchopulmonary Dysplasia (BPD) in Premature Neonates: A Systematic Review and Meta-analysis
BackgroundBronchopulmonary Dysplasia (BPD) has a multifactorial etiology. Vitamin E and vitamin D play an important role in lung development and can potentially be beneficial in the prevention of BPD.
ObjectivesThe study aimed to compare the risk of BPD occurrence in preterm neonates supplemented with vitamin D or E versus those who did not get supplementation.
MethodsThe literature search was conducted for this systematic review by searching the PubMed, Scopus, and Web of Science databases up to December 2022. Randomized controlled trials involved administering vitamin D or E to preterm neonates and examining the occurrence of BPD. We excluded non-English articles, and articles with non-relevant and insufficient data. We used the Critical Appraisal Skills Programme (CASP) checklist to assess the quality of the included studies. We used Egger’s test to evaluate the risk of bias among the included studies. Heterogeneity was also assessed through Q-test and I2. We applied the random effect model for analysis. A P-value less than 0.05 was considered as significant. All the statistical analysis in the current study was performed using STATA 14. The Relative Risk (RR) was calculated as the effect size with 95% Confidence Interval (CI).
ResultsThree eligible studies seeking the role of vitamin D in the prevention of BPD were analysed. Meta-analysis revealed that receiving vitamin D supplementation can significantly reduce the risk of BPD in preterm infants (RR = 0.357, 95% CI: 0.189-0.675, I2 = 0.0%; p = 0.002). Similarly, for assessing the role of Vitamin E in the prevention of BPD, three eligible studies were analysed. Vitamin E supplementation was not found to play a significant role in the reduction of BPD (RR = 0.659, 95%CI = 0.243-1.786, I2 = 38.7%; p = 0.412).
ConclusionVitamin D supplementation could be beneficial in preventing BPD in preterm infants. However, evidence is not enough regarding vitamin E's role in reducing the incidence of BPD in preterm infants.
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Strategies for Pain Management after Extraction of Primary Teeth: A Systematic Review of Randomized Clinical Trials
BackgroundIn dental extractions, particularly when local anesthesia is used, it usually offers analgesic relief for a few hours. However, pain can become a notable concern in the immediate postoperative period due to the trauma experienced by both soft and hard oral tissues.
ObjectivesThis systematic review aimed to evaluate the most effective strategies for managing postoperative pain in primary tooth extractions.
MethodsTwo examiners conducted a search across electronic databases: MEDLINE (via PubMed), Embase, Scopus, Web of Science, CENTRAL, and OpenGray. Studies were included if they met the following criteria after reviewing their titles and abstracts: they involved children and evaluated pain management following primary tooth extraction. Subsequently, articles that described extractions performed under any form of sedation, were not conducted under local anesthesia, in an outpatient setting, and in children aged 0 to 12 years, or were not randomized controlled trials, were excluded.
ResultsThe search yielded 374 relevant articles, of which 9 were included. Among these, 5 utilized preoperative medications as a pain management strategy, one evaluated low-level laser therapy (LLLT) postoperatively, one assessed calendula drops postoperatively, and another explored virtual reality during the procedure and arnica in solution both pre and postoperatively.
ConclusionAmong all the strategies evaluated, the strategy involving analgesics administered 30 minutes before tooth extractions was supported by better-designed studies. However, there is a high risk of bias.
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Early Outcomes of Hirschsprung's Disease after Definitive Surgery: A Ten-year Experience
IntroductionThis study aimed to examine the characteristics of Hirschsprung’s Disease (HD) in patients aged<18 who underwent surgical procedure at Dr. Zainoel Abidin (RSUDZA) General Hospital, Banda Aceh, Indonesia, between January 2010 and December 2020.
MethodsThis retrospective study collected and analyzed data from medical records of 18-year-old or younger children (n = 180) diagnosed with HD at RSUDZA. The surgical procedures included the Duhamel procedure, Soave procedure, the Soave Transanal Endorectal Pull-through (TEPT) procedure, and the Swenson TEPT procedure. Early outcomes of the surgery were then compared between males and females. The comparrative analysis was determined based on Chi-square analysis, where p<0.05 was considered significant.
