Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
2.
Plast Reconstr Surg ; 150(3): 496e-505e, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35749222

RESUMO

BACKGROUND: Women with breast cancer-related genetic pathogenic variants (e.g., BRCA1 , BRCA2 ) or with a strong family history carry lifetime risks of developing breast cancer of up to 80 to 90 percent. A significant proportion of these women proceed to bilateral risk-reducing mastectomy. The authors aimed to document the surgical morbidity of risk-reducing mastectomy and establish whether a diagnosis of breast cancer at the time of surgery impacted outcomes. METHODS: Clinical details of 445 women identified as having a greater than 25 percent lifetime risk of developing breast cancer who underwent risk-reducing mastectomy and breast reconstruction were interrogated for surgical outcomes such as planned, unplanned, and emergency procedures; complication rates; length of stay; and longevity of breast reconstruction. These outcome measures were recorded in women diagnosed with breast cancer perioperatively (cancer group) and those without malignancy (benign group). RESULTS: Median follow-up was similar in both groups (benign group, 70 months; cancer group, 73 months). Patients were older in the cancer group than in the benign group (43 years versus 39 years; p < 0.001). Women in the cancer group required more planned procedures to complete reconstruction than those in the benign group (four versus two; p = 0.002). Emergency procedures, unplanned surgical interventions (e.g., capsulectomy), and postreconstruction complication rates were similar between groups. One in five women overall required revision surgery. Patients with autologous reconstructions had a revision rate of 1.24 per 1000 person-years compared with 2.52 per 1000 person-years in the implant reconstruction group. CONCLUSIONS: Women contemplating risk-reducing mastectomy can be reassured that this is a safe and effective procedure but will likely take multiple interventions. This knowledge should be integral to obtaining informed consent. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.


Assuntos
Neoplasias da Mama , Mamoplastia , Neoplasias da Mama/patologia , Feminino , Humanos , Mamoplastia/métodos , Mastectomia/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Resultado do Tratamento
3.
J Genet Couns ; 31(4): 922-936, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35194886

RESUMO

Genetic services are rapidly growing in the Arab world leading to increasing number of patients being diagnosed with genetic disorders. Islam is the only/major religion of the local population in these countries. Muslim patients integrate religion in virtually every aspect of their lives, and it is vital to understand the role of Islam on their coping and decision-making in the context of genetic counseling. This will help provide patients with the most appropriate services aligned to their religious beliefs and will improve outcomes. Increasing numbers of patients are being diagnosed with Long QT syndrome in Saudi Arabia. Using semi-structured interviews, this study explored the role of Islam on the lived experience of 13 Saudi participants diagnosed with autosomal dominant Long QT syndrome (3/13) or who are carriers of Jervell and Lange-Nielsen syndrome (10/13). The interviews investigated how they made sense of living with the condition in light of their religion/spirituality. The data were analyzed using interpretative phenomenological analysis and produced four superordinate themes: 1) Common belief and idiosyncratic interpretation; 2) Using religion to justify positive reframing of current illnesses; 3) Interplay between belief in medicine and in religion; and 4) Complex impact of diagnosis on religiosity. The results show that the participants' idiosyncratic interpretations of the religious principles, not the principles themselves, had an important influence on their coping, medical decision-making, perceptions regarding the cause of their disease, and compliance with medical advice. A novel insight of the current study is that the personal understanding and interpretation of medical information played the greatest role in the decision-making process, and not the religious beliefs. Thus, it is important for health professionals to give patients' information in a manner that is clear and detailed in order for them to facilitate an informed decision, and to ensure that they fully understand the implications.


