SNPs of ABCG2 in Chinese Advanced NSCLC Patients

SNPs of ABCG2 in Chinese Advanced NSCLC Patients Introduction Lung cancer is one of the most prevalent and fatal malignant neoplasm all over the world and non-small-cell lung cancer (NSCLC) accounts for 80%–85% of all lung cancers(1). The majority of NSCLC patients, approximately 80%, presents in locally advanced (phase IIIA/B) or metastatic (phase IV) stages, which results in quite low 5-year survival rates, 8-14.1% for phase IIIA and 1-5% for phase IIIAB/IV (2). The standard treatment of advanced NSCLC, two-drug chemotherapy based on platinum, has reached a bottleneck with limited effect. Tyrosine kinase inhibitors (TKIs), a targeted drug of epidermal growth factor receptor (EGFR), have been recently introduced for the treatment of NSCLC. Clinical trials indicated that Gefitinib and Erlotinib treating advanced NSCLC patients with EGFR mutation could result a remission rate of 62.1%~84.6% and progression-free survival (PFS) of 8.4~13.1 months, which are significantly higher than that in chemotherapy group (32.2%~47.3% and 4.6~6.7 months , respectively), but not over survival(3-6). In order to implement accurate treatment of both chemotherapy and targeted therapy, it’s urgent to find other predictive targets of NSCLC patients to stratify for treatment. ATP binding cassette superfamily G member 2 (ABCG2), also known as breast cancer resistance protein, was demonstrated to be associated with the effect and prognosis of chemotherapy/targeted therapy in NSCLC (7-9). Because the single nucleotide polymorphisms (SNPs) of ABCG2 are supposed to affect the expression of ABCG2 protein and SNPs of ABCG2 in Asian population are different from other ethnicities (10), we conducted this study to evaluate the SNPs of ABCG2 in Chinese advanced NSCLC patients and its association with their prognosis of TKI therapy. Materials and methods Patients and treatment A total of 100 patients with pathology and cytology confirmed advanced or metastatic NSCLC were enrolled into this study between April 2012 and January 2014 in Hangzhou, China. The mutation of EGFR gene was assessable in 32 patients. Other patients were not assessed EGFR mutation. TKI targeted therapy was implemented in 70 NSCLC patients and other therapy was implemented in the other 30 patients. Patients with TKI targeted therapy were treated with Gefitnid (Astrazeneca pharmaceutical co., LTD) at a dose of 250 mg/day or Erlotinib (Roche pharmaceuticals co., LTD) at a dose of 150 mg/day or Icotinib (Zhejiang beida pharmaceutical co., LTD) at a dose of 375 mg/day. The patients’ characteristics were detailed in Table 1. All patients received chest CT every two months after 1 month of therapy. The efficacy of TKI therapy was clarified as complete response (CR), partial response (PR), stable disease (SD) and progression disease (PD) according to RECIST 1.1 [1]. Patients with CR or PR at more than 6 months were considered as responders. Patients with SD and PD at less than 6 months were considered as nonresponders.[A1] Progression-free survival (PFS) was defined as the duration from TKI therapy to disease progression. Overall survival (OS) was defined as the duration from diagnosis to death from any cause. All patients agreed to participate in this study and signed written informed consent. This study was approved by the Institutional Review Board of Nanjing Medical University and performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines[A2]. DNA extraction Blood samples were collected before chemotherapy and kept in a microcentrifuge tubes containing ethylenediamine tetra-acetic acid (EDTA). Genomic DNA was extracted using a DNA purification kit (Flexi Gene DNA Kit, Qiagen, Hilden, Germany). The concentration of genomic DNA was determined with NanoDrop 1000 (Thermo Scientific, Wilmington, USA) and then it was diluted to a standard of 25 ng/ÃŽ ¼l. Analysis of ABCG2 polymorphisms The ABCG2 34 G/A (dbSNP ID: rs2231137), 421 C/A (dbSNP ID: rs 2231142), 1143 C/T (dbSNP ID: rs2622604) and -15622 C/T (dbSNP ID: rs7699188) polymorphisms were amplified by PCR with the appropriate primers. The primers for PCR and single base extension (Table 2) were designed by the Sequenom Assay Designer 3.1 Software (San Diego, CA). The PCR reactions[A3] were performed at 95 °C for 2 min, followed by 40 cycles at 95 °C for 30 s, Tm for 30 s, and 72 °C for 60 s. After PCR amplification, single base extension reaction was performed following the method of Wiltshire et al [2]. Finally, polymorphisms of ABCG2 gene were tested and analyzed using matrix-assisted laser desorption/ionization timeof-flight mass spectrometry (MALDI-TOF MS) and Sequenom MassARRAY system (Sequenom, San Diego, CA, USA). Statistical analysis Allele frequencies of SNPs were calculated and their genotype distributions were assessed using Fisher’s exact test or chi-square test. PFS and OS were evaluated with censored survival time methods and 95% confidence intervals (CI) was obtained from multivariable logistic regression. Kaplan-Meier survival curves were plotted for OS and analyzed with log-rank test. All tests were performed 2-sided and a p-value were carried out using SPSS 18.0 (SPSS Inc., Chicago, IL, USA) software. Results ABCG2 gene polymorphisms The genotyping of ABCG2 34 G/A, 421 C/A, 1143 C/T and -15622 C/T were performed in all these 100 patients. For the ABCG2 34 G/A polymorphism, the frequencies of GG, GA and AA genotypes were 36%, 50% and 14%, respectively. The allele frequencies of G and A were 61% and 39%, respectively. The wide-type ABCG2 421 C/A genotype (CC) had a frequency of 53%, while the CA and AA genotypes were found in 43% and 4% of the