ResultsThere were 111 (61.7%) male patients and 69 (38.3%) female patients, with a mean age of 15.2 months. The Soave TEPT is the most frequently performed procedure (91.7%). Emerging clinical manifestations include constipation (176; 97.8%) and soiling (171; 95%). Preoperative barium enema and postoperative pathological examination confirmed that almost all patients (99.4%) had an aganglionic segment confined to the rectosigmoid area. The average length of operation was 69.7 ± 65 minutes and average bleeding time was 5.4 ± 34 mL. The average discharge time was 3.3 ± 73.3 days. No significant difference was found in post-surgery complications between males and females (p>0.5). The immediate complications were not associated with surgical methods (p = 0.83).
ConclusionOur descriptive study has suggested the Soave TEPT technique as appropriate to manage HD.
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Awareness, Practice and Views of Pediatricians, General Physicians, and Pharmacists about Prescribing Off-label Medication in Pediatric Patients in Eastern Province, Saudi Arabia
BackgroundAn off-label medication involves the use of an approved drug for an unapproved indication, population, route of administration, or dosage.The physiological state of children differs from that of adults, making the adult formulation potentially dangerous to children. Off-label prescribing is quite common in children due to challenges in the development of pediatric formulations. The current study was conducted to determine the awareness, practice, and views of pediatricians, general physicians, and pharmacists about prescribing Off-label medication to pediatric patients in Eastern Province, Saudi Arabia.
MethodsA cross-sectional study based on a questionnaire was conducted among pediatricians, general physicians, and pharmacists (clinical and community) in Eastern Province, Saudi Arabia. Statistical analysis was conducted using the data exported from Google Forms (Mountain View, California, USA) and Microsoft Excel (Version 2016) and then exported into Statistical Package for Social Sciences (SPSS) version 26.0 (IBM, Inc., Armonk, NY, USA). Chi-square was deemed suitable. The level of significance was set at 0.05.
ResultsAmong the study participants, 53(35.09%) were pharmacists, followed by 24(15.89%) others, 22(14.565) pediatricians, 19(12.58%) other specialists, 17(11.25%) general physicians, and 16(10.59%) were clinical pharmacist. About 73(48.34%) described the definition of off-label correctly. About 114(75.49%) believed that parents and guardians must be informed about off-label medicine prescribed to their children. About 52(34.43%) had concerns about the safety of the medication, and 98(64.90%) believed they should be tested in pediatrics during clinical trials. Further, 97(64.23%) considered themselves not enough knowledgeable about off-label medications. The barriers reported by the participants were as follows: 89(58.945%) said lack of information resources, 71(47.01%) said lack of training, 56(37.08%) said lack of information on the safety of excipients used in pediatrics, 47(31.12%) said lack of formulary, 44(29.13%) said lack of guidelines, and 58(5.29%) said lack of information related to the safety of excipient concentration in pediatrics. The proportion of healthcare professionals who agreed that excipients in adult medication may be harmful to pediatrics was 103(68.21%). The drugs most often prescribed as off-label were paracetamol 54(21.68%), followed by Phenobarbital 35(14%), and Amoxicillin 33(13.25%).
ConclusionThere are a considerable number of healthcare professionals unaware of the description of off-label medication. The majority have concerns over the safety and efficacy of the off-label drugs and believe that most frequently used off-label drugs in pediatrics must be tested in pediatrics during clinical trials. In addition, excipient safety data are of considerable importance to ensure off-label drug safety in pediatrics, who believe their knowledge is inadequate and need proper guidelines and training on this issue.
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“Non-COVID-19” Coronavirus Diseases Not to be Misdiagnosed as COVID-19
Authors: Kam L. Hon, Alexander K.C. Leung, Paul K.S. Chan, Su Y. Qian and Kin T. WongBackgroundThe COVID-19 global pandemic was caused by a novel coronavirus (SARS-CoV-2), which then became an endemic infection. COVID refers to the World Health Organization’s coined acronym for coronavirus disease.
