On July 9, 2002, Governor Gray Davis signed the California Voting Rights Act (CVRA) into law. The intent of the CVRA was to build upon the voting rights protections embodied in the Federal Voting Rights Act (FVRA) by enhancing the influence of minority populations in local government elections. The CVRA has led to multiple legal challenges of at-large electoral systems in dozens of governments in California. This paper explores the impacts of the CVRA on local governments as well as potential impacts of recent changes to the CVRA.

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD). Neuropathology consistent with AD is present by 40 years of age and dementia may develop up to a decade later. In this review, we describe metabolic and vascular neuroimaging studies in DS that suggest these functional changes are a key feature of aging, linked to cognitive decline and AD in this vulnerable cohort. FDG-PET imaging in DS suggests systematic reductions in glucose metabolism in posterior cingulate and parietotemporal cortex. Magentic resonance spectroscopy studies show consistent decreases in neuronal health and increased myoinositol, suggesting inflammation. There are few vascular imaging studies in DS suggesting a gap in our knowledge. Future studies would benefit from longitudinal measures and combining various imaging approaches to identify early signs of dementia in DS that may be amenable to intervention.

This review focuses on the role of Aβ in AD pathogenesis in Down syndrome and current approaches for imaging Aβ in vivo. We will describe how Aβ deposits with age, the posttranslational modifications that can occur, and detection in biofluids. Three unique case studies describing partial trisomy 21 cases without APP triplication, and the occurrences of low level mosaic trisomy 21 in an early onset AD patient are presented. Brain imaging for Aβ includes those by positron emission tomography and ligands (Pittsburgh Compound B, Florbetapir, and FDDNP) that bind Aβ have been published and are summarized here. In combination, we have learned a great deal about Aβ in DS in terms of characterizing age of onset of this pathology and it is exciting to note that there is a clinical trial in DS targeting Aβ that may lead to clinical benefits.

The brain-blood partition coefficient (BBPC) is necessary for quantifying cerebral blood flow (CBF) when using tracer based techniques like arterial spin labeling (ASL). A recent improvement to traditional MRI measurements of BBPC, called calibrated short TR recovery (CaSTRR), has demonstrated a significant reduction in acquisition time for BBPC maps in mice. In this study CaSTRR is applied to a cohort of healthy canines (n = 17, age = 5.0 - 8.0 years) using a protocol suited for application in humans at 3T. The imaging protocol included CaSTRR for BBPC maps, pseudo-continuous ASL for CBF maps, and high resolution anatomical images. The standard CaSTRR method of normalizing BBPC to gadolinium-doped deuterium oxide phantoms was also compared to normalization using hematocrit (Hct) as a proxy value for blood water content. The results show that CaSTRR is able to produce high quality BBPC maps with a 4 min acquisition time. The BBPC maps demonstrate significantly higher BBPC in gray matter (0.83 ± 0.05 mL/g) than in white matter (0.78 ± 0.04 mL/g, p = 0.006). Maps of CBF acquired with pCASL demonstrate a negative correlation between gray matter perfusion and age (p = 0.003). Voxel-wise correction for BBPC is also shown to improve contrast to noise ratio between gray and white matter in CBF maps. A novel aspect of the study was to show that that BBPC measurements can be calculated based on the known Hct of the blood sample placed in scanner. We found a strong correlation (R ² = 0.81 in gray matter, R ² = 0.59 in white matter) established between BBPC maps normalized to the doped phantoms and BBPC maps normalized using Hct. This obviates the need for doped water phantoms which simplifies both the acquisition protocol and the post-processing methods. Together this suggests that CaSTRR represents a feasible, rapid method to account for BBPC variability when quantifying CBF. As canines have been used widely for aging and Alzheimer's disease studies, the CaSTRR method established in the animals may further improve CBF measurements and advance our understanding of cerebrovascular changes in aging and neurodegeneration.