Assuntos
Islamismo , Síndrome do QT Longo , Adaptação Psicológica , Humanos , Arábia Saudita
4.
J Med Genet ; 59(4): 328-334, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33452216

RESUMO

BACKGROUND: Testing cancers for mismatch repair deficiency (dMMR) by immunohistochemistry (IHC) is a quick and inexpensive means of triaging individuals for germline Lynch syndrome testing. The aim of this study was to evaluate tumour dMMR and the prevalence of Lynch syndrome in patients referred to the Manchester Centre for Genomic Medicine, which serves a population of 5.6 million. METHODS: Tumour testing used IHC for MMR proteins with targeted BRAF and MLH1 promotor methylation testing followed by germline mutation and somatic testing as appropriate. RESULTS: In total, 3694 index tumours were tested by IHC (2204 colorectal cancers (CRCs), 739 endometrial cancers (ECs) and 761 other), of which 672/3694 (18.2%) had protein loss, including 348 (9.4%) with MLH1 loss. MLH1 loss was significantly higher for 739 ECs (15%) vs 2204 CRCs (10%) (p=0.0003) and was explained entirely by higher rates of somatic MLH1 promoter hypermethylation (87% vs 41%, p<0.0001). Overall, 65/134 (48.5%) patients with MLH1 loss and no MLH1 hypermethylation or BRAF c.1799T>A had constitutional MLH1 pathogenic variants. Of 456 patients with tumours showing loss of MSH2/MSH6, 216 (47.3%) had germline pathogenic variants in either gene. Isolated PMS2 loss was most suggestive of a germline MMR variant in 19/26 (73%). Of those with no germline pathogenic variant, somatic testing identified likely causal variants in 34/48 (71%) with MLH1 loss and in MSH2/MSH6 in 40/47 (85%) with MSH2/MSH6 loss. CONCLUSIONS: Reflex testing of EC/CRC leads to uncertain diagnoses in many individuals with dMMR following IHC but without germline pathogenic variants or MLH1 hypermethylation. Tumour mutation testing is effective at decreasing this by identifying somatic dMMR in >75% of cases.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Neoplasias do Endométrio , Neoplasias Encefálicas , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Metilação de DNA/genética , Reparo de Erro de Pareamento de DNA/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Mutação em Linhagem Germinativa/genética , Humanos , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Síndromes Neoplásicas Hereditárias , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo
5.
Eur J Hum Genet ; 30(4): 413-419, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34866136

RESUMO

It is 30 years since the first diagnostic cancer predisposition gene (CPG) test in the Manchester Centre for Genomic Medicine (MCGM), providing opportunities for cancer prevention, early detection and targeted treatments in index cases and at-risk family members. Here, we present time trends (1990-2020) of identification of index cases with a germline CPG variant and numbers of subsequent cascade tests, for 15 high-risk breast and gastro-intestinal tract cancer-associated CPGs: BRCA1, BRCA2, PALB2, PTEN, TP53, APC, BMPR1a, CDH1, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11 and MUTYH. We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n = 1999) and the mismatch repair CPGs associated with Lynch Syndrome (n = 731). These data are important for service provision and health economic assessment of CPG diagnostic testing, in terms of cancer prevention and early detection strategies, and identifying those likely to benefit from targeted treatment strategies.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Mutação em Linhagem Germinativa , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Genes BRCA2 , Predisposição Genética para Doença , Humanos
6.
Breast ; 60: 45-52, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34464846

