Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Introduction.

This article is the first of eight articles in this special issue on Family-Centered Early Intervention (FCEI) for children who are deaf or hard of hearing (DHH), or FCEI-DHH. In 2013, a diverse panel of experts published an international consensus statement on evidence-based Principles guiding FCEI-DHH. Those original Principles have been revised through a coproduction process involving multidisciplinary collaborators and an international consensus panel, utilizing the best available evidence and current understanding of how to optimally support children who are DHH and their families. This revision (referred to as expanded Principles) was motivated by the need to incorporate (a) input from family leaders and DHH leaders, (b) broader international and cultural perspectives, (c) new empirical evidence, and (d) research in human development. This Introduction provides an overview of the rationale, purposes, and main content areas to be addressed throughout the special issue.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Call to Action.

This Call to Action is the eighth and final article in this special issue on Family-Centered Early Intervention (FCEI) for children who are deaf or hard of hearing (DHH) and their families, or FCEI-DHH. Collectively, these articles highlight evidence-informed actions to enhance family well-being and to optimize developmental outcomes among children who are DHH. This Call to Action outlines actionable steps to advance FCEI-DHH supports provided to children who are DHH and their families. It also urges specific actions to strengthen FCEI-DHH programs/services and systems across the globe, whether newly emerging or long-established. Internationally, supports for children who are DHH are often siloed, provided within various independent sectors such as health/medicine, education, early childhood, and social and disability services. With this Call to Action, we urge invested parties from across relevant sectors to join together to implement and improve FCEI-DHH programs/services and systems, build the capacity of early intervention (EI) Providers and other professionals, extend research regarding FCEI-DHH, and fund EI supports, systems, and research, all with the aim of advancing outcomes for families and their children who are DHH.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Methods.

This is the fourth article in a series of eight that comprise a special issue on family-centered early intervention (FCEI) for children who are deaf or hard of hearing (DHH) and their families, FCEI-DHH. This article describes the co-production team and the consensus review method used to direct the creation of the 10 Principles described in this special issue. Co-production is increasingly being used to produce evidence that is useful, usable, and used. A draft set of 10 Principles for FCEI-DHH and associated Tables of recommended behaviors were developed using the knowledge creation process. Principles were refined through two rounds of eDelphi review. Results for each round were analyzed using measures of overall group agreement and measures that indicated the extent to which the group members agreed with each other. After Round 2, with strong agreement and low to moderate variation in extent of agreement, consensus was obtained for the 10 Principles for FCEI-DHH presented in this special issue. This work can be used to enhance evolution of FCEI-DHH program/services and systems world-wide and adds to knowledge in improvement science.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Foundation Principles.

This article is the fifth in a series of eight articles that comprise a special issue on Family-Centered Early Intervention (FCEI) for children who are deaf or hard of hearing (DHH) and their families, or FCEI-DHH. The 10 FCEI-DHH Principles are organized conceptually into three sections (a) Foundation Principles, (b) Support Principles, and (c) Structure Principles. Collectively, they describe the essential Principles that guide FCEI for children who are DHH and their families. This article describes the Foundation Principles (Principles 1 and Principle 2). The Foundation Principles emphasize the essential elements of ensuring that families with children who are DHH can access early intervention (EI) and other appropriate supports, as well as highlight the need for provision of EI that is family-centered. Implementation of these FCEI-DHH Principles is intended to improve the lives and the outcomes of children who are DHH and their families around the globe.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Cultural & Global Implications.

This article is the third in a series of eight articles that comprise this special issue on family-centered early intervention for children who are deaf or hard of hearing and their families (FCEI-DHH). It highlights the origins of FCEI-DHH in Western contexts and well-resourced locations and emphasizes the role of culture(s) in shaping FCEI-DHH. This article also cautions against the direct application of the 10 FCEI-DHH Principles presented in this issue across the globe without consideration of cultural implications. Cultural perceptions of decision-making processes and persons who can be decision-makers in FCEI-DHH are explored. Deaf culture(s) and the benefits of exposure to DHH adults with diverse backgrounds are introduced. Structural inequities that impact families' access to FCEI-DHH programs/services and systems, within and among nations and regions, are noted. The need to consider the cultural influences on families is emphasized; this applies to all levels of FCEI, including the development of systems through implementation of supports.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Support Principles.

