1,2,4-Oxadiazole Moiety Molecules Synthesis for Cancer

1,2,4-Oxadiazole Moiety Molecules Synthesis for Cancer 2.4. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole derivatives for their MTT assay using MCF-7 breast cancer cell line and degradation of DNA in EAT cells 2.4.1. INTRODUCTION In the biological and pharmacological importance, heterocycles plays a significance role. Oxadiazole molecules show biologically activity includes angiogenesis inhibitor [246] and also HIV inhibitor [247], tyrosine kinase inhibition [45], histamine H3 antagonism [48], muscarinic agonism [49], potent histamine H2 receptor antagonists [50, 51], muscarinic receptor antagonists [53, 54], interleukin-8 (IL-8) receptor antagonists [65], cytotoxic activities [68], monoamine oxidase inhibition [66], potent therapeutic agents for prostate cancer [72], anticonvulsant activity [67], tumor-selective and apoptosis-inducing agents [70, 71], antitumor [4f] and apoptosis-inducing anticancer agents [73, 74]. Breast cancer is a most terrifying disease in which cells in breast tissue grow and divide without normal control. This type of growth of cells without control forms a lump called tumor. In breast cancer, tumors are called benign or malignant. Malignant tumors will grow by eating food. They get the food by forming new blood vessels in a process called angiogenesis. These blood vessels are the main reason to promote the growth of the tumors. After this tumor growing it will spread to nearby tissue, which is called as invasion. The breakage of main tumor cells will spread into other parts of the body and it will lead to metastatic breast cancer. This happens through blood stream or lymphatic system and this process is called metastasis. The main disadvantage of the malignant breast cancer is dividing and grows out of control which leads to form number of new tumors. If those new tumors are in other parts of the body, then also we call those as breast cancer. Especially in women, breast cancer leading to the cause of cancer related death. In developing and developed countries, breast cancer is the second most common malignancy type diagnosed disease in women. In India breast cancer is the most discussing problem in the current health problem (248). By the survey conceded by the Indian Council of Medical Research (ICMR), the percentage of breast cancer patients has been nearly doubled. In the past few years nearly one lakh new patients are being detected from 1985 to 2001 (249, 250). It has been estimated that the breast cancer in 2004 is nearly 90,273 and they predicted that in 2015 the patient’s number may be nearly 1, 12,680 (251). Due to the damage in DNA, normal cells will become cancer cells. DNA is present in every cell and it directs to all its actions. When DNA gets damaged in normal cells, the cell either repairs the damage or it dies. But in the cancer cells, damaged DNA is not repaired. The damaged cell undergoes splitting. As a result cell goes on making new cells that the body doesn’t need and those cells have same damaged DNA as the first cells does. This conjecture the design and synthesis of new anticancer drugs, and drug combination and treatment modalities is still the need for effective treatment of breast cancer patients [252]. 1,2,4-Oxadiazole moiety molecules show signs of vide variety of biological activities [40, 253-255]. In connection to the above studies, our molecules are subjected to the angiogenesis using MCF-7 breast cancer cell lines and degradation of DNA studies using in EAT cells. 2.4.2. MATERIALS Melting points were recorded (uncorrected) on a Buchi Melting Point B-545 instrument. Infrared (IR) spectra were recorded using a Jasco FTIR-4100 series. All reagents and solvents used were commercially procured and used as received. 1H-NMR spectra’s were recorded on Shimadzu AMX-400-Bruker with 400 MHz with TMS as internal standard. The 13C NMR spectra were examined on a Bruker DPX-400 at 100.6 MHz. The mass spectra were recorded on a JEOL JMS-AX505HA mass spectrometer. 