patients, respectively. The allele frequencies of G and A were 74.5% and 25.5%, respectively. The frequencies of CC, CT and TT genotypes for ABCG2 1143 C/T were 66%, 29% and 5%, respectively. The allele frequencies of G and A were 80.5% and 19.5%, respectively. Regarding the ABCG2 -15622 C/T polymorphism, the TT genotype was observed in all patients. Therefore, polymorphism of ABCG2 -15622 C/T was not investigated in the following steps. Polymorphisms of ABCG2 and clinical characteristics Patients clinical characteristics were shown in Table 1, and the relationship between polymorphisms of ABCG2 and clinical characteristics were presented in Table 3. No significant correlations were found between ABCG2 polymorphisms (34 G/A, 421 C/A and 1143 C/T) and patients’ characteristics, including gender, age, smoking history, histology and EGFR mutation (p > 0.05). Although there was no significant relationship between ABCG2 421 C/A polymorphism and EGFR mutation, a trend that CA genotype was observed frequently in EGFR mutation positive patients (47.6% in positive patients vs. 18.2% in negative patients, p = 0.119). Then we calculated the allele frequency of A in these patients and a high frequency of allele A in positive patients (33.3% vs. 9.1%, p = 0.038) was observed. Polymorphisms of ABCG2 and clinical outcome of TKI The sensitivity of 70 patients to TKI treatment was shown in Table 4. NO significant correlation was found between ABCG2 polymorphisms (34 G/A, 421 C/A and 1143 C/T) and sensitivity (p > 0.05). As shown in Table 4, median PFS for carriers of the A-allele and GG genotype at position 34 of the ABCG2 gene who were treated with TKI therapy was 8.0 months (95% CI: 5.9-10.1, n = 45) and 6.5 months (95% CI: 4.1-8.9, n = 25), respectively. There was no significant difference in median PFS of NSCLC patients receiving TKI therapy between CC genotype and CA + AA genotype at position 421 of ABCG2 gene (p > 0.05). Median PFS of patients with CC genotype at position 1143 of ABCG2 gene was higher than those with CT and TT genotypes, but no significant difference was found (p > 0.05). The median OS of patients with ABCG2 34 G/A, 421 C/A, 1143 C/T polymorphisms was shown in Table 4. The median OS of patients with GG genotype at position 34 of the ABCG2 gene was 18 months (95% CI: 14.9-21.1, n = 25) and for those with other genotypes (GA and AA) was 31 months (95% CI: 22.9-39.1, n = 45). Figure 1 showed the Kaplan-Meier curve for OS for NSCLC patients receiving TKI therapy in relation to ABCG2 genotypes at 34 G/A (Figure 1A), 421 C/A (Figure 1B) and 1143 C/T (Figure 1C). There was significant difference between patients with GG genotype and those with GA + AA genotypes at position 34 of the ABCG2 gene (p difference between patients that were CC genotype regarding the position 421 of ABCG2 gene and carriers with other genotypes (CA + AA, p > 0.05). No significant difference was found in 1143 C/T polymorphism (p > 0.05). Discussion Our present study observed that three polymorphisms of ABCG2, 34G>A, 421C>A and 1143C>T occured more frequently compared with -15622C>T in Chinese advanced NSCLC patients. As for -15622C>T, all patients presented a TT genotype. Although no relationships were observed between different genotypes of ABCG2 polymorphisms and EGFR status, a higher frequency of allele A (421C>A) in EGFR mutation positive patients was observed. The other polymorphisms were not related to clinical characteristics. The sensitivity and PFS to TKI of 70 patients was not related to polymorphisms. However, the OS of patients with 34G>A mutant type (GA+AA) was significantly longer than those with wild type (GG). The ABCG2 protein is an important member of the ABC transporter superfamily, which has been suggested to be involved in multi-drug resistance (MDR) in cancer. Screening for SNPs in ethnically diverse subjects has identified more than 80 synonymous and nonsynonymous SNPs in the ABCG2 gene to date (12). The two most frequent polymorphisms identified were 34G>A (resulting in V12M) and 421C>A (resulting in a Q141K substitution) transitions (13). A novel diplotype of two polymorphic loci in the ABCG2 promoter involving -15622C>T and 1143C>T were identified recently (14). Introduction of other ABCG2 SNPs can be found in a recent review (15). Despite the similar allele frequency of 421C>A variant among East Asian populations including Chinese (34.2–35.0%) and Japanese (26.6–35.0%), the allele frequency is higher than that of Southeast Asians (15.0%), Middle Easterns (13.0%), Caucasians (8.7–12.0%) and African-Americans (2.3%) (10). Similarly, the allele frequency of the 34G>A variant in Chinese (20.0%), Koreans (19.8%) and Japanese (15.0-19.0%) is comparable. However, it is much lower than that in Southeast Asians (45%) and higher than other ethnic groups including Caucasian (1.7–10.3%), African-American (6.3%) and Middle Eastern (5.0%) populations (10). The allele frequency of 421C>A variant in our studied population was 25.5%, which was comparable to other Asian populations. However, the allele frequency of 34G>A variant was 39.0%, which was higher than other reports from Asian populations. We found that the allele frequency of 1143C>T variant and -15622C>T variant in our study was 19.5% and 100%, respectively. In Caucasians, it was reported to be 22% and 28%, respectively (16). We unexpectedly observed that all the included patients presented TT genotype of -15622C>T. As far as we known, this gene has not been investigated in other Asian populations. Future studies could be conducted to determine the polymorphism of -15622C>T in Asian po pulation and its potential impact. Physiologically, ABCG2 protein is highly