This article is the sixth in a series of eight articles that comprise a special issue on Family-Centered Early Intervention (FCEI) for children who are deaf or hard of hearing (DHH) and their families, or FCEI-DHH. The Support Principles article is the second of three articles that describe the 10 Principles of FCEI-DHH, preceded by the Foundation Principles, and followed by the Structure Principles, all in this special issue. The Support Principles are composed of four Principles (Principles 3, 4, 5, and 6) that highlight (a) the importance of a variety of supports for families raising children who are DHH; (b) the need to attend to and ensure the well-being of all children who are DHH; (c) the necessity of building the language and communication abilities of children who are DHH and their family members; and (d) the importance of considering the family's strengths, needs, and values in decision-making.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Guiding Values.

This article is the second of eight articles in this special issue on Family-Centered Early Intervention (FCEI) for children who are deaf or hard of hearing (DHH) and their families, or FCEI-DHH. Five foundational values that guide FCEI-DHH are described, providing an evidence-informed, conceptual context for the 10 FCEI-DHH Principles and other articles presented in this issue. These values are applicable for Early Intervention (EI) Providers and other professionals on FCEI teams, as well as for FCEI-DHH programs/services and systems. The five key values include (1) being family-centered, (2) responding to diversity, (3) involving invested parties, especially families and individuals who are DHH, (4) supporting holistic child development, and (5) ensuring fundamental human rights. These evidence-informed values are considered essential to the effective provision of FCEI-DHH supports.

Family-Centered Early Intervention Deaf/Hard of Hearing (FCEI-DHH): Structure Principles.

This article is the seventh in a series of eight articles that comprise a special issue on family-centered early intervention for children who are deaf or hard of hearing and their families, or FCEI-DHH. This article, Structure Principles, is the third of three articles (preceded by Foundation Principles and Support Principles) that describe the 10 FCEI-DHH Principles. The Structure Principles include 4 Principles (Principle 7, Principle 8, Principle 9, and Principle 10) that highlight (a) the importance of trained and effective Early Intervention (EI) Providers, (b) the need for FCEI-DHH teams to work collaboratively to support families, (c) the considerations for tracking children's progress through developmental assessment, and (d) the essential role of progress monitoring to continuously improve systems.

The impact of decentralising colposcopy services from tertiary-level to primary-level care in inner-city Johannesburg, South Africa: a before and after study.

OBJECTIVE: To assess whether decentralising colposcopy services to a primary care facility in inner-city Johannesburg, South Africa raises access to colposcopy. DESIGN: Before-after study comparing 2 years before and 2 years after decentralisation, using clinical records and laboratory data on cervical cytology and histology. PRIMARY OUTCOME: The proportion of all women attending Hillbrow Community Health Centre (HCHC) with an abnormal Papanikolaou (Pap) smear who had a colposcopy post-decentralisation. SETTING: Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) has provided colposcopy services for several decades. HCHC, located about 3 km away, began colposcopy services in 2014. PARTICIPANTS: Women, aged above 18 years, who had a colposcopy for diagnosis and treatment of precancerous cervical lesions following a Pap smear, from 2012 to 2016 at CMJAH or HCHC. RESULTS: Pre-decentralisation at CMJAH, 910 women had colposcopy (2012-2014). Post-decentralisation (2014-2016), 721 had colposcopy at CMJAH and 399 at HCHC, the decentralised facility. The number who had a Pap smear at HCHC and then a colposcopy rose threefold post-decentralisation (114 vs 350). Post-decentralisation, 43 women at HCHC were referred to CMJAH for colposcopy, compared with 114 pre-decentralisation. Post-decentralisation, 47.3% of women at CMJAH waited >6 months for colposcopy, while 35.5% did at HCHC (p<0.001). Across all three groups, 26.9%-30.3% of women had cervical intraepithelial neoplasia III lesions or carcinoma on colposcopy. The proportion of invalid specimens was similar at CMJAH and HCHC (1.8%-2.8%). Of 401 women who had an abnormal Pap smear at HCHC post-decentralisation, 267 had colposcopy (66.6%). CONCLUSION: Decentralisation can decrease the time to colposcopy and reduce the workload of tertiary hospitals. Overall, more women accessed services. Colposcopy coverage at HCHC is higher than other sites, but could be further improved. Decentralisation did not appear to undermine the quality of services and this model could be extended to similar settings in South Africa and elsewhere.