2.4.3. EXPERIMENTAL 2.4.3.1. Chemistry General procedure for synthesis of (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2). A solution of hydroxylamine hydrochloride (1.529 g, 22.004 mmol) (2.5eq) and sodium carbonate (1.492 g, 14.082 mmol) (1.6eq) was taken in a round bottom flask. Stir for 10min to dissolve completely, then to this mixture 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile (1) (2.0 g, 8.801 mmol) (1.0 eq) is dissolved with ethanol was added. Then the mixture is heated to 60 0C about 5-6 hr. After that the steps forward of the reaction fusion was examined by the thin layer chromatography (TLC). After reaction completion, the solvent and the product was separated in vacuum pump under reduced pressure. Then the product was poured to water and extracted with ethyl ethanoate. The organic layer was washed 2-3 times with distilled water. The organic layer was washed 2-3 times with distilled water. The extracted ethyl ethanoate layer was dried over sodium sulphate (anhydrous) and the solvent was evaporated to get (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hyd roxybenzimidamide (2). 2.4.3.2. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole 4(a-f) derivatives. (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (1.0 eq) is dissolved in dry dichloromethane and cooled to 0-5 0C in ice bath. Then N,N-diisopropylethylamine (1.1 eq) was added to cold reaction mixture and stirred for 10 minutes, then different aromatic acid chlorides (3a-e) (1 eq) were added. The reaction mixture was allowed to room temperature under stirring for 5-6 hr. After that the steps forward of the reaction fusion was examined by the thin layer chromatography (TLC). After reaction completion, the solvent and the product was separated in vacuum pump under reduced pressure. Then the product was poured to water and extracted with ethyl ethanoate. The organic layer was washed 2-3 times with distilled water. The organic layer was washed 2-3 times with distilled water. The extracted ethyl ethanoate layer was dried over sodium sulphate (anhydrous) and the product was purified with the help of column chromatography over silica gel (60-120 mesh) using hexane and ethyl acetate (1:1). Scheme 1. Reagents and conditions: (i) Sodium carbonate, water, ethanol, 60 0C, 6 h; (ii) dichloromethane, N,N-diisopropylethylamine, 0-5 0C, 6 h; 3(a-e) Where 3a = 4-chloro benzoyl chloride; 3b = 4-Fluoro benzoyl chloride; 3c = 4-(trifluoromethyl)benzoyl chloride; 3d = 4-Fluoro-3-Nitrobenzoyl chloride; 3e = 4-EthylPhenylbenzoyl chloride. 2.4.3.2.1. Synthesis of 5-(4-chlorophenyl)-3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-1,2,4-oxadiazole (4a) Pale yellow color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-chlorobenzoylchloride (3a) (0.067 g, 0.384 mmol) and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.32 (d, 1H, Ar-H), 7.75 (dd, 2H, Ar-H), 7.70, (d, 1H, imid-H), 7.55 (d, 1H, Ar-H), 7.50 (dd, 2H, Ar-H), 7.35 (d, 1H, imid-H), 7.30 (d, 1H, Ar-H), 5.05 (d, 1H, pyrrole-H), 2.56-2.30 (d, 4H, pyrrole-H); MS (ESI) m/z: 381.081 (100.0%), Anal. calcd. for C20H14ClFN4O (in %): C- 63.08, H- 3.71, N- 14.71. 2.4.3.2.2. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(4-fluorophenyl)-1,2,4-oxadiazole (4b) Orange color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-Fluoro benzoyl chloride (3b) (0.060 g, 0.384 mmol)and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.31 (d, 1H, Ar-H), 7.30 (dd, 2H, Ar-H), 7.72, (d, 1H, imid-H), 7.56 (d, 1H, Ar-H), 7.34 (d, 1H, imid-H), 7.31 (d, 1H, Ar-H), 7.29 (dd, 2H, Ar-H), 5.02 (d, 1H, pyrrole-H), 2.58-2.31 (d, 4H, pyrrole-H); MS (ESI) m/z: 365.114 (100.0%), Anal. calcd. for C20H14F2N4O (in %): C- 65.93, H- 3.87, N- 15.38. 2.4.3.2.3. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazole (4c) Dark brown color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-(trifluoromethyl)benzoyl chloride (3c) (0.080 g, 0.384 mmol) and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.33 (d, 1H, Ar-H), 8.10 (dd, 2H, Ar-H), 7.74 (d, 1H, imid-H), 7.70 (dd, 2H, Ar-H), 7.58 (d, 1H, Ar-H), 7.37 (d, 1H, imid-H), 7.33 (d, 1H, Ar-H), 5.06 (d, 1H, pyrrole-H), 2.59-2.29 (d, 4H, pyrrole-H); MS (ESI) m/z: 415.110 (100.0%), Anal. calcd. for C21H14F4N4O (in %): C- 60.87, H- 3.41, N- 13.52. 2.4.3.2.4. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(4-fluoro-3-nitrophenyl)-1,2,4-oxadiazole (4d) Pale yellow color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-Fluoro-3-Nitrobenzoyl chloride (3d) (0.078 g, 0.384 mmol)and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.71 (d, 1H, Ar-H), 8.65 (d, 1H, Ar-H), 8.34 (d, 1H, Ar-H), 7.74 (d, 1H, imid-H), 7.61 (dd, 1H, Ar-H), 7.58 (d, 1H, Ar-H), 7.37 (d, 1H, imid-H), 7.33 (d, 1H, Ar-H), 5.06 (d, 1H, pyrrole-H), 2.59-2.29 (d, 4H, pyrrole-H); MS (ESI) m/z: 410.099 (100.0%), Anal. calcd. for C20H13F2N5O3 (in %): C- 58.68, H- 3.20, N- 13.52. 2.4.3.2.5. Synthesis of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-(5-ethyl-[1,1-biphenyl]-2-yl)-1,2,4-oxadiazole (4e). White color from (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) (0.1 g, 0.384 mmol), 4-EthylPhenylbenzoyl chloride (3e) (0.094 g, 0.384 mmol) and N,N-diisopropylethylamine (0.049 g, 0.461 mmol). 1H NMR (400 MHz, CDCl3): 8.31 (d, 1H, Ar-H), 7.95 (d, 1H, Ar-H), 7.80 (dd, 2H, Ar-H), 7.75 (d, 1H, Ar-H), 7.72, (d, 1H, imid-H), 7.53 (dd, 2H, Ar-H), 7.56 (d, 1H, Ar-H), 7.45 (d, 1H, Ar-H), 7.34 (d, 1H, imid-H), 7.30 (d, 1H, Ar-H), 7.31 (d, 1H, Ar-H), 5.03 (d, 1H, pyrrole-H), 2.65 (q, 2H, -CH2), 2.58-2.31 (d, 4H, pyrrole-H), 1.27 (t, 3H, -CH3),; MS (ESI) m/z: 451.186 (100.0%), Anal. calcd. for C28H23FN4O (in %): C- 74.65, H- 5.15, N- 12.44. 2.4.4. Biology 2.4.4.1. Culture of MCF-7 cells: MCF-7 cells were cultured with minor modification in Minimal Essential medium (Invitrogen) supplemented with 10% fetal bovine serum, 100units/ml penicillin-G, 100  µg/ml streptomycin and 1% sodium bicarbonate (Invitrogen). MCF-7 cells were obtained from Cell repository unit of National Center for Cell Sciences (NCCS), Pune, India. All cell lines were maintained at 37 °C in a humidified atmosphere with 5% CO2 [256]. 2.4.4.2. Culture of EAT cells: Animals, in vivo tumor generation and imidazole derivatives treatment Six to eight weeks old female mice were acclimated for one week while caged in-group of five. Mice were housed and fed a diet of animal chow and water ad libitum throughout the experiment. All the experiments were approved by the institutional animal care and use committee of the University of Mysore, Mysore, India. Ehrlich Ascites Tumor (EAT) cells (5Ãâ€"106 cells/mouse) were injected intraperitoneally. These cells grow in mouse peritoneum forming an ascites tumor with massive abdominal swelling. The animals showed a dramatic increase in body weight over the growth period and the animals succumbed to the tumor burden 14–16 days after implantation. 2.4.4.2.1. Isolation of EAT cells from mice peritoneal cavity and compound treatment: From the peritoneal cavity of tumor-bearing mice the EAT cells were isolated (control and treated). 2-3 mm of sterile PBS was injected in to the peritoneal cavity of the mice and the peritoneal fluid containing tumor cells withdrawn, collect in sterile petri dishes and incubated at 370C for 2 h. The cells of macrophage linage adhered to the bottom of Petri dishes. The non-adherent population was aspirated out gently and washed repeatedly with PBS. Moreover, viability of these cells was assessed and was found to be >95% by trypan blue dye exclusion. The viable EAT cells were processed for further experiments. The EAT cells (5 x 106) were treated with or without compounds of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole series 4(a-e) and incubated at 370 C for different time interval or for known period of time. After the incubation period the cells w ere used for the further analysis [258]. 2.4.4.2.2. Cell count by Trypan blue dye exclusion assay. EAT cells were treated with different concentrations of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole compounds 4(a-e) at various time periods (0–4 h). Cell viability was assessed by mixing aliquots of cell suspension with 0.4% trypan blue and counted using heamocytometer. Cells that picked up the dye were considered to be dead [259(a)]. 2.4.5. Result and Discussion 2.4.5.1. Chemistry Synthesis of the key intermediate (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2) is outlined in Scheme 1. Briefly, hydroxylamine hydrochloride and sodium carbonate was taken in water and stirred. 