expressed in the blood-brain barrier and gastrointestinal tract, where it is thought to play a role in protection against xenobiotic exposure. High ABCG2 expression has also been found in a variety of tumors and correlated with multidrug resistance and poorer clinical outcomes, as this transporter has the ability to extrude its drug substrates out of the cells, thereby decreasing their intracellular accumulation (17, 18)[16]. Primary structural variations of ABCG2 are associated with its drug-transporter function (15). Therefore, SNPs in the ABCG2 gene would influence the pharmacological effects differently in different patients. It has been demonstrated that 421C>A polymorphisms may express low amounts of ABCG2 (19-22) while the influence of 34G>A polymorphisms on ABCG2 expression remains controversial (22, 23). And regarding to 1143C>T and -15622C>T, some researchers found a decreased protein expression related to these two polymorphisms (21 ) and others found no relation between them (24). Moreover, 421C>A polymorphism has been demonstrated to be associated with ATPase activity and drug transport (18). Thus, several clinical studies have investigated the relation between ABCG2 polymorphism and clinical outcome of NSCLC. Mà ¼ller and colleagues (25) found that carriers of the ABCG2 421 A-allele treated with platinum-based drugs showed a significantly worse OS in all lung cancer patients. However, this effect was not statistically significant in the smaller subgroups of SCLC patients or NSCLC patients with platinum-based treatment. They did not found an association between 34G>A polymorphism and prognosis. Another study of 129 unresectable NSCLC cases treated with first-line platinum-based chemotherapy suggested that ABCG2 SNPs rs2725264 and rs4148149 were associated with OS (26). On the other side, there was also evidence showing that ABCG2 polymorphisms were not related to response or prognosis of NSCLC patients treated with gefitinib (24), erlotinib (27) and gemcitabine and/or platinum-based drugs and/or other drugs (28). In our present study, we found the OS of patients with 34G >A mutant type (GA+AA) was significantly longer than those with wild type (GG). However, we did not observe significant differences concerning other polymorphisms including 421C>A, which was found to be associated with prognosis of other cancer by other study (29). Interestingly, it was reported that ABCG2 34 GA/AA genotypes were associated with poor prognosis of Chinese patients with acute leukaemia (30). Polymorphisms of 34G>A seems to have an opposite impact in different types of cancer. The mechanisms are worthy to be investigated in future large studies. Moreover, ABCG2 SNPs was demonstrated not only related to TKI resistance, but also to TKI induced side effects. Cusatis and colleaguesinvestigated associations between allelic variants ofABCG2 with diarrhea and skin toxicity ingefitinib-treated patients. They found that 16 patients heterozygous forABCG2 421C>A developed diarrhea, versus only 13 (12%) of 108 patients homozygous for the wild-type sequence. However, this SNP was not associated with skin toxicity (28). A recent study found that patientscarrying anABCG2 -15622 TT genotype or harboring at least one TT copy in theABCG2 (1143CT, -15622CT) haplotype developed significantly more grade 2/3 diarrhea (23). In our present study, we did not perform the analysis on side effects. However, this is a serious concern which should be taken into consideration in future studies. In Conclusion, Our findings demonstrate a strong association between the ABCG2 34G>A polymorphism and the overall survival of NSCLC patients treated with TKIs, including Gefitnib, Erlotinib and Icotinib. Since these polymorphisms can be assessed with a simple blood test, it might potentially improve the stratification of patients for TKI treatment by identifying genetically high-response subgroups. Therefore, larger prospective trials are warranted to validate these findings. [A3]The PCR reactions were performed in 20 ÃŽ ¼l volumes on 384-well plates (cat. No. TF-0384/W, ABgene, USA) with 20 ng DNA, 10 pmol for each primer and 1 Ãâ€" PCR-Buffer (Sequenom, San Diego, CA, USA). à §Ã‚ ¼Ã‚ ºÃƒ ¤Ã‚ ¸Ã…“à ¨Ã‚ ¥Ã‚ ¿Ãƒ £Ã¢â€š ¬Ã¢â‚¬Å¡

War from Myceneans to Rome Essay -- essays research papers

WAR FROM MYCENEANS TO ROME The modern day soldier did not arrive at the current level of training methods overnight. Throughout history warfare techniques and strategies have evolved from the earliest primitive battles to the latest technologies. The only way to learn about war is to study the past engagements and lessons learned. There are nine principles of war as follows: Objective, Offensive, Mass, Economy of force, Maneuver, Unity of command, Security, Surprise, and Simplicity. These are the areas of study in order to gain a better understanding of what to do and what to avoid during any engagement.   Ã‚  Ã‚  Ã‚  Ã‚  The battles from yesterday differ from those in recent years and today, because the more primitive cultures fought under their leader for food, territory, or the domination of another group. Today’s motives are based more on economic, political, or social reasons regarded as appropriate by a group of individuals instead of the thoughts or intentions of one man.   