A rare case of concomitant bilateral nipple and vulval condyloma accuminatum.

In this case study, we have presented a rare case of concomitant human papillomavirus condylomata lesions of both breast nipples and giant vulval warts in an HIV-positive woman on antiretroviral therapy. The woman underwent successful surgical excision and reconstruction for both breast nipple condylomata and vulval warts. Histology of the excised breast nipple and vulval tissue confirmed low-risk human papillomavirus infection. Concomitant vulval and bilateral breast nipple condylomata pose a management dilemma. It is possible that the pathogenesis of these lesions is through both direct contact spread as well as haematogenous dissemination of the human papillomavirus.

Familial aggregation of albuminuria and arterial hypertension in an Aboriginal Australian community and the contribution of variants in ACE and TP53.

BACKGROUND: Aboriginal Australians are at high risk of cardiovascular, metabolic and renal diseases, resulting in a marked reduction in life expectancy when compared to the rest of the Australian population. This is partly due to recognized environmental and lifestyle risk factors, but a contribution of genetic susceptibility is also likely. METHODS: Using results from a comprehensive survey of one community (N = 1350 examined individuals), we have tested for familial aggregation of plasma glucose, arterial blood pressure, albuminuria (measured as urinary albumin to creatinine ratio, UACR) and estimated glomerular filtration rate (eGFR), and quantified the contribution of variation at four candidate genes (ACE; TP53; ENOS3; MTHFR). RESULTS: In the subsample of 357 individuals with complete genotype and phenotype data we showed that both UACR (h2 = 64%) and blood pressure (sBP h2 = 29%, dBP, h2 = 11%) were significantly heritable. The ACE insertion-deletion (P = 0.0009) and TP53 codon72 polymorphisms (P = 0.003) together contributed approximately 15% of the total heritability of UACR, with an effect of ACE genotype on BP also clearly evident. CONCLUSIONS: While the effects of the ACE insertion-deletion on risk of renal disease (especially in the setting of diabetes) are well recognized, this is only the second study to implicate p53 genotype as a risk factor for albuminuria - the other being an earlier study we performed in a different Aboriginal community (McDonald et al., J Am Soc Nephrol 13: 677-83, 2002). We conclude that there are significant genetic contributions to the high prevalence of chronic diseases observed in this population.

Chromosomal radiosensitivity of human immunodeficiency virus positive/negative cervical cancer patients in South Africa.

Cervical cancer is the second most common cancer amongst South African women and is the leading cause of cancer-associated mortality in this region. Several international studies on radiation­induced DNA damage in lymphocytes of cervical cancer patients have remained inconclusive. Despite the high incidence of cervical cancer in South Africa, and the extensive use of radiotherapy to treat it, the chromosomal radiosensitivity of South African cervical cancer patients has not been studied to date. Since a high number of these patients are human immunodeficiency virus (HIV)­positive, the effect of HIV infection on chromosomal radiosensitivity was also investigated. Blood samples from 35 cervical cancer patients (20 HIV­negative and 15 HIV­positive) and 20 healthy controls were exposed to X­rays at doses of 6 MV of 2 and 4 Gy in vitro. Chromosomal radiosensitivity was assessed using the micronucleus (MN) assay. MN scores were obtained using the Metafer 4 platform, an automated microscopic system. Three scoring methods of the MNScore module of Metafer were applied and compared. Cervical cancer patients had higher MN values than healthy controls, with HIV­positive patients having the highest MN values. Differences between groups were significant when using a scoring method that corrects for false positive and false negative MN. The present study suggested increased chromosomal radiosensitivity in HIV-positive South African cervical cancer patients.

Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub-Saharan Africa.