RESUMO

BACKGROUND: Bilateral-Risk-Reducing-Mastectomy-(BRRM) is well described in BRCA1/2 pathogenic variant carriers. However, little is known about the relative uptake, time trends or factors influencing uptake in those at increased breast cancer risk not known to be carriers. The aim of this study is to assess these factors in both groups. METHODS: BRRM uptake was assessed from entry to the Manchester Family History Clinic or from date of personal BRCA1/2 test. Follow up was censored at BRRM, breast cancer diagnosis, death or January 01, 2020. Cumulative incidence and cause specific and competing risk regression analyses were used to assess the significance of factors associated with BRRM. RESULTS: Of 7195 women at ≥25% lifetime breast cancer risk followed for up to 32 years, 451 (6.2%) underwent pre-symptomatic BRRM. Of those eligible in different risk groups the 20-year uptake of BRRM was 47.7%-(95%CI = 42.4-53.2%) in 479 BRCA1/2 carriers; 9.0% (95%CI = 7.26-11.24%) in 1261 women at ≥40% lifetime risk (non-BRCA), 4.8%-(95%CI = 3.98-5.73%) in 3561 women at 30-39% risk and 2.9%-(95%CI = 2.09-4.09%) in 1783 women at 25-29% lifetime risk. In cause-specific Cox regression analysis death of a sister with breast cancer<50 (OR = 2.4; 95%CI = 1.7-3.4), mother<60 (OR = 1.9; 95%CI = 1.5-2.3), having children (OR = 1.4; 95%CI = 1.1-1.8), breast biopsy (OR = 1.4; 95%CI = 1.0-1.8) were all independently associated with BRRM uptake, while being older at assessment was less likely to be associated with BRRM (>50; OR = 0.26,95%CI = 0.17-0.41). Uptake continued to rise to 20 years from initial risk assessment. CONCLUSION: We have identified several additional factors that correlate with BRRM uptake and demonstrate continued increases over time. These factors will help to tailor counselling and support for women.


Assuntos
Neoplasias da Mama , Mastectomia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Criança , Feminino , Heterozigoto , Humanos , Incidência , Mutação , Medição de Risco
7.
J Med Genet ; 58(10): 687-691, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-32917768

RESUMO

BACKGROUND: Hereditary causes of ovarian cancer include Lynch syndrome, which is due to inherited pathogenic variants affecting one of the four mismatch repair genes involved in DNA repair. The aim of this study was to evaluate tumour mismatch repair deficiency and prevalence of Lynch syndrome in high-risk women referred to the Manchester Centre for Genomic Medicine with ovarian cancer over the past 20 years. METHODS: Women with ovarian cancer diagnosed before the age of 35 years and/or with a suggestive personal or family history of Lynch syndrome cancers underwent tumour testing with immunohistochemistry for mismatch repair deficiency and, where indicated, MLH1 promoter methylation testing followed by constitutional testing for Lynch syndrome. RESULTS: In total, 261 ovarian cancers were tested and 27 (10.3%; 95% CI 6.9% to 14.7%) showed mismatch repair deficiency by immunohistochemistry. Three of 7 with MLH1 loss showed MLH1 promoter hypermethylation, and 18 of the remaining 24 underwent constitutional testing for Lynch syndrome. A further 15 women with mismatch repair proficient tumours underwent constitutional testing because of a strong family history of Lynch syndrome cancers. Pathogenic variants were identified in 9/33 (27%) women who underwent constitutional testing, aged 33-59 years (median 48 years), including one whose tumour was mismatch repair proficient. Most Lynch syndrome tumours were of endometrioid histological subtype. CONCLUSIONS: Tumour mismatch repair deficiency identified by immunohistochemistry is a useful prescreen for constitutional testing in women with ovarian cancer with personal or family histories suggestive of Lynch syndrome.


Assuntos
Reparo de Erro de Pareamento de DNA/genética , Predisposição Genética para Doença , Neoplasias Ovarianas/etiologia , Adulto , Alelos , Dano ao DNA , Metilação de DNA , Feminino , Estudos de Associação Genética , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Instabilidade de Microssatélites , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Mutação , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo , Deleção de Sequência , Adulto Jovem
8.
Eur J Hum Genet ; 28(11): 1541-1547, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32651552

