The development and maintenance of joint shape is critical for cartilage and bone biomechanics, integrity, and homeostasis. During long bone development, variations in rates of chondrocyte proliferation, hypertrophy, and matrix production within the articulo-epiphyseal cartilage complex produce the wide range of joint shapes and relative proportions of anatomical features. Difference in shape due to growth, repair, or disease, may affect or reflect joint-scale biomechanics, such as range of motion, as well as tissue-scale mechanics, such as cartilage stiffness. This dissertation aims to elucidate the relationship between joint shape and function, as well as advance the understanding of how joint shapes evolve during growth and deform in the presence of altered biomechanics during repair and in disease. The shape of the femur was assessed using 3-D local point registration and global statistical shape modeling techniques in animal models of growth and repair, and in human pediatric hip disorders. During cartilage repair, large shape deviations at the bone-cartilage interface were associated with local articular surface recession and low cartilage stiffness, establishing the importance of joint shape in the maintenance of cartilage biomechanics. During normal development of proximal and distal femoral shape, deformations and strains at the bone-cartilage interface were found to be site-specific and coordinated with changes at local growth plates. In humans, proximal femora underwent differential, growth-associated deformations and anisotropic areal dilations at the femoral head, femoral neck, and greater trochanter, with highest growth rates during puberty. Lastly, in the study of Legg-Calvé-Perthes disease and slipped capital femoral epiphysis, two pediatric hip disorders, proximal femora exhibited substantial disease- and site-specific deformations relative to the asymptomatic femur, with associated changes in growth plate normal vectors, suggesting biological and biomechanical mechanisms of shape deformation. This work demonstrated correlative links between structural features of the osteochondral unit in the femur and the biomechanical properties of the articular cartilage. Delineation of regional biomechanics and morphological changes contribute to the understanding of the mechanobiology of the proximal and distal femur. In addition, metrics of displacement and strain provide tangible targets for the development of future shape modulation therapies

Congenital syphilis is the result of placental transmission from mother to fetus of Treponema pallidum. Although congenital syphilis is preventable through timely treatment, the rate of new infections in the United States (US) has increased each year since 2013, and is increasing at a noticeably greater pace in California (CA). Most research into congenital syphilis has focused on individual psychosocial and behavioral factors that contribute to maternal vulnerability for syphilis. The aim of this study was to evaluate structural barriers to prenatal care access and utilization and congenital syphilis prevention in Kern County, CA. Transcripts from 8 in-depth interviews with prenatal care providers and 5 focus group discussions with 42 pregnant and postpartum persons were examined using thematic analysis. Structural barriers experienced by pregnant and postpartum persons to prenatal care access and utilization included (1) burdens of poverty; (2) stigma around substance use in pregnancy; (3) citizenship status; (4) lack of healthcare coverage; (5) low sexual health literacy; and (6) gender inequality Structural barriers experienced by prenatal care providers in congenital syphilis prevention included (1) limited guidance on clinical management of syphilis in pregnancy; (2) decay in public health infrastructure; and (3) inadequate support for managing patients' social comorbidities. The response to congenital syphilis prevention will require an examination of the complex context of social determinants of health in which persons diagnosed with syphilis live in.

Any metrology tool is only as good as it is calibrated. The characterization of metrology systems requires test patterns at a scale about ten times smaller than the measured features. The fabrication of patterns with linewidths down to 1.5 nm is described. The test sample was designed in such a way that the distribution of linewidths appears to be random at any location. This pseudorandom test pattern is used to characterize dimensional metrology equipment over its entire dynamic range by extracting the modulation transfer function of the system. The test pattern contains alternating lines of silicon and tungsten silicide, each according to its designed width. The fabricated test samples were imaged using a transmission electron microscope, a scanning electron microscope, and an atomic force microscope.

Objectives

To evaluate the efficacy of an in-language intervention of 2 lectures plus printed materials versus printed materials alone on knowledge and adherence to nutrition and physical activity guidelines among older Chinese Americans in San Francisco, California.

Methods

From August 2010 to September 2013, we randomized 756 Chinese Americans aged 50 to 75 years to either lectures plus print (n = 361) or print (n = 357). Clusters were the participants recruited by each lay health worker. Intervention outcomes were changes in knowledge of recommended vegetable intake, fruit intake, and physical activity level and adherence to those recommendations from pre- to 6 months postintervention.

Results

The retention rate was 99%. At baseline, knowledge and adherence to recommendations were low. Print yielded increases in knowledge of recommended vegetable intake and physical activity level and adherence to fruit intake and physical activity recommendations. Lectures plus print had significant increases in all 6 outcomes. In multivariable models, lectures plus print was superior to print for knowledge of vegetable (adjusted odds ratio [AOR] = 12.61; 95% confidence interval [CI] = 6.50, 24.45) and fruit (AOR = 16.16; 95% CI = 5.61, 46.51) intake recommendations and adherence to vegetable intake recommendations (AOR = 5.53; 95% CI = 1.96, 15.58).

Conclusions

In-language print materials, alone and combined with lectures, increased nutrition and physical activity knowledge and behaviors among older Chinese Americans.

This work reports on the development of a binary pseudo-random test sample optimized to calibrate the MTF of optical microscopes. The sample consists of a number of 1-D and 2-D patterns, with different minimum sizes of spatial artifacts from 300 nm to 2 microns. We describe the mathematical background, fabrication process, data acquisition and analysis procedure to return spatial frequency based instrument calibration. We show that the developed samples satisfy the characteristics of a test standard: functionality, ease of specification and fabrication, reproducibility, and low sensitivity to manufacturing error.