In sub-Saharan Africa, invasive cervical cancer (ICC) incidence and mortality are among the highest in the world. This cross-sectional epidemiological study assessed human papillomavirus (HPV) prevalence and type distribution in women with ICC in Ghana, Nigeria, and South Africa. Cervical biopsy specimens were obtained from women aged ≥ 21 years with lesions clinically suggestive of ICC. Histopathological diagnosis of ICC was determined by light microscopy examination of hematoxylin and eosin stained sections of paraffin-embedded cervical specimens; samples with a confirmed histopathological diagnosis underwent HPV DNA testing by polymerase chain reaction. HPV-positive specimens were typed by reverse hybridization line probe assay. Between October 2007 and March 2010, cervical specimens from 659 women were collected (167 in Ghana, 192 in Nigeria and 300 in South Africa); 570 cases were histologically confirmed as ICC. The tumor type was identified in 551/570 women with ICC; squamous cell carcinoma was observed in 476/570 (83.5%) cases. The HPV-positivity rate in ICC cases was 90.4% (515/570). In ICC cases with single HPV infection (447/515 [86.8%]), the most commonly detected HPV types were HPV16 (51.2%), HPV18 (17.2%), HPV35 (8.7%), HPV45 (7.4%), HPV33 (4.0%) and HPV52 (2.2%). The prevalence of single and multiple HPV infections seemed higher among HIV-positive women and HPV type distribution appeared to differ according to tumor type and HIV status. In conclusion, HPV16, 18, 45 and 35 were the most common HPV types in sub-Saharan African women with ICC and HPV infections were more common in HIV-positive women.

Association between intrarenal arterial resistance and diastolic dysfunction in type 2 diabetes.

BACKGROUND: In comparison to the well established changes in compliance that occur at the large vessel level in diabetes, much less is known about the changes in compliance of the cardiovascular system at the end-organ level. The aim of this study was therefore to examine whether there was a correlation between resistance of the intrarenal arteries of the kidney and compliance of the left ventricle, as estimated by measurements of diastolic function, in subjects with type 2 diabetes. METHODS: We studied 167 unselected clinic patients with type 2 diabetes with a kidney duplex scan to estimate intrarenal vascular resistance, i.e. the resistance index (RI = peak systolic velocity-minimum diastolic velocity/peak systolic velocity) and a transthoracic echocardiogram (TTE) employing tissue doppler studies to document diastolic and systolic ventricular function. RESULTS: Renal RI was significantly higher in subjects with diastolic dysfunction (0.72 +/- 0.05) when compared with those who had a normal TTE examination (0.66 +/- 0.06, p < 0.01). Renal RI values were correlated with markers of diastolic dysfunction including the E/Vp ratio (r = 0.41, p < 0.001), left atrial area (r = 0.36, p < 0.001), the E/A ratio (r = 0.36, p < 0.001) and the E/E' ratio (r = 0.31, p < 0.001). These associations were independent of systolic function, hypertension, the presence and severity of chronic kidney disease, the use of renin-angiotensin inhibitors and other potentially confounding variables. CONCLUSION: Increasing vascular resistance of the intrarenal arteries was associated with markers of diastolic dysfunction in subjects with type 2 diabetes. These findings are consistent with the hypothesis that vascular and cardiac stiffening in diabetes are manifestations of common pathophysiological mechanisms.

Trifluoromethoxyl substituted phenylethylene diamines as high affinity sigma receptor ligands with potent anti-cocaine actions.

The phenylethylene diamines are a class of sigma receptor ligands with excellent selectivity over other biological systems and with anti-cocaine actions that involve antagonism of sigma1 receptors. In order to increase the potency of the aromatic methoxyl substituted analogues, trifluoromethoxyl groups were introduced to prevent metabolic demethylation. The para-substituted trifluoromethoxyl substituted analogues were shown to have increased sigma receptor affinity and represent the most potent anti-cocaine phenylethylene diamines yet described.

Functionalization of the 6,14-bridge of the orvinols. Part 3: preparation and pharmacological evaluation of 18- and 19-hydroxyl substituted orvinols.

The orvinols are a class of potent opioids which have been extensively studied, yet little is known about the effects of introducing substituents into the 18- and 19-positions. The etheno bridge of thevinone was hydroxylated to give both the 18- and 19-hydroxyl substituted thevinols. After 3-O-demethylation to the corresponding orvinols, binding and GTPgammaS functional assays indicated that hydroxyl substitution at the 18- and 19-positions differentially affects the mu opioid efficacy of orvinols.