RESUMO

Poly(ADP-ribose) polymerase (PARP) inhibitors improve survival in BRCA-mutant high-grade serous ovarian carcinoma. As a result, germline and somatic BRCA1/2 testing has become standard practice in women diagnosed with ovarian cancer. We outline changes in testing and detection rates of germline BRCA1/2 pathogenic variants (PVs) in cases of non-mucinous epithelial ovarian cancer diagnosed during three eras, spanning 12 years, within the North West of England, and compare the uptake of cascade testing in families identified by oncology-led mainstreaming versus regional genetics clinics. Eras included: Period 1 (20% risk threshold for testing): between January 2007 and May 2013; Period 2 (10% risk threshold for testing): between June 2013 and October 2017 and; Period 3 (mainstream testing): between November 2017 and November 2019. A total of 1081 women underwent germline BRCA1/2 testing between January 2007 and November 2019 and 222 (20.5%) were found to have a PV. The monthly testing rate increased by 3.3-fold and 2.5-fold between Periods 1-2 and Periods 2-3, respectively. A similar incidence of germline BRCA1/2 PVs were detected in Period 2 (17.2%) and Period 3 (18.5%). Uptake of cascade testing from first-degree relatives was significantly lower in those women undergoing mainstream testing compared with those tested in regional genetics clinics (31.6% versus 47.3%, P = 0.038). Mainstream testing allows timely detection of germline BRCA1/2 status to select patients for PARP inhibitors, but shortfalls in the uptake of cascade testing in first-degree relatives requires optimisation to broaden benefits within families.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/genética , Testes Genéticos/métodos , Neoplasias Ovarianas/genética , Adulto , Idoso , Carcinoma Epitelial do Ovário/diagnóstico , Inglaterra , Feminino , Testes Genéticos/normas , Testes Genéticos/estatística & dados numéricos , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico
9.
World J Gastrointest Oncol ; 11(2): 102-116, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30788038

RESUMO

BACKGROUND: Identification of germ-line mutations in pancreatic ductal adenocarcinoma (PDAC) could impact on patient/family. AIM: To assess the referral pathways for genetic consultations in PDAC. METHODS: Electronic records of PDAC patients were reviewed retrospectively. Patients eligible for genetic consultation referral were identified following the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) criteria. RESULTS: Four-hundred patients were eligible. Of 113 patients (28.3%) meeting EUROPAC criteria, 8.8% were referred for genetic opinion. Germ-line mutations were identified in 0.75% of the whole population. CONCLUSION: Earlier referrals and increased awareness may be able to overcome the low rate of successful genetic appointments.

10.
J Med Genet ; 54(10): 674-681, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28490612

RESUMO

BACKGROUND: While the requirement for thresholds for testing for mutations in BRCA1/2 is being questioned, they are likely to remain for individuals unaffected by a relevant cancer. It is still useful to provide pretesting likelihoods, but models need to take into account tumour pathology. METHODS: The Manchester Scoring System (MSS) is a well-used, simple, paper-based model for assessing carrier probability that already incorporates pathology data. We have used mutation testing data from 4115 unrelated samples from affected non-Jewish individuals alongside tumour pathology to further refine the scoring system. RESULTS: Adding additional points for high-grade serous ovarian cancer <60 (HGSOC=+2) and adding grade score to those with triple-negative breast cancer, while reducing the score for those with HER2+ breast cancer (-6), resulted in significantly improved sensitivity and minor improvements in specificity to the MSS. Sporadic HGSOC <60 years thus reached a score of 15-19 points within the 10% grouping consistent with the 15/113-13.2% that were identified with a BRCA1/2 pathogenic variant. Validation in a population series of ovarian cancer from Cambridge showed high sensitivity at the 10% threshold 15/17 (88.2%). CONCLUSIONS: The new pathology-adjusted Manchester score MSS3 appears to provide an effective and simple-to-use estimate of the 10% and 20% thresholds for BRCA1/2 likelihood. For unaffected individuals, the 20-point (20%) threshold in their affected first-degree relative can be used to determine eligibility at the 10% threshold.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Testes Genéticos , Neoplasias Ovarianas/genética , Neoplasias da Mama/patologia , Feminino , Predisposição Genética para Doença , Humanos , Mutação , Gradação de Tumores , Neoplasias Ovarianas/patologia , Medição de Risco , Sensibilidade e Especificidade
12.
J Hazard Mater ; 300: 522-529, 2015 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-26247378