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile (1) was dissolved in ethanol and added to the reaction mixture. The presence of –NH2 and =N-OH proton peaks NMR spectra indicates the formation of (Z)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-N-hydroxybenzimidamide (2). The key intermediate compound (2) was taken in dry dichloromethane and cooled to 0-5 0C, and N,N-diisopropylethylamine was added. Stirred for 10 min, then different aromatic acid chlorides 3(a-e) was added drop by drop. The reaction mixture was allowed to room temperature under stirring for 5-6 h and after that the steps forward of the reaction fusion was examined by the thin layer chromatography (TLC). After reaction completion, the solvent and th e product was separated in vacuum pump under reduced pressure. Then the product was poured to water and extracted with ethyl ethanoate. The organic layer was washed 2-3 times with distilled water to get target 3-(4-(3-(1H-imidazol-5-yl)propyl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole 4(a-e). Upon completion crude products 4(a-e) were obtained with a good yield of 81–93% and which the product was purified with the help of column chromatography over silica gel (60-120 mesh) using hexane and ethyl acetate (1:1). The absence of –CO proton peak in synthesized derivatives in 1H spectra confirmed the identity of the products. The details of chemical structures, physical data and purity of compounds are given in Table 1. Compound R1 Yield MP (oC) Purity 4a 90 277 90 4b 85 100 93 4c 81 110 89 4d 82 142 92 4e 79 95 81 Table 1. Chemical structures, physical data and purity of compounds 4(a–e) 2.4.5.2. Biology 2.4.5.2.1. MTT assay: The MTT assay was performed according to the protocol previously reported [257]. MCF-7 cells were plated at a density of 1 X 105 cells in 96-well plates. (Subsequently, the 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole series 4(a-e) were assayed using concentrations from 0.05 to 0.5 mM). After 24 h of incubation, 10  µL of 5% 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) (Sigma Aldrich) (0.05 mg/mL) were added to the culture medium. After 4 h at 370C the culture medium was removed and 200  µL of DMSO were added to dissolve the salts of formazan. The absorbance was measured with a 96-wells plate spectrophotometer at 570 nm. The experiments were independently performed three times and each experiment contained triple replicates. Control samples containing a complete culture medium devoid of cells or control cells with 0.1% DMSO were also included in each experiment. Figure 1. The MTT assay of compounds 4(a-e) in MCF-7 breast cancer cell lines. Sl.No. Name of the compound IC50 Value 1 Cisplatin 10ÃŽ ¼g 2 4a 100ug 3 4b 200ug 4 4c 100ug 5 4d 800ug 6 4e 200ug Table 2. Compounds 4(a-e) and their IC50 value ( µg/ml) on MCF-7 breast cancer cell lines. 2.4.5.3. DNA fragmentation assay: EAT cells were collected from mice treated with or without 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazole series 4(a-e). Thein vivo and DNA was isolated using the phenol–chloroform method. In brief, cells were lysed in a buffer containing 50mM Tris–HCl, pH 8.0, and 0.5% SDS, and incubated for 30min at 37 °C. The cell lysate was subjected to 8M potassium acetate precipitation and left for 1h at 4 °C. The supernatant was subjected to phenol/chloroform/isoamyl alcohol (25:24:1) extraction and once to chloroform extraction. DNA was precipitated by adding 1:2 volumes of ice-cold ethanol. The precipitated DNA was dissolved in 50ÃŽ ¼L TE buffer (pH 8.0). The DNA was digested with 20ÃŽ ¼g/mL RNase at 37 °C for 1h. The DNA was quantitated and equal concentration of DNA (25ÃŽ ¼g) was resolved on 1.5% agarose gel, viewed under UV light, and documented using BIORAD gel documentation system Figure 2 [259(b)]. Figure 2. The DNA degradation of compounds 4(a-e) in Ehrlich Ascites Tumor (EAT) cells. Conclusion: A series of 3-(4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorophenyl)-5-substituted-1,2,4-oxadiazoles 4(a-e) has been synthesized by using simple synthetic procedures and were screened for their MTT assay using MCF-7 breast cancer cell line and degradation of DNA in Ehrlich Ascites Tumor (EAT) cells activity. All the final compounds exhibited good in all the in-vitro activity.