3-Hydroxy-4-methoxyindolomorphinans as delta opioid selective ligands.

Previous studies showed that 4-hydroxy-3-methoxyindolomorphinans had variable delta opioid affinity and selectivity. Herein, we show that the 3,4-dimethoxy analogs possessed similar low affinity, whereas the 3-hydroxy-4-methoxy analogs showed excellent delta opioid affinity and selectivity comparable with the parent indolomorphinans.

Is nonalbuminuric renal insufficiency in type 2 diabetes related to an increase in intrarenal vascular disease?

OBJECTIVE: To investigate the role of intrarenal vascular disease in the pathogenesis of nonalbuminuric renal insufficiency in type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 325 unselected clinic patients who had sufficient clinical and biochemical information to calculate an estimated glomerular filtration rate (eGFR) using the Modified Diet in Renal Disease six-variable formula, at least two estimations of urinary albumin excretion rates (AER), and a renal duplex scan to estimate the resistance index of the interlobar renal arteries. The resistance index, measured as part of a complications surveillance program, was compared in patients with an eGFR < or >or=60 ml/min per 1.73 m(2) who were further stratified into normo- (AER <20), micro- (20-200), or macroalbuminuria (> 200 microg/min) categories. RESULTS: Patients with an eGFR <60 ml/min per 1.73 m(2) had a higher resistance index of the renal interlobar arteries compared with patients with an eGFR >or=60 ml/min per 1.73 m(2). However, the resistance index was elevated to a similar extent in patients with an eGFR <60 ml/min per 1.73 m(2) regardless of albuminuric status (normo- 0.74 +/- 0.01, micro- 0.73 +/- 0.01, and macroalbuminuria resistance index 0.75 +/- 0.11). Multiple regression analysis revealed that increased age (P < 0.0001), elevated BMI (P = 0.0001), decreased eGFR (P < 0.01), and decreased diastolic blood pressure (P < 0.01), but not an increased AER, were independently associated with an elevated resistance index in patients with impaired renal function. CONCLUSIONS: Subjects with type 2 diabetes and reduced glomerular filtration rate had similar degrees of intrarenal vascular disease, as measured by the intrarenal arterial resistance index, regardless of their AER status. The pathological mechanisms that determine the relationship between impaired renal function and AER status in subjects with type 2 diabetes remain to be elucidated.

Nonalbuminuric renal insufficiency in type 2 diabetes.

OBJECTIVE: To determine the prevalence and characteristics of patients with type 2 diabetes who have impaired renal function, defined as a glomerular filtration rate (GFR) <60 ml. min(-1). 1.73 m(-2), and normoalbuminuria. RESEARCH DESIGN AND METHODS: A cross-sectional survey of 301 outpatients attending a single tertiary referral center using the plasma disappearance of isotopic (99m)Tc-diethylene-triamine-penta-acetic acid to measure GFR and at least two measurements of urinary albumin excretion rate (AER) over 24 h to determine albuminuria. RESULTS: A total of 109 patients (36%) had a GFR <60 ml. min(-1). 1.73 m(-2). The overall prevalence of normo-, micro-, and macroalbuminuria was 43 of 109 (39%), 38 of 109 (35%), and 28 of 109 (26%), respectively. Compared with patients with macroalbuminuria, those with normoalbuminuria were more likely to be older and female. After excluding patients whose normoalbuminuric status was possibly related to the initiation of a renin-angiotensin system (RAS) inhibitor before the start of the study, the prevalence of a GFR <60 ml. min(-1). 1.73 m(-2) and normoalbuminuria was 23%. Temporal changes in GFR in a subset of 34 of 109 (32%) unselected patients with impaired renal function were available for comparison over a 3- to 10-year period. The rates of decline in GFR (ml. min(-1). 1.73 m(-2). year(-1)) of -4.6 +/- 1.0, -2.8 +/- 1.0, and -3.0 +/- 07 were not significantly different for normo- (n = 12), micro- (n = 12), and macroalbuminuric (n = 10) patients, respectively. CONCLUSIONS: These results suggest that patients with type 2 diabetes can commonly progress to a significant degree of renal impairment while remaining normoalbuminuric.