Case PresentationWe have, herein, reported three cases of COVIDs that could have been misdiagnosed as COVID-19. All of these families reported previous COVID-19 infection based on self- administered Rapid Antigen Testing (RAT) and completed a period of home isolation. In these 3 cases, one child had an RSV-associated asthma attack, one had norovirus gastritis, and another had an infection with Campylobacter and E. coli. NL63, OC43, and 229E, respectively, were found by PCR in these patients.
DiscussionSeven human coronaviruses cause human infectious diseases. Confusion and issues associated with coronavirus disease diagnosis by Polymerase Chain Reaction (PCR) testing and Rapid Antigen Test (RAT) may arise. Some RATs are Antigen Fluorescent Immunoassays (FIA) that target monoclonal antibodies for the detection of viral nucleocapsid protein. Others target the non-nucleocapsid proteins. False positivity is possible. False negativity is also possible if the specimen’s antigen level is below the test's detection limit. RAT results usually remain positive for 6 to 7 days, but they may stay positive as long as 2 weeks. Stigmatization with the COVID-19 diagnosis may occur. The PCR test is a highly sensitive ‘gold standard’ for the detection of COVID-19, but it can also detect non-infectious individuals’ fragmented non-infectious viral nucleic acids, and could be positive for a long period. An individual may be tested positive for a few weeks to months after the individual becomes non-infectious.
ConclusionThe cases presented here had COVID other than COVID-19, caused by coronavirus variants other than SARS-CoV-2. Co-infections with other pathogens are present in these "Non- COVID-19" COVIDs. PCR testing of non-COVID-19 COVIDs may help in the accurate diagnosis of these ailments and respiratory co-infections.
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Novel Compound Heterozygous Mutations of LIG4 Gene in an Indian LIG4 Syndrome Patient with Severe Microcephaly: Case Report, In-silico Analysis and Systematic Review
Authors: Amit Singh, Sabyasachi Senapati, Inusha Panigrahi and Preeti KhetarpalBackgroundLIG4 syndrome, characterized by immunodeficiency, sensitivity to ionizing radiations, intrauterine growth retardation, postnatal growth retardation, and microcephaly, is a rare genetic disorder caused by pathogenic variants of the LIG4 gene. Few patients are presented with no immune dysregulation as well.
Case StudyWe present here a male child of 2 years and 4 months of age with severe microcephaly and short stature. His birth weight was 1.9 Kg, and his current height, weight, and head circumference are 83.2 cm (z score = -2.37), 9.5 Kg (z score = -2.76), and 36 cm (z score = -9.24), respectively. Possible causative pathogenic compound heterozygous variants of the LIG4 gene, which were inherited from the parents, were identified by whole exome sequencing of the DNA of the patient and his parents. A systematic review of the literature is also performed to summarize the patients of LIG4 syndrome reported worldwide and summarize the associated genetic mutations of the LIG4 gene. Compound heterozygous variants (c.597_600delTCAG/ c.342del) of LIG4 gene were identified. The parents were found to be heterozygous carriers of one variant each.
ConclusionThe in-silico analysis of identified variants explains their effect on the structure and function of the LIG4 protein hence explaining the genotype-phenotype correlation.
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Volumes & issues
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Volume 21 (2025)
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Volume 20 (2024)
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Volume (2024)
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Volume 19 (2023)
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Volume 18 (2022)
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Volume 17 (2021)
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Volume 16 (2020)
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Volume 15 (2019)
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Volume 14 (2018)
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Volume 13 (2017)
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Volume 12 (2016)
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Volume 11 (2015)
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Volume 10 (2014)
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Volume 9 (2013)
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Volume 8 (2012)
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Volume 7 (2011)
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Volume 6 (2010)
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Volume 5 (2009)
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Volume 4 (2008)
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Volume 3 (2007)
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Volume 2 (2006)
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Volume 1 (2005)
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