BACKGROUND: Physician Orders for Life Sustaining Treatment (POLST) document instructions for intensity of care based upon patient care preferences. POLST forms generally reflect patients wishes and dictate subsequent medical care, but it is not known how POLST use and content among nursing home residents is associated with inpatient utilization across a large population. OBJECTIVE: Evaluate the relationship between POLST use and content with hospital utilization among nursing home residents in California. DESIGN: Retrospective cohort study using the Minimum Data Set linked to California Section S (POLST documentation), the Medicare Beneficiary Summary File, and Medicare line item claims. PATIENTS: California nursing home residents with Medicare fee-for-service insurance, 2011-2016. MAIN MEASURES: Hospitalization, days in the hospital, and days in the intensive care unit (ICU) after adjustment for resident and nursing home characteristics. KEY RESULTS: The 1,112,834 residents had a completed and signed (valid) POLST containing orders for CPR with Full treatment 29.6% of resident-time (in person-years) and a DNR order with Selective treatment or Comfort care 27.1% of resident-time. Unsigned POLSTs accounted for 11.3% of resident-time. Residents experienced 14 hospitalizations and a mean of 120 hospital days and 37 ICU days per 100 person-years. Residents with a POLST indicating CPR Full treatment had utilization nearly identical to residents without a POLST. A gradient of decreased utilization was related to lower intensity of care orders. Compared to residents without a POLST, residents with a POLST indicating DNR Comfort care spent 56 fewer days in the hospital and 22 fewer days in the ICU per 100 person-years. Unsigned POLST had a weaker and less consistent relationship with hospital utilization. CONCLUSIONS: Among California NH residents, there is a direct relationship between intensity of care preferences in POLST and hospital utilization. These findings emphasize the importance of a valid POLST capturing informed preferences for nursing home residents.

BACKGROUND: Physician Orders for Life-Sustaining Treatment (POLST) facilitates documentation and transition of patients life-sustaining treatment orders across care settings. Little is known about patient and facility factors related to care preferences within POLST across a large, diverse nursing home population. We describe the orders within POLST among all nursing home (NH) residents in California from 2011 to 2016. METHODS: California requires NHs to document in the Minimum Data Set whether residents complete a POLST and orders within POLST. Using a serial cross-sectional design for each year, we describe POLST completion and orders for all California NH residents from 2011 to 2016 (N = 1,112,668). We used logistic mixed-effects regression models to estimate POLST completion and resuscitation orders to understand the relationship with resident and facility characteristics, including Centers for Medicare and Medicaid Services (CMS) Nursing Home Compare overall five-star quality rating. RESULTS: POLST completion significantly increased from 2011 to 2016 with most residents having a POLST in 2016 (short-stay:68%; long-stay:81%). Among those with a POLST in 2016, 54% of long-stay and 41% of short-stay residents had a DNR order. Among residents with DNR, >90% had orders for limited medical interventions or comfort measures. Few residents (<6%) had a POLST with contradictory orders. In regression analyses, POLST completion was greater among residents with more functional dependence, but was lower among those with more cognitive impairment. Greater functional and cognitive impairment were associated with DNR orders. Racial and ethnic minorities indicated more aggressive care preferences. Higher CMS five-star facility quality rating was associated with greater POLST completion. CONCLUSIONS: Six years after a state mandate to document POLST completion in NHs, most California NH residents have a POLST, and about half of long-stay residents have orders to limit life-sustaining treatment. Future work should focus on determining the quality of care preference decisions documented in POLST.

BACKGROUND: Physician Orders for Life-Sustaining Treatment (POLST) are commonly used for nursing home (NH) residents. Treatment orders differ across race and ethnicity, presumably related to cultural and socioeconomic variation and levels of access to care and trust. Because national efforts focus on addressing the underpinnings of racial and ethnic differences in treatment (i.e., access to care and trust), we describe POLST use and content by race and ethnicity. METHODS: California requires NHs to document POLST completion and content in the Minimum Data Set. We describe POLST completion and content for all California NH residents from 2011 to 2016 (N = 1,120,376). Adjusting for resident characteristics, we compared changes in completion rate and differences by race and ethnicity in POLST content-orders for cardiopulmonary resuscitation (CPR), do not resuscitate (DNR), CPR with full treatment, DNR with selective treatment or comfort orders, and if unsigned. RESULTS: POLST completion increased across all racial and ethnic groups from 2011 to 2016; by 2016, NH residents had a POLST two-thirds or more of the time. In 2011, Black residents had a POLST with a CPR order 30.4% of the time, Hispanic residents 25.6%, and White residents 19.7%. By 2016, this grew to 42.5%, 38.2%, and 28.1%, respectively, with Black and Hispanic residents demonstrating larger increases than White residents (p < 0.001). Increases over time in POLST with CPR and full treatment were greater for Black and Hispanic residents compared to White residents. The increase in POLST with DNR and DNR with Selective treatment and Comfort orders was greater for White compared to Black patients (p < 0.001). Unsigned POLST with CPR and DNR orders decreased across all racial and ethnic groups. CONCLUSIONS: Racial and ethnic differences in POLST intensity of care orders increased between 2011 and 2016 suggesting that efforts to mitigate factors underlying differences were ineffective. Studies of newer POLST data are imperative.

Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly in the frontal lobes. Across all DS adults, poorer Brief Praxis Test performance correlated with reduced FA in the corpus callosum as well as several association tracts, primarily within frontoparietal regions. Our results demonstrate significantly lower WM integrity in DS compared with controls, particularly in the frontal tracts. DS-related WM integrity reductions in a number of tracts were associated with poorer cognition. These preliminary results suggest that late myelinating frontal pathways may be vulnerable to aging in DS.

Introduction

Displacement encoding with stimulated echoes (DENSE) is a phase contrast technique that encodes tissue displacement into phase images, which are typically processed into measures of cardiac function such as strains. For improved signal to noise ratio and spatiotemporal resolution, DENSE is often acquired with a spiral readout using an 11.1 ms readout duration. However, long spiral readout durations are prone to blurring due to common phenomena such as off-resonance and T2* decay, which may alter the resulting quantifications of strain. We hypothesized that longer readout durations would reduce image quality and underestimate cardiac strains at both 3.0 T and 1.5 T and that using short readout durations could overcome these limitations.

Material and methods

Computational simulations were performed to investigate the relationship between off-resonance and T2* decay, the spiral cine DENSE readout duration, and measured radial and circumferential strain. Five healthy participants subsequently underwent 2D spiral cine DENSE at both 3.0 T and 1.5 T with several different readout durations 11.1 ms and shorter. Pearson correlations were used to assess the relationship between cardiac strains and the spiral readout duration.

Results

Simulations demonstrated that long readout durations combined with off-resonance and T2* decay yield blurred images and underestimate strains. With the typical 11.1 ms DENSE readout, blurring was present in the anterior and lateral left ventricular segments of participants and was markedly improved with shorter readout durations. Radial and circumferential strains from those segments were significantly correlated with the readout duration. Compared to the 1.9 ms readout, the 11.1 ms readout underestimated radial and circumferential strains in those segments at both field strengths by up to 19.6% and 1.5% (absolute), or 42% and 7% (relative), respectively.

Conclusions

Blurring is present in spiral cine DENSE images acquired at both 3.0 T and 1.5 T using the typical 11.1 ms readout duration, which yielded substantially reduced radial strains and mildly reduced circumferential strains. Clinical studies using spiral cine DENSE should consider these limitations, while future technical advances may need to leverage accelerated techniques to improve the robustness and accuracy of the DENSE acquisition rather than focusing solely on reduced acquisition time.

Kidneys contribute to glucose homeostasis by reabsorbing filtered glucose in the proximal tubules via sodium-glucose cotransporters (SGLTs). Reabsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, canagliflozin, and empagliflozin, increase glucose excretion and lower blood glucose levels. To resolve unanswered questions about these inhibitors, we developed a novel approach to map the distribution of functional SGLT2 proteins in rodents using positron emission tomography with 4-[¹⁸F]fluoro-dapagliflozin (F-Dapa). We detected prominent binding of intravenously injected F-Dapa in the kidney cortexes of rats and wild-type and Sglt1-knockout mice but not Sglt2-knockout mice, and injection of SGLT2 inhibitors prevented this binding. Furthermore, imaging revealed only low levels of F-Dapa in the urinary bladder, even after displacement of kidney binding with dapagliflozin. Microscopic ex vitro autoradiography of kidney showed F-Dapa binding to the apical surface of early proximal tubules. Notably, in vivo imaging did not show measureable specific binding of F-Dapa in heart, muscle, salivary glands, liver, or brain. We propose that F-Dapa is freely filtered by the kidney, binds to SGLT2 in the apical membranes of the early proximal tubule, and is subsequently reabsorbed into blood. The high density of functional SGLT2 transporters detected in the apical membrane of the proximal tubule but not detected in other organs likely accounts for the high kidney specificity of SGLT2 inhibitors. Overall, these data are consistent with data from clinical studies on SGLT2 inhibitors and provide a rationale for the mode of action of these drugs.