Ã‚  Ã‚  Ã‚  Ã‚  Mainland Greece is the first study of warfare in the selected readings and by 1600 B.C. a civilization emerged from the Hellas culture and the Minoan culture. This group, known as the Myceneans, fought using chariots and armor made of bronze. By the eighth century B.C., the Myceneans art of war consisted of the phalanx. The phalanx was a solid rectangle of infantrymen carrying armor and spears eight deep. When an army approached another army the phalanxes of both sides would come head to head. The soldiers, who were normally citizens not professional soldiers, would find themselves in the midst of blood and sweat pouring out of the bodies surrounding them from the hand to hand combat. The only way of victory was to hold the lines strong and fight until the other side fled. The problems with this type of formation was that there was no overall leadership within the phalanx, no reserve was established to outflank the opposing army, and there was no way to pursue the fleeing enemy, left them capable to heal and fight another day.   Ã‚  Ã‚  Ã‚  Ã‚  The technique of phalanx had not changed for some time and the Greek warfare stayed the same due to no major opposition force that used different techniques against Greek system. The phalanx was also used because it was a proven technique that had been tested and used successfully. O... ...diterranean, Hannibal moved to engage the Romans and almost conquered them at Cannae (216 B.C.), where the largest Roman army was surrounded, enveloped, and destroyed. The Romans needed military leadership to outwit Hannibal and found it in Scipio.   Ã‚  Ã‚  Ã‚  Ã‚  Scipio made the maniples stronger than ever and increased the amount of horsemen in the cavalry to solve the problem that the Romans had against Hannibal. By using adapting techniques to envelop and control sea power, Scipio was able to defeat Carthage at the battle of Zama (202 B.C.), and thus the Romans were ready to expand their empire from Spain to Asia Minor and from Britain to Northern Africa.   Ã‚  Ã‚  Ã‚  Ã‚   SOURCES USED Preston, Richard A., Alex Roland, and Sydney F. Wise. Men In Arms: A History of Warfare and its interrelationships With Western Society. (Belmont, California:Wadsworth/ Thomson Learning, 2001). Chap 1-3 Warry, John. Warfare in the Classical World: An Illustrated Encyclopedia of Weapons, Warriors, and Warfare in the Ancient Civilisations of Greece and Rome. (Norman, Oklahoma:University of Oklahoma Press, 1995). Chap 1-13

Cycle of poverty Essay

  Explain the critical importance of poverty in affecting outcomes and life chances: Experiencing poverty does not only affect children and young people in the immediate term but also goes onto affect them into adulthood, in other words children and young people do not adapt to this living environment. Poverty shows its damage to Children or young people in different outcomes such as Education & Health. Education – Research tells us that children and young people from poor families are lower down in their levels of education across all stages of the curriculum. A gap of nine months (on average) in learning shows poorer children to be behind that of Children coming from wealthy families when both groups of children are only 3 years of age (the brain is at this age is 80% developed). This gap increases as children remaining in poverty become older when compared to children of the same age that come from more affluent backgrounds. By the age of 11 Children who receive free school meals (sometimes their only meal of the day as children can suffer from malnutrition as a result of poverty) are estimated to be nearly 3 times behind that of children classed as living outside of poverty and alarmingly as the child becomes older the gap in attaining a good level of education increases until they finish secondary school. In addition children from low income families cannot afford to go on school trips they can’t invite friends around for tea. Health – Poverty is linked with increased illnesses e.g. children from wealthier families should not be exposed to damp living conditions. Bad housing causes over-crowded sleeping conditions and along with other factors can have a  mental and physical developmental affect to the child or young person. Premature death is found to be higher as this can have an effect from as early as the unborn baby and goes right into adulthood (professionals live, on average, 8 years longer when compared to unskilled workers). The damage that poverty causes all interlinks, bad housing causing lack of sleep effects concentration levels at school, sickness causes more days from school, social and language skills not built on by not having friends come to tea – home learning, these are only a few examples but still show that they all have an effect on a child or young persons education/development in one way or another. Poor education is linked to un-employment or low income, (this could lead to criminal activity), unemployment/low income is linked to poverty and thus a repeated cycle. 1.3 Analyse a strategic national or local policy that has positive impact on outcomes and life chances for children and young people: The Child Poverty Act obtained Royal Assent on 25 March 2010. This legislation ensures sustained action must be taken to tackle child poverty by this, and future, governments, by the devolved administrations and by local government and their partners. Measuring success The Act sets four challenging UK-wide targets to be met by 2020. These targets are based on the proportion of children living in: relative low income (whether the incomes of the poorest families are keeping pace with the growth of incomes in the economy as a whole) – target is less than ten per cent combined low income and material deprivation (a wider measure of people’s living standards) – target is less than five per cent absolute low income (whether the poorest families are seeing their income rise in real terms) – target is less than five per cent persistent poverty (length of time in poverty) – target is to be set in