RESUMO

Cement stabilization of arsenic-bearing wastes is recommended to limit arsenic release from wastes following disposal. Such stabilization has been demonstrated to reduce the arsenic concentration in the Toxicity Characteristic Leaching Procedure (TCLP), which regulates landfill disposal of arsenic waste. However, few studies have evaluated leaching from actual wastes under conditions similar to ultimate disposal environments. In this study, land disposal in areas where flooding is likely was simulated to test arsenic release from cement stabilized arsenic-bearing iron oxide wastes. After 406 days submersed in chemically simulated rainwater, <0.4% of total arsenic was leached, which was comparable to the amount leached during the TCLP (<0.3%). Short-term (18 h) modified TCLP tests (pH 3-12) found that cement stabilization lowered arsenic leaching at high pH, but increased leaching at pH<4.2 compared to non-stabilized wastes. Presenting the first characterization of cement stabilized waste using µXRF, these results revealed the majority of arsenic in cement stabilized waste remained associated with iron. This distribution of arsenic differed from previous observations of calcium-arsenic solid phases when arsenic salts were stabilized with cement, illustrating that the initial waste form influences the stabilized form. Overall, cement stabilization is effective for arsenic-bearing wastes when acidic conditions can be avoided.


Assuntos
Arsênio/análise , Materiais de Construção , Água Potável/análise , Resíduos Industriais/análise , Ferro/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Concentração de Íons de Hidrogênio , Hidróxido de Sódio/química , Solubilidade , Instalações de Eliminação de Resíduos
13.
J Med Genet ; 52(8): 553-6, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26101330

RESUMO

INTRODUCTION: Lynch syndrome is known to cause an increased risk of malignancies, including bowel and endometrial cancers. However, the risk of breast cancer associated with mutations in the mismatch repair (MMR) genes that cause Lynch syndrome is still unclear. MATERIALS AND METHODS: This study assesses the cumulative risk of breast cancer in 106 MLH1 and 118 MSH2 families. Families were referred on the basis of clinical criteria. Pedigree information was obtained, and tumour immunohistochemistry and microsatellite testing performed. Appropriate patients underwent sequencing and multiple ligation dependent probe amplification of all relevant exons of the MMR genes. Kaplan-Meier analysis of cumulative lifetime risk of breast cancer was made combining proven mutation carriers and their first-degree female relatives. RESULTS: After allocation of mutation status, the cumulative risk of breast cancer to 70 years in MLH1 carriers was 18.6% (95% CI 11.3 to 25.9)). This is significantly higher than the cumulative risk for MSH2 which was 11.2% (95% CI 1.4 to 21.0) to age 70 years (p=0.014). The UK population risk is 7.5%-8% at the age of 70 years. Prospective analysis identified six breast cancers in 1120 years of follow-up with an OR of 3.41 (95% CI 1.53 to 7.59). DISCUSSIONS: Female MLH1 carriers would appear to be at moderate risk of breast cancer and should be considered for breast screening at ages earlier than national screening programmes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias da Mama/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Proteínas Nucleares/genética , Adolescente , Adulto , Idoso , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Feminino , Estudos de Associação Genética , Heterozigoto , Humanos , Incidência , Estimativa de Kaplan-Meier , Repetições de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Linhagem , Medição de Risco
14.
Fam Cancer ; 14(1): 51-60, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25342222