Tda 2.2 Safeguarding the Welfare of Children and Young People

Lorraine Bale TDA 2. 2 Safeguarding the welfare of children and young people 1. 1 United Nations convention protection of children’s act- when was the 1st legislation impacted. It was drawn up in 1989, but the United Kingdom decided on 16th December 1991 formally agreed to make sure that every child has the same rights listed in the convention. Signed 20th November 1989 Location New York Effective 2nd September 1990 Condition 20 ratifications Signatories 140 Parties 194 Depositary UN secretary general Languages Arabic, Chinese, English, French, Russian and Spanish The convention generally defines a child as any human being under the age of 18, unless an earlier age of majority is recognised by a countries law. How legislation effect’s our work without children It effects our work as to making sure that all children are treated equally as it’s an obligation to prohibited and eliminate corporals punishment & all other cruel or degrading forms of punishment. Doctors Teachers Social workers Educational staff Speech therapists The children’s act of 2004- Added to and strengthened was raised to clarify the rolls of councils and other agencies in safeguarding & promoting the welfare of children in their area. Section II in the act places a duty on partners such as the primary care trust (PCT) and the police to make legal arrangements to ensure that functions with regards to need to safeguard and promote the welfare of children. It also required all children’s services authorities to establish a local safeguarding children board with legislation guidance published in 006. -Every service plays its part. – The children act 2004 was introduced following high profile enquires into safeguarding children & young people. – The acts aim where to achieve positive outcomes for the children & young people & their families. 1. Improving & integrating children’s service 2. Promoting early intervention 3. Providing strong leadership 4. Bringing together different professionals in multidis ciplinary All agencies working together^ Original children act 1989- Children’s act sets out what local authorities & courts do to protect children In charge- responsibility Local authorities with the duty to investigate if they have reasonable cause to suspect that a child who lives or is found in their area is suffering or is likely to suffer significant harm. Local authorities were also charged with a duty to provide services e. g. schools children in need. Aims 1. To bring together private & public law in one frame work 2. To achieve a better balance between protecting children & enabling parents to challenge state intervention e. . local authorities 3. To encourage greater partnership between statutory authorities & parents 4. To promote the use of voluntary arrangements 5. To restructure the frame work of the courts to facilitate management of family proceedings Lord laming= the laming enquiry is a r eport of under pendent statutory enquiry following the death of Victoria Climbie 1. 2 Work settings- No matter what setting a child is place d in that whole workforce will have some kind of role to play. The workforce will be responsible in making sure that the child is in a safe & happy environment they will need to make sure that the health & safety regulations are in order in making sure the child is a healthy & happy child that the child is not being bullied, put in danger or abused in any way by anybody and if the child is being abused by a parent for them to tell a member of staff they can trust and if its a member of staff to go to the next higher person in charge and then if you feel like nothing is getting done you should contact social services. They are also in charge of making sure that if a child is sick that the child should be removed from where any other child could come in contact and then to contact the child’s parents/carers. G. P- A GP’s role is to see children when they are ill or if they have maybe minor injuries. They will usually check the child and do a diagnosis so if the child has any bruises or cuts or if the child attends the GP quite regularly for similar symptoms they then may think there is something more behind the reason and would then maybe involve another person e. g. social services. Local hospital services- E. g. Accident & emergency units may have children that are brought in for maybe vomiting or injuries on the body the A&E staff may feel these injuries are from something more serious and would then call in social services to look into these problems and then take things further if necessary. 2. 1 Some signs and symptoms of common childhood illnesses are: -Temperature -Runny nose -Sneezing -Vomiting -Diarrhoea -Fever -Aches & pains -Itchy rash -Cough -White spots in mouth -Swollen glands -Cough with whooping sound -Loss of energy . 2 If there are children or young people that are ill or injured you would 1. Check the Childs injury or try to diagnose the illness through symptoms in case they are contagious or life threatening. 2. You would then separate the child from all other children/young people. 3. Then you would inform a senior member of staff who would then take the decision weather to call for medical assistance and parents while the above is going on about the child would need reassuring and comforting. Also make sure the children that were around the accident are reassured. Then if you have the authority you would fill out an accident or medical report. 2. 3 Some of the circumstances when children and young people may require urgent medical attention: -Unconsciousness -Injury to the head -Vomiting -Unable to breath -Broken bones -Allergic reaction -Continuing high temperature -Continuing diarrhoea 2. 