regulations by 2015 1.4 Explain why strategic direction from national and local policy is required to address factors impacting on outcomes and life chances for children and young people: Strategic direction from national and local policy is required to ensure it reaches every child and young person, by initially completing policy on a national level will allow every factor that has a negative impact on a child’s outcome and is/or detrimental to their life chances to be included as it is has been completed across the nation (taking into  account various reports and completed research projects) and not pockets of areas which may not give the whole picture or areas that need to be addressed – ensuring a more accurate outcome and more detailed information to learn from. All children should be offered the same opportunities. Local policy will be based on national policy but with information relevant to the local area (e.g. contact details, list of professional bodies etc.) Children centres (Sure Start) compare statistics and report them into local government, such as dental hygiene and feed this information back into local government this information can identify the most deprived areas in their county such Staple Hill and Cadbury Heath for South Gloucestershire, the remaining Sure Start centres can then be identified to be located for the most disadvantaged and support and resources concentrated into these centres. 2. Understand how poverty and disadvantage affect children and young people’s development. 2.1 Analyse how poverty and disadvantage may affect children and young people: To touch on points raised under section 1; Physical Development – bad housing and over-crowding can effect a child’s or young person’s physical development in terms of growth, particularly over-crowding in beds. Physical activity is restricted due to the increase of illness or disability – up to 25% increase in comparison to a child not living in poverty. Social and emotional Development – Socially a child or young person can suffer as poverty restricts a child being able to make friends, teasing can occur due to a how a child is dressed and presented. Clothes can smell due to poor living conditions (damp & mould). Behaviour issues such as hyperactivity and impulsivity are also linked to living in poverty, this will affect the ability to make or keep relations with both peers and teachers. Many children are aware of their parent’s financial situation and worry causing them to suffer increased stress levels, due to the child’s awareness of the burden of financial hardship the child is likely to keep these feelings to him/herself. Mental Health issues such as anxiety and depression are 3 to 4 times more likely to occur when again compared to their peers not suffering from living in poverty. These issues in adult hood can result in difficulties in forming relationships or the need to feel accepted can mean the choice to form â€Å"unhealthy† relationship/s. Communication development – This is found to be delayed in children living in poverty – friendships not forming, unable to invite  friends around to their house all aids communication skills without these home learning experiences may contribute to delayed speech development. Parents will have an impact on a child’s communication development. Interaction with parents maybe reduced Intellectual development learning – Research tells us that the cognitive development of a child is greatly reduced when compared to that of a child that is in a warm, loving, authoritive, learning environment. Evidence shows that the brain growth of a child just at the age of 2 is hugely under developed when compared to that of a child that receives these factors. 3. Understand the importance of early intervention for children and young people who are disadvantaged and vulnerable: 3.1 Explain what is meant by both disadvantage and vulnerability: Disadvantage – An unfavourable condition or circumstance or something that places one in an unfavourable condition or circumstance – examples are shown in 1.1 Vulnerability – â€Å"The risk of physical or emotional harm/injury† – again examples of these is show in answer 1.1 3.2 Explain the importance of early intervention for disadvantaged and/or vulnerable children and young people Research tells us that early intervention is crucial in a child’s life, providing the right amount of social and emotional exposure allows a child between the ages of 0-3 years reach their full potential, at the age of 22 months a child’s educational level can be a predicator of their educational achievements at the age of 26 years, thus reducing unemployment and low paid income jobs and therefore better living conditions. This right level of exposure also assists older children in becoming good parents, being good parents and â€Å"what they do† is more important in a child’s early life than wealth, class, education or any other common social factor (leads into providing their child/children with the correct social and emotional exposure. To add to my statement in section 1 – a baby is born with 25% of the brain and by the age of 3 the brain is at 80%, this is a very fast development rate and any bad parenting or neglect can impact a child’s emotional wellbeing into adulthood. Adults found to be â€Å"at risk† when at the age of 3 are found to have 2.5 times more convictions when compared to adults who were not â€Å"at risk† at the same age of 3 , early intervention would reduce this along with improved mental and physical health, teenage  pregnancy, substance abuse and violence – the poverty cycle is being broken. 