RESUMO

Women with Lynch syndrome (LS) have a significantly increased lifetime risk of endometrial cancer (40-60 %) and ovarian cancer (7-12 %). Currently there is little evidence to support the efficacy of screening for the early detection of these cancers. Another option is risk-reducing hysterectomy and/or bilateral salpingo-oophorectomy (BSO). Research on the impact of BSO in premenopausal women with a non-LS associated family history cancer has generally shown that women have a high level of satisfaction about their decision to undergo surgery. However, debilitating menopausal symptoms and sexual dysfunction are common post-surgical problems. We used a mixed methods study to explore the impact of risk-reducing gynaecological surgery in women with LS: 24 women were invited to take part; 15 (62.5 %) completed validated questionnaires and 12 (50 %) participated in semi-structured interviews. Our results suggest that risk reducing surgery does not lead to significant psychological distress and the women tend not to think or worry much about developing cancer. However, they tend to be distressed about the physical and somatic symptoms associated with menopause; their social well-being is somewhat affected, but sexual difficulties are minimal. The women reported being overwhelmingly satisfied with their decision to have surgery and with the quality of information they received prior to the operation. However, they felt underprepared for menopausal symptoms and received conflicting advice about whether or not to use HRT. Recommendations from the study include that professionals discuss the menopause, its side effects and HRT in detail prior to surgery.


Assuntos
Neoplasias do Endométrio/prevenção & controle , Histerectomia/psicologia , Neoplasias Ovarianas/prevenção & controle , Ovariectomia/psicologia , Procedimentos Cirúrgicos Profiláticos/psicologia , Salpingectomia/psicologia , Adulto , Neoplasias do Endométrio/genética , Estudos de Avaliação como Assunto , Feminino , Predisposição Genética para Doença , Humanos , Histerectomia/efeitos adversos , Entrevistas como Assunto , Síndrome de Lynch II/complicações , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Ovariectomia/efeitos adversos , Satisfação do Paciente , Pré-Menopausa , Procedimentos Cirúrgicos Profiláticos/efeitos adversos , Salpingectomia/efeitos adversos , Inquéritos e Questionários
15.
Environ Sci Technol ; 48(7): 4038-47, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24625288

RESUMO

The impact of monochloramine disinfection on the complex bacterial community structure in drinking water systems was investigated using culture-dependent and culture-independent methods. Changes in viable bacterial diversity were monitored using culture-independent methods that distinguish between live and dead cells based on membrane integrity, providing a highly conservative measure of viability. Samples were collected from lab-scale and full-scale drinking water filters exposed to monochloramine for a range of contact times. Culture-independent detection of live cells was based on propidium monoazide (PMA) treatment to selectively remove DNA from membrane-compromised cells. Quantitative PCR (qPCR) and pyrosequencing of 16S rRNA genes was used to quantify the DNA of live bacteria and characterize the bacterial communities, respectively. The inactivation rate determined by the culture-independent PMA-qPCR method (1.5-log removal at 664 mg·min/L) was lower than the inactivation rate measured by the culture-based methods (4-log removal at 66 mg·min/L). Moreover, drastic changes in the live bacterial community structure were detected during monochloramine disinfection using PMA-pyrosequencing, while the community structure appeared to remain stable when pyrosequencing was performed on samples that were not subject to PMA treatment. Genera that increased in relative abundance during monochloramine treatment include Legionella, Escherichia, and Geobacter in the lab-scale system and Mycobacterium, Sphingomonas, and Coxiella in the full-scale system. These results demonstrate that bacterial populations in drinking water exhibit differential resistance to monochloramine, and that the disinfection process selects for resistant bacterial populations.


Assuntos
Bactérias/efeitos dos fármacos , Cloraminas/toxicidade , Desinfecção/métodos , Água Potável/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Azidas/toxicidade , Bactérias/genética , Cinética , Viabilidade Microbiana/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Microbiota/genética , Filogenia , Análise de Componente Principal , Propídio/análogos & derivados , Propídio/toxicidade , RNA Ribossômico 16S/genética
16.
Environ Sci Technol ; 47(19): 10799-812, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24004144