4 Fires- First make sure that all children evacuate the building safely always try to close doors & windows but do not leave any children unattended, when safely away from the building then do a role check to double check all children are safe & present. You would then dial 999 and ask for a fire brigade when they respond state in a clear voice that your work setting is on fire giving them the precise address, do not hang up the phone until they have repeated the address to you then stay in a safe place with the children reassuring comfort in them. Security incidents- The first thing you would do would be to check the identity of the person trying to gain access. Refuse access of anyone you are unsure of. If they have a legitimate reason for entering make sure they sign in on the visitor’s record and sign out when they leave. Never leave them alone with any child/young person at any time, unless they have the authority to be left alone. If there is any suspicious behaviour or the person refuses to leave the premises then the police must be called in case it poses any danger to children or staff. Missing children or young people- 1. You would identify the child that is missing 2. You would then find out where the child was last seen 3. You would then conduct a search within the work setting and if unable to locate the child you would then inform a senior of staff and raise the alarm 4. The next step would be to inform the police and parents 5. You would also maybe start an organised search around the local area and parks. 3. 1 Identify the characteristics of different types of child abuse- -Undernourished -Lack of cleanliness -Bruises & cuts/self harm -Clothes that are dirty, have holes and are too small to wear -Uneducated -Constant hunger -Withdrawn -Delayed development -Poor social relationships -Low self esteem -Try to be perfect at everything & then over react when someone criticises them -Lack of medical attention Sexual knowledge that is inappropriate for a child of a young age 3. 2 Describe the risks and possible consequences of children/young people using internet, mobile phones and other technologies- When children/ young people are using the internet unsupervised they could log on to something that is for adults only which means they could be exposed to something they shouldn’t be. They could also be bullied on the internet e. g. social networks o r by texts calls on mobile phones which could eventually cause them to get depressed and harm themselves or even commit suicide. The internet could also out them in danger as they could think they are talking to someone their age but may be a man or women who they may arrange to meet with which could have serious consequences. There are also games which has violent scenes in which could end up hurting someone else thinking its ok as its just a game and could end up getting them into serious trouble. The consequences to these are they could end up: 1. Putting themselves in danger 2. Commiting suicide 3. Seriously hurting someone else . Getting put away/taken away from family 5. Being kidnapped 6. Being sexually abused 3. 3 The actions you would take in response to evidence or concerns that a child/young person has been abused, harmed (self harm) or bullied or maybe at risk of these things. If a child come to you in secrecy to tell you something, you should first never ever promise to keep it a secret or that you wont tell anyone, as this could upset the child who would end up never trusting you or anyone again. As a carer you have to understand the principles of the confidentiality boundaries and know when it is necessary to share them, having to tell someone you would go straight to your line manager who then would take the responsibility or making sure that the child protection policy will then be put in place to protect the child. If you see nothing is done you would then go to your line manager and tell them again and make sure you make notes including days & times in case nothing is done again. If nothing has still not been done about it then go to someone who you could trust, maybe someone who may have higher authority than you. It wouldn’t be good practise to go to social services yourself as you might not know the full story. 3. 4 The actions you would take in response to concerns that a colleague may be failing to comply with safeguarding procedures harming, abusing or bullying a child or young person- If you suspect a member of staff is involved you would talk to another senior member of a staff who works in your setting but if you feel you cant trust them then go to another member of staff you can trust but make sure the information you give is accurate and acted upon e. . if a child is overweight and has a cleanliness issue, and a member of staff won’t interact with them and calls them sarcastic names you would then tell the member of staff who you trust who would then take the appropriate action to having this dealt with by contacting the right safeguarding agency for that issue. 3. 5 The principles and boundaries of confidentiality and when to share them- Confidentiality is very importa nt in safeguarding the children and in doing this you have to follow rules & regulations within the workplace. It is important to understand that if a child or adult tell you something you should only tell the necessary people/person that needs to know. You should never discuss any information about the children outside your setting or to another member of staff unless a need to know basis. Any of the information on the children should always be locked away and only be shown to the appropriate people who need to see e. g. parents, OFSTED, make sure the cupboards are always locked for no one else to see. If anyone who is unauthorised see’s the information, this could cause some serious consequences.