3.3 Evaluate the impact of early intervention (to follow on from 3.2); Early intervention is crucial as this helps to assist children and their families who need that extra support sometimes in areas – financial as well as socially and emotionally. Providing additional resources (e.g. Health visitors) and financial aid from the government is vital to be able to provide the necessary focus/advice/support groups that can be for children or for the family unit, the range of expertise help goes across the board and has been set up so that help can be offered to suit the child’s/children’s and families own circumstances. Providing early intervention tackles escalating issues that lead into a child’s adult life, e.g. a child with learning difficulties will need support and extra help, without this the child will feel frustrated which will result in behavioural problems, if ignored the cycle will continue and may lead to exclusion/ leaving school early. This will probably have a negative effect on the child’s future, examples of this are drug abuse or seeking employment, the adult may then turn to crime and the result will be prison. Therefore early intervention is crucial as it gives the child the opportunity to meet his full potential and this will allow the child to gain the best possible outcome and life chances. Research also tells us that families with disabled children or complex health needs welcomed early support by professional bodies, this expertise again benefits the child’s wellbeing and future along with the family as a whole. 4. Understand the importance of support and partnership in improving outcomes for young people and children who are experiencing poverty and disadvantage: 4.1 Research the policy and guidance on impacting on support services at national level, and evaluate how this operates at local level: I have researched policies (Graham Allen Review, Children Plan policy and Every Child Matters) and the impact of support services, one policy in particular (the children’s plan policy), the basis of the policy has come from the ECM policy which underpins all policies such as the EYFS framework, Multi agencies working together etc.. The Children Plan policy talks about the  role of parent partnerships in helping to eradicating child poverty by their role in helping their children to reach their full learning potential. This policy is now archived mainly due to the closure of numerous Surestart centres, however whilst completing this assignment I have am aware of the government’s plan to increase family practise nurses – over 4,000. My setting is located on the same premises as a Surestart centre and we are in close contact with the centre often sharing information, so I know the benefits they offer and support it offers to parents/carers, however on reflection the surestart centres are reliant on the â€Å"needing† to visit their centres and this maybe where they fall short, as I would suggest it is the most needing that shy away from attending. I can therefore see how there needs to be balance, a contact FPN (family practice nurse) engaging and visiting families that do access these facilities by visiting their home, the first steps is taken, next by gaining trust, advice can then be given on support within the wider network such as support classes held with the surestart centres. Local government are using the remaining centres to provide availability for the most disadvantaged/vulnerable 2 year olds that will be eligible for the two year old funding with the aim to break the poverty cycle and with the family practice nurses targeting their families from their most deprived areas. This works if the family practise nurse is an expert in her field and the government have provided enough FPN’s to cover the need. 4.2 Explain how carers can be engaged in strategic planning of services: By working together parents and carers can engage in the strategic planning of services with practitioners and other professional’ s. The parent and carer is vital in supporting a child’s development, they are often the child’s first experience and act as the child’s role model in life. Parents/carers can help identify early on any learning needs, this will help to highlight any areas of learning difficulties, by doing this a plan of action (e.g. permission given for additional observations, assessments and meetings) can be agreed upon by all parties which will aid in supporting the child’s development. To assist practitioners and themselves, courses and/or classes are available through support groups, such as SureStart for parents and carers, this will help with understanding the importance of supporting services, this can be areas such as the importance of home learning (up to 70% of the EYFS framework cane par  be learnt/experienced in a supportive home learning environment) and making positive relations between parent/s and their child, again of which will help in the planning and outcome of a child’s development. If circumstances are that thent or carer is under multi-agency involvement the parents can feel over whelmed and anxious so in these situation good relations between parties are vital as this will aid parental co-operation. It is important to note that to make partnerships successful clear and concise communication back to the parent is key, practitioners and multi-agencies should share all relevant information, this can be done in forms of questionnaires, feedback forms, key worker appointment, group meetings etc. CAF (common assessment framework) can help support children, it can identify the correct professional to help with extra support. THE CAF is voluntary, parents/carers can choose to be involved, they also have a say who they would like to help co-ordinate their action plan. This plan will record what is working well for their child/family, signs of progress are the biggest motivator and will show parents/carers the importance of being engaged in the strategic planning processes. 