Chinese Americans have low colorectal cancer (CRC) screening rates. It is unclear whether physicians should offer all CRC screening modalities (fecal occult blood test [FOBT], sigmoidoscopy, colonoscopy) to Chinese Americans to increase screening. Seven hundred and twenty-five Chinese Americans were asked in a survey if their physician had ever recommended CRC screening and to self-report receipt and type of CRC screening. Participants whose physician had recommended all CRC screening modalities were significantly more likely to report ever having screening (adjusted odds ratio 4.29, 95% CI 1.26-14.68) and being up-to-date (4.06, 95% CI 2.13-7.74) than those who reported that their physician only recommended FOBT. Participants who received a recommendation of only one type of screening did not report a significant difference in ever having or being up-to-date for screening. A potential strategy to increase CRC screening among Chinese Americans is for clinicians to recommend all available CRC screening modalities to each patient.

Introduction

Chinese Americans have low colorectal cancer (CRC) screening rates. Evidence-based interventions to increase CRC screening in this population are lacking. This study aims to compare the efficacy of two interventions in increasing CRC screening among Chinese Americans.

Design

Cluster randomized comparative trial.

Setting/participants

From 2010 to 2014, a community-academic team conducted this study in San Francisco, CA with Chinese Americans aged 50-75 years who spoke English, Cantonese, or Mandarin.

Intervention

Lay health worker (LHW) intervention plus in-language brochure (LHW+Print) versus brochure (Print). LHWs in the LHW+Print arm were trained to teach participants about CRC in two small group sessions and two telephone calls.

Main outcome measures

Change in self-reports of ever having had CRC screening and being up to date for CRC screening from baseline to 6 months post-intervention. Statistical analysis was performed from 2014 to 2015.

Results

This study recruited 58 LHWs, who in turn recruited 725 participants. The average age of the participants was 62.2 years, with 81.1% women and 99.4% foreign born. Knowledge increase was significant (p<0.002) for nine measures in the LHW+Print group and six in the Print group. Both groups had increases in having ever been screened for CRC (LHW+Print, 73.9%-88.3%, p<0.0001; Print, 72.3%-79.5%, p=0.0003) and being up to date for CRC screening (LHW+Print, 60.0%-78.1%, p<0.0001; Print, 58.1%-64.1%, p=0.0003). In multivariable analyses, the intervention OR for LHW+Print versus Print was 1.94 (95% CI=1.34, 2.79) for ever screening and 2.02 (95% CI=1.40, 2.90) for being up to date.

Conclusions

Both in-language print materials and LHW outreach plus print materials increased CRC screening among Chinese Americans. The combination of LHW+Print was more effective than Print alone. These findings can guide clinicians and policymakers in choosing appropriate interventions to increase CRC screening among Chinese American immigrants.

Trial registration

This study is registered at www.clinicaltrials.gov NCT00947206.

Older Chinese immigrants are a growing population in the United States who experience multiple healthcare communication barriers such as limited English proficiency and low health literacy. Each of these obstacles has been associated with poor health outcomes but less is known about their effects in combination. This study examined the association between healthcare communication barriers and self-rated health among older Chinese immigrants. Cross-sectional survey data were obtained from 705 Chinese American immigrants ages 50-75 living in San Francisco, California. Communication barriers examined included spoken English proficiency, medical interpreter needs, and health literacy in written health information. The study sample (81 % females, mean age = 62) included 67 % who spoke English poorly or not at all, 34 % who reported needing a medical interpreter, and 37 % who reported "often" or "always" needing assistance to read health information. Two-thirds reported poor self-rated health; many reported having access to racial-concordant (74 %) and language-concordant (86 %) healthcare services. Both poor spoken English proficiency and low health literacy were associated with poor self-rated health, independent of other significant correlates (unemployment, chronic health conditions, and having a primary doctor who was ethnic Chinese). Results revealed that spoken English proficiency and print health literacy are independent communication barriers that are directly associated with health status among elderly Chinese American immigrants. Access to racial- or language-concordant health care services did not appear to resolve these barriers. These findings underscore the importance of addressing both spoken and written healthcare communication needs among older Chinese American immigrants.

Phase 3 studies combining histone deacetylase inhibitors with bortezomib were hampered by gastrointestinal (GI) intolerance, which was not observed when combined with immunomodulatory drugs. This study is a single-center phase 2 study of panobinostat with lenalidomide and dexamethasone (FRD). Twenty-seven relapsed multiple myeloma patients were enrolled. Twenty-two patients (81%) were lenalidomide refractory and 9 (33%), 14 (52%), and 7 (26%) were refractory to pomalidomide, bortezomib, and carfilzomib, respectively. High-risk molecular findings were present in 17 (63%) patients. Responses included 2 complete responses (CRs), 4 very good partial responses (VGPRs), 5 partial responses (PRs), and 9 minimal responses (MRs) for an overall response rate of 41%, clinical benefit rate of 74%, and a disease control rate of 96%. The median progression-free survival (PFS) was 7.1 months. In the 22 lenalidomide-refractory patients, there were 1 CR, 4 VGPRs, 3 PRs, and 7 MRs, with a median PFS of 6.5 months. Median overall survival was not reached. Grade 3/4 toxicities were primarily hematologic. Gene expression profiling of enrollment tumor samples revealed a set of 1989 genes associated with short (<90 days) PFS to therapy. MAGEA1 RNA and protein expression were correlated with short PFS, and laboratory studies demonstrated a role for MAGE-A in resistance to panobinostat-induced cell death. FRD demonstrates durable responses, even in high-risk, lenalidomide-refractory patients, indicating the essential role of panobinostat in attaining responses. MAGEA1 expression may represent a functional biomarker for resistance to panobinostat. In contrast to PANORAMA 1, there were no significant GI toxicities and primarily expected hematologic toxicities. This trial was registered at www.clinicaltrials.gov as #NCT00742027.