RESUMO

Water treatment technologies for arsenic removal from groundwater have been extensively studied due to widespread arsenic contamination of drinking water sources. Central to the successful application of arsenic water treatment systems is the consideration of appropriate disposal methods for arsenic-bearing wastes generated during treatment. However, specific recommendations for arsenic waste disposal are often lacking or mentioned as an area for future research and the proper disposal and stabilization of arsenic-bearing waste remains a barrier to the successful implementation of arsenic removal technologies. This review summarizes current disposal options for arsenic-bearing wastes, including landfilling, stabilization, cow dung mixing, passive aeration, pond disposal, and soil disposal. The findings from studies that simulate these disposal conditions are included and compared to results from shorter, regulatory tests. In many instances, short-term leaching tests do not adequately address the range of conditions encountered in disposal environments. Future research directions are highlighted and include establishing regulatory test conditions that align with actual disposal conditions and evaluating nonlandfill disposal options for developing countries.


Assuntos
Arsênio , Eliminação de Resíduos/métodos , Purificação da Água , Arsênio/análise , Poluentes Ambientais/análise , Resíduos Sólidos/análise
17.
Environ Sci Technol ; 46(21): 11702-9, 2012 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-23030510

RESUMO

Terminal electron accepting process (TEAP) zones developed when a simulated groundwater containing dissolved oxygen (DO), nitrate, arsenate, and sulfate was treated in a fixed-bed bioreactor system consisting of two reactors (reactors A and B) in series. When the reactors were operated with an empty bed contact time (EBCT) of 20 min each, DO-, nitrate-, sulfate-, and arsenate-reducing TEAP zones were located within reactor A. As a consequence, sulfate reduction and subsequent arsenic removal through arsenic sulfide precipitation and/or arsenic adsorption on or coprecipitation with iron sulfides occurred in reactor A. This resulted in the removal of arsenic-laden solids during backwashing of reactor A. To minimize this by shifting the sulfate-reducing zone to reactor B, the EBCT of reactor A was sequentially lowered from 20 min to 15, 10, and 7 min. While 50 mg/L (0.81 mM) nitrate was completely removed at all EBCTs, more than 90% of 300 µg/L (4 µM) arsenic was removed with the total EBCT as low as 27 min. Sulfate- and arsenate-reducing bacteria were identified throughout the system through clone libraries and quantitative PCR targeting the 16S rRNA, dissimilatory (bi)sulfite reductase (dsrAB), and dissimilatory arsenate reductase (arrA) genes. Results of reverse transcriptase (RT) qPCR of partial dsrAB (i.e., dsrA) and arrA transcripts corresponded with system performance. The RT qPCR results indicated colocation of sulfate- and arsenate-reducing activities, in the presence of iron(II), suggesting their importance in arsenic removal.


Assuntos
Arsênio/metabolismo , Reatores Biológicos , Poluentes Químicos da Água/metabolismo , Purificação da Água/métodos , Arseniatos/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Elétrons , Genes Bacterianos/genética , Filogenia , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sulfatos/metabolismo
18.
J Med Genet ; 49(4): 264-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22362873

RESUMO

BACKGROUND: Neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), familial adenomatous polyposis (FAP), von Hippel-Lindau syndrome (VHL), and Gorlin syndrome (GS) are single gene diseases that predispose to early onset tumours. Few studies have assessed the effect of these diseases on life expectancy. This study's aim was to assess this effect, and to test the hypothesis that genetic registers increase survival. METHOD: NF1, NF2, VHL, FAP, and GS patients were identified through the North West Regional Genetic Register Service and the North West Cancer Intelligence Service. Information on benign and malignant tumours, and deaths were obtained. Kaplan-Meier curves were used to show actuarial survival rates for each disease, compared to the local population, and in patients diagnosed pre/post the regional genetic register. Log rank (Mantel-Cox) tests were used to compare survival between groups. RESULTS: Life expectancies were significantly reduced for all diseases investigated compared with the local population (80.0 years) (p=0.05). GS had the longest life expectancy at 73.4 years, followed by NF1 at 71.5 years, NF2 at 69.0 years, FAP at 63.6 years, and VHL at 52.5 years. Patients diagnosed after establishment of the genetic register had an increase in survival compared to those diagnosed pre-1990: NF2 (14.7 years), FAP (13.9 years), VHL (16.3 years), and GS (11.2 years). CONCLUSION: Life expectancy for all five diseases was less than normal, although in recent years this reached the level of the local population in GS. Although there have been improvements in all conditions which may in part be attributable to better targeted care through the genetic register service, more needs to be done to address the very poor life expectancy in VHL.