4.3 Analyse how practitioners can encourage carers to support children and young people’s learning and development: Following on from 4.2 – Practitioners can offer encouragement through keyworker meetings, newsletters, being readily approachable, parent’s evenings, information hand-outs, â€Å"WOW† slips and information on the settings website. Practitioners and settings should also be knowledgeable on other professional bodies, know how they can help and what they can offer to carers/parents along with contact details and have the other bodies information leaflets so that they can be given to parents if needed. It is important for settings to be in partnership with parents so that home learning works alongside their learning steps whilst in pre-school, this can be detailed within the child’s learning journal. It is also important to know the child, this knowledge will improve relations with parents forming an element of trust, which should then help the practitioner to guide and encourage the parent and carer to further support their child’s development. 4.4 Explain how interface with adult services is structured so the needs of children and young people whose carers are users of services are taken into account: For example, Surestart centres are structured for the needs of the adults and the children in their care as they are often on  the same grounds or very near local schools and are easily accessible to the community. The adults are able to attend practical courses that often involve their children. They have fabulous resources and stimulating rooms that are centred around children of the early year’s age group. They also have amazing out door areas. The centres are a centre point in providing information help and support to all adults and will contact other professional bodies for the adults if needs be, they also offer courses within their centres. They run groups that cater for adults with children for example, father/male carer and child day, foster carers and toddler groups, parenting classes. 5. Understand the role of the practitioner in supporting children and young people who are vulnerable and experiencing poverty and disadvantage. 5.1 Explain how positive practice with children and young people who are experiencing poverty and disadvantage may increase resilience and self-confidence. Children from a background of poverty or disadvantage may not experience positive interaction whilst at home. This may cause self-confidence issues and/or low self-esteem. Positive interaction from practitioner’s maybe the only positive interaction they receive. Through learning and achievements at pre-school will start to build confidence and a child’s own belief that they can do it and do have the skills and abilities to successfully face and complete challenges. This success will encourage and promote self-belief and may increase a child’s resilience should they suffer negative interaction whilst at home. Positive practice also builds on a child’s social and emotional skills, areas that may be under developed due to poor parenting this self confidence will also lead onto assist in their educational achievements. 5.2 Explain why it is important for practitioners to have high expectations of and ambitions for all children and young people regardless of their background and circumstances. Children and young people regardless of their background should be whilst attending good early year’s settings as it helps promote development and help combat gaps in areas such as social skills. The EPPE report shows that by the time children leave pre-school the developments gaps between their peers (from a wealthier background) evens out as the child starts primary school. High expectations and ambitions allows a practitioner and child ascertain their learning boundaries and a pre-empted low expectation of a child due to background can result in the child not  achieving their full potential. Every child should be given the same opportunities regardless of class or background. 5.3 Analyse how and why practitioners should act as agents and facilitators of change in own work setting. Practitioners acts as agents and facilitators by accepting and understanding the need for change, this can be following partnership with parents/carers, revised and/or new policies that need to be implemented, working with other professional agencies. It can also be done through professional development as a result of peer observations. Policies can either be updated or newly published, these policies are released after research and studies being completed, new policies, such as the Poverty act 2010 or the new EYFS framework will be issued with the best interest of the child and/or families in mind. These changes are therefore necessary to be implemented by the practitioners for the benefit of their keyworker children. Without adjusting or implementing change or practices could be damaging to the child/children. Changes may also be necessary due to interventions with other agencies – such as a CAF report, these changes maybe be individual to the child but found necessary after conclusion made by other professionals. We are continually learning on the best approaches and the support/changes that should be offered to children suffering poverty and vulnerability, if the practitioner is unwilling to make these changes at the first step the child will continue to be deprived of the opportunity to reach their full potential.