Most Noticeable Gre Essay Portion Samples

Most Noticeable Gre Essay Portion Samples In every one of the 3 body paragraphs of your essay, you should talk about the 3 main parts of the argument that go to demonstrate your point. You won't be requested to write about a particular topic so much as you'll be requested to respond to a particular scenario. As soon as you've gotten your general structure, it's time to be certain that your paragraphs go in logical purchase. One of the absolute most important features about a compelling essay is its capacity to convince the reader by way of sound logical reasoning. Since you may see, the longer the essay, the greater the grades. The grading happens instantaneously, and when you submit your essay, you will get a composite AWA score, together with several metrics on which your essay was graded. Most students believe that essay length the only important aspect in regards to AWA scoring. The fundamental structure of essays is the exact same everywhere, and this site is actually useful in grading your essays. There are quite a lot of sites that can help you in evaluating your essays and also in supplying you with useful GRE sample essays. LiveGrader will also supply you with personalized feedback. To begin with, utilize the perfect-scoring sample GRE essays within this guide as models of potential tactics to do the essay tasks. Or, to actually get a feeling of the way the scores work, have a peek at a couple of sample essays. Nowadays you know what it requires to receive an ideal essay score. The best method to find out how to find a high Analytical Writing score is to examine a GRE essay sample, but doing so with no guidance can be overwhelming. Possessing a few minor errors in your essay is fine, so long as the errors don't help it become impossible to comprehend what you're attempting to say. There are scores and scores of mock essays on the net, and with a very simple google search, you can get access to different essays for the GRE. Simply take a couple of minutes to plan your response and compose an outline before beginning your essay. Take the time to proofread your essay, as soon as you finish writing it. Just because it's possible to determine each thing wrong with the argument doesn't imply that you should do it in your essay. Now, a lot of people don't know the best ways of tackling gre essay topics. To make sure that you will locate a complete answer to every question, we've got a support team that's always online. The Ultimate Gre Essay Portion Samples Trick The first facet of the essay we'll analyze is the way that it succeeds in identifying and examining the sections of the argument that relate to the endeavor. Each paragraph within the body of this perceptive essay identifies and examines an unstated assumption that is essential to the argument. The essays have to be written with respect to the provided instructions. You concentrate on the validity or otherwise of the arguments offered in the essay. At this time you've got to be in a position to understand the differences between both topics you'll be presented with. You are able to then practice replicating successfu l connections between ideas in your practice essays. Just scanning through these 2 lists of essay topics will provide you with a great idea of the kinds of issues and arguments that appear on test day. You must take many different factors into account, if you wish to get anywhere near the ideal score. Gre Essay Portion Samples - What Is It? The writing sample is a far lower priority than GRE prep, therefore we recommend that you jump ahead to the GRE program. The Analytical Writing section of the exam tests your analytical writing and critical thinking skills, though it does not test your understanding of particular content. You may also access your score on the site, once it's been posted. You will get your essay scores approximately 10-15 days following your test date. If you would like to take the GRE General Exam, you will want to prepare an account online, pay the necessary fees and register for the exam you want to take. It's generally clubbed with the verbal section concerning preparation for GRE. Thousands of GRE aspirants visit these forums each day, and if you're able to post your essay and request some feedback, more frequently than not, someone will supply you with the crucial support. Test takers around the world believe they can easily master AWA in a day or two.

Difference Between Organic And Non Organic Products

Introduction On Sunday, October 11, 2015, I visited the weekly Farmer’s Market held on Montrose St. In La Canada California from 9:00am until 2:00pm. This was a smaller Farmer’s Market and took up only one city block. This event was held on a busy street where it was surrounded by restaurants, coffee shops and other small mom and pop shops. My goal was to see the difficulty in distinguishing the difference between organic and non-organic products. Goal Before heading to the local Farmer’s Market, there was one particular detail I was looking for and was hoping to find it on my visit at the market. I noticed that there were many different kinds of organic produce available in different booths. For example, in our supermarket, there are two or three of the same organic product, but with a noticeable price difference, leaving the shopper confused in which to purchase. I was curious to find out, that at the Farmer’s Market, would there be this kind of confusion, or there would be a description or an explanation clarifying the difference between the organic produce. Observation I got to the market at about 11:45am and it was crowded with people spectating and doing their weekly shopping. Many people had baskets or small push carts with items filled in them. As I started walking around, I noticed a wide variety of goods available. Some of the items were produce, nuts, raisins, honey, yogurt and bread. The booths with produce were the busiest ones, so I decided to go and seeShow MoreRelatedOrganic And Non Organic Foods882 Words   |  4 Pagesfood products do you consider purchasing? It is difficult not to notice the current trend of organic foods on the shelves at the supermarket. 