Assuntos
Expectativa de Vida , Síndromes Neoplásicas Hereditárias/epidemiologia , Causas de Morte , Feminino , Humanos , Masculino , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/mortalidade , Sistema de Registros , Análise de Sobrevida , Taxa de Sobrevida
19.
Water Res ; 46(4): 1309-17, 2012 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-22209197

RESUMO

Contaminant removal from drinking water sources under reducing conditions conducive for the growth of denitrifying, arsenate reducing, and sulfate reducing microbes using a fixed-bed bioreactor may require oxygen-free gas (e.g., N2 gas) during backwashing. However, the use of air-assisted backwashing has practical advantages, including simpler operation, improved safety, and lower cost. A study was conducted to evaluate whether replacing N2 gas with air during backwashing would impact performance in a nitrate and arsenic removing anaerobic bioreactor system that consisted of two biologically active carbon reactors in series. Gas-assisted backwashing, comprised of 2 min of gas injection to fluidize the bed and dislodge biomass and solid phase products, was performed in the first reactor (reactor A) every two days. The second reactor (reactor B) was subjected to N2 gas-assisted backwashing every 3-4 months. Complete removal of 50 mg/L NO3- was achieved in reactor A before and after the switch from N2-assisted backwashing (NAB) to air-assisted backwashing (AAB). Substantial sulfate removal was achieved with both backwashing strategies. Prolonged practice of AAB (more than two months), however, diminished sulfate reduction in reactor B somewhat. Arsenic removal in reactor A was impacted slightly by long-term use of AAB, but arsenic removals achieved by the entire system during NAB and AAB periods were not significantly different (p>0.05) and arsenic concentrations were reduced from approximately 200 µg/L to below 20 µg/L. These results indicate that AAB can be implemented in anaerobic nitrate and arsenic removal systems.


Assuntos
Ar , Arsênio/isolamento & purificação , Reatores Biológicos/microbiologia , Água Potável/química , Nitratos/isolamento & purificação , Purificação da Água/instrumentação , Purificação da Água/métodos , Acetatos/isolamento & purificação , Anaerobiose , Cloretos/isolamento & purificação , Sulfatos/isolamento & purificação , Fatores de Tempo , Eliminação de Resíduos Líquidos
20.
Water Res ; 44(17): 4958-69, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20732708

RESUMO

A novel bioreactor system, consisting of two biologically active carbon (BAC) reactors in series, was developed for the simultaneous removal of nitrate and arsenic from a synthetic groundwater supplemented with acetic acid. A mixed biofilm microbial community that developed on the BAC was capable of utilizing dissolved oxygen, nitrate, arsenate, and sulfate as the electron acceptors. Nitrate was removed from a concentration of approximately 50 mg/L in the influent to below the detection limit of 0.2 mg/L. Biologically generated sulfides resulted in the precipitation of the iron sulfides mackinawite and greigite, which concomitantly removed arsenic from an influent concentration of approximately 200 ug/L to below 20 ug/L through arsenic sulfide precipitation and surface precipitation on iron sulfides. This study showed for the first time that arsenic and nitrate can be simultaneously removed from drinking water sources utilizing a bioreactor system.


Assuntos
Arsênio/isolamento & purificação , Reatores Biológicos , Nitratos/isolamento & purificação , Purificação da Água/instrumentação , Purificação da Água/métodos , Abastecimento de Água/análise , Biodegradação Ambiental , Solo , Espectroscopia por Absorção de Raios X , Difração de Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...