Religions Reflection in Architecture - 815 Words

How have architectural styles reflected the philosophies, religions, and politics of various cultures throughout history? I would like to focus my discussion on religions reflection in architecture and hope it will not be too lengthy. Religion forms the foundation of cultural identity and has decisively shaped world civilizations based on differing, but not exclusive, views of ultimate value: mercy and benevolence in Buddhism, morality and ethics in Confucianism, respect in Shintoism, devotion and mystical unity of divine Self in Hinduism, obedience and perseverance in Judaism, love for the Creator and ones fellowman in Christianity, and submission to the will of Allah in Islam. Shrine-like buildings found at Catal Huyuk in†¦show more content†¦The product of two streams of development, one in the Mediterranean and the other in south-central Asia, Muslim architecture is fundamentally centered upon worship. At its heart is the mosque, whose characteristic domes, minarets, and stylized decorative art encouraged contemplation and prayer. After the destruction of the Temple and dispersal of Jews from Israel in 70 C.E., Judaism focused on family ritual and synagogues that housed prayer sanctuaries which faced Jerusalem. By the fifth and sixth centuries, many Arabs respected the non-sexualized symbols of Judaism, its ascetic monotheism, and the Jewish devotion to family life and education. The Arabs called the Jews People of the Book, and Jews and Arabs lived side by side in peace. Resources: Boston College The Art of the Ancient Mediterranean The Worlds First City http://www2.bc.edu/~mcdonadh/course/huyuk.html HistoryWorld History of Buddhist and Hindu Architecture http://www.historyworld.net/wrldhis/PlainTextHistories.asp?historyid=ab96 Teaching Comparative Religion through Art and Architecture Sacred Spaces in Shinto Jinja (Shrine) Shinto University of California, Berkeley http://ias.berkeley.edu/orias/visuals/japan_visuals/shinto.HTM China.Org.Cn The Temple Of Heaven http://www.china.org.cn/english/kuaixun/75120.htm Wikipedia Early Christian Art and Architecture http://en.wikipedia.org/wiki/Early_Christian_art Wikipedia IslamicShow MoreRelatedAncient Architecture : Ancient And Medieval Architecture1015 Words   |  5 PagesReligion’s Architecture Ancient and Medieval Architecture spans from the meaningful Zygurats in Mesopotamia to the elaborate Gothic Churches in France. Architecture has been influenced by many factors like environment, politics, and culture. However, the greater factor that influenced Ancient and Medieval Architecture is religion. Religion, Gods, and the heavens where the key factors in creating Mesopotamian Ziggurats, Egyptian Pyramids, Greek Temples, Christian Basilicas, Islamic Mosques, andRead MoreThe Islamic Center Of Akron / Kent Essay2276 Words   |  10 PagesMuslim and at the center to pray, I would feel awakened and alert to what was ahead. Interestingly, this action was not foreign to me; during the High Holidays in Judaism, the Shofar is blown and serves as a â€Å"wake up† call to Jews to begin their reflections and pleas for forgiveness of their sins. Finally, as we entered the prayer hall we were invited to sit and observe. Everyone present to pray sat with purpose as they faced the direction of Mecca and ready to receive the message. What many do notRead MoreGp Essay Mainpoints24643 Words   |  99 Pagesdedicated to anti-racism, Jewish culture, war museums etc. †¢ Forbidden fruit effect †¢ A critical analysis on the media will inspire youths to question why violence is so prevalent in our media today †¢ Help them to realize that media is not a reflection of reality but rather a social construct †¢ White House report that media literacy empowers young people, not only to understand and evaluate the ideas found in popular culture, but also â€Å"to be positive contributors to society, to challenge cynicism