1 The word organic refers to the way farmers grow and process agricultural products (Mayo Clinic Staff, par. 3). Whether or not to purchase organic foods has been a subject of debate in recent years. Since in today’s society people are always in search for the healthiest foods available to nurture their bodies. Although few people can tell the difference betweenRead MoreOr ganic Foods Products And Non Organic Products1188 Words   |  5 PagesOrganic products and non-organic products have been a subject of interest for me for a reasonable amount of time because I have often questioned whether there really was a difference between the two types of products chemically. To begin, labeling something as organic you have to very precise and it is determined by the United States Department of Agriculture (USDA). The regulations set are extremely specific and it is relatively difficult to meet the standards. The pesticides must be natural, andRead MoreOrganic Food Is A $29-Billion-Dollar Industry And Is Growing.1582 Words   |  7 PagesOrganic food is a $29-billion-dollar industry and is growing. Organic food is food that are manufactured, processed and handled using only organic means that meets FDA guidelines. Natural food can be labeled freely with very little to no guidelines. While conventional food still has guidelines but not as strict and being ab le to use chemicals and be synthesized themselves. Organic foods also have varying types from, Organic food which is an item that is produced using organic means, with strict standardsRead MoreOrganic Vs Non Organic Vineyards1671 Words   |  7 PagesOrganic vs Non Organic Vineyards There’s many differences between organic vineyards and non-organic vineyards. Organic vineyards, for instance, produce their wine by excluding the use of artificial chemical fertilizers, pesticides, fungicides and herbicides. Non-organic vineyards on the other hand, produce their wine by applying these products. Every year that goes by, our generation is becoming more advanced in the usage of organic products. Many things sold in groceries stores are now availableRead MoreOrganic Vineyards Vs Non Organic Wine1680 Words   |  7 PagesThere are many differences between organic vineyards and non-organic vineyards like for example, organic vineyards produce their wine excluding the use of artificial chemical fertilizers, pesticides, fungicides and herbicides while non-organic vineyards on the other hand do produce their wine applying those products. Every year that passes our generation is becoming more and more advanced in many things, including the usage of organic products. M any things sold at groceries stores are now availableRead MorePolicy Paper : Gmos Are The Problem !1493 Words   |  6 PagesGMOs are the Problem! When grocery shopping, we are faced with the question, â€Å" Do we choose organic or the conventional products?† For some people, this may be an easy question depending on how much you want to spend, or if you choose organic products regardless of the price. However, no matter what an individual chooses, we will always be skeptical of the quality difference in grocery produce. Is organic milk that much different? Is it healthier than the conventional milk in the isle? Will it protectRead MoreOrganic Food And Farming Benefits For Health826 Words   |  4 PagesOrganic Food and Farming Benefits for Health To the casual shopper it may appear that one of the biggest differences between organic and non organic food can be found on the price tag, however, it is important to realize that the true cost of food is not necessarily the price listed on the price tag. Looking more into the quality, how its made and where the food comes from, is beneficial in our choice of the food we pick. Picking organic food have become ever-so popular. Organic food is grown orRead MoreOrganic Food Industry And Marketing Strategies1110 Words   |  5 Pagesfifteen years, organic food industries and companies have grown up tremendously around for its production and marketing strategies. According to the Organic Trade Association’s 2016 Industry Survey, the total organic products sales in 2015 have increased 11% percent from the previous year’s record level hitting a new benchmark of $43.3 billion, and conventional food products accounted for $3.6 billion. The industry saw its largest annual of al l the food sold in the U.S in 2015 was organic was Near toRead MoreFood Choices : Chicken And Apples Essay827 Words   |  4 Pagesthis paper, I will give my findings about non-organic and organic chicken production and also the production of non-organic and organic apples and if chemical fertilizers or pesticides are use in the production of these foods, and how they affect human nutrition, health, and the environment, and lastly some changes I would when buying foods the store after researching. The protein and produce I chose was Chicken and Spinach. Commercial chicken (Non-organic) goes through a process which contains aRead MoreOrganic and Inorganic Food683 Words   |  3 PagesThe Differences Between Organic and Unorganic Food As we know, food is the most important thing in our lives. We can not live without food, it sounds redundant but that is the reality. Imagine if we do not eat any food in a day, we will get very not powere because we do not get the strength that is contained in food. We realized this important thing and now we have found that there are two types of food, organic and unorganic food. Many people still missunderstanding about the definition of organic