Assessment of Patient Satisfaction and Treatment Outcomes in Digital Smile Design vs. Conventional Smile Design: A Randomized Controlled Trial.

Background: The esthetics of a smile holds significant importance in an individual's self-esteem and overall quality of life. In the realm of cosmetic dentistry, smile design has traditionally relied on conventional methods, but recent advances in technology have introduced digital smile design (DSD) as a promising alternative. Materials and Methods: In this randomized controlled trial, 150 adult patients seeking smile enhancement procedures were enrolled and randomly assigned to one of two groups: the DSD group or the conventional smile design group. The DSD group underwent smile design using digital technology, including intraoral scans, computer-aided design, and 3D simulations. Meanwhile, the conventional smile design group received smile design through traditional methods, involving manual impressions, stone models, and manual wax-ups. Patient satisfaction was measured using a visual analog scale (VAS) ranging from 0 to 100 immediately after the procedure, while treatment outcomes were assessed three months post-procedure by dental professionals using a standardized assessment scale. Results: In terms of patient satisfaction, the DSD group demonstrated a mean score of 85.4 (SD ± 6.2), while the conventional smile design group had a mean score of 79.8 (SD ± 7.1). This suggests that patients in the DSD group reported higher levels of satisfaction with their smile enhancements. Regarding treatment outcomes, 92% of patients in the DSD group exhibited excellent restoration fit, occlusion, and esthetics, whereas 78% of patients in the conventional smile design group achieved the same level of excellence. These findings collectively indicate that digital smile design (DSD) may yield superior patient satisfaction and improved treatment outcomes when compared to conventional smile design methods, particularly with regard to esthetic results and overall patient contentment. Conclusion: In conclusion, the results of this randomized controlled trial emphasize the potential advantages of integrating digital technology into smile design procedures.

Sustainability in Membrane Technology: Membrane Recycling and Fabrication Using Recycled Waste.

Membrane technology has shown a promising role in combating water scarcity, a globally faced challenge. However, the disposal of end-of-life membrane modules is problematic as the current practices include incineration and landfills as their final fate. In addition, the increase in population and lifestyle advancement have significantly enhanced waste generation, thus overwhelming landfills and exacerbating environmental repercussions and resource scarcity. These practices are neither economically nor environmentally sustainable. Recycling membranes and utilizing recycled material for their manufacturing is seen as a potential approach to address the aforementioned challenges. Depending on physiochemical conditions, the end-of-life membrane could be reutilized for similar, upgraded, and downgraded operations, thus extending the membrane lifespan while mitigating the environmental impact that occurred due to their disposal and new membrane preparation for similar purposes. Likewise, using recycled waste such as polystyrene, polyethylene terephthalate, polyvinyl chloride, tire rubber, keratin, and cellulose and their derivates for fabricating the membranes can significantly enhance environmental sustainability. This study advocates for and supports the integration of sustainability concepts into membrane technology by presenting the research carried out in this area and rigorously assessing the achieved progress. The membranes' recycling and their fabrication utilizing recycled waste materials are of special interest in this work. Furthermore, this study offers guidance for future research endeavors aimed at promoting environmental sustainability.

Ethnic inequalities during clinical placement: A qualitative study of student nurses' experiences within the London National Health Service.

AIM: To understand how student nurse experiences on clinical placement, within National Health Service (NHS) hospitals, differ for ethnic minority and White British groups. DESIGN: A qualitative thematic analysis with an inductive approach. METHODS: Data from semi-structured interviews with 21 London (United Kingdom) hospital-based student nurses were examined using thematic analysis. Participants were interviewed as part of the Tackling Inequalities and Discrimination Experiences in Health Services (TIDES) study and asked about their experiences during clinical placement. RESULTS: Five main themes were identified: (1) Role of mentors, (2) Discrimination and unfair treatment, (3) Speaking up/out, (4) Career progression, and (5) Consequences of adverse experiences. All themes were linked, with the social dynamics and workplace environment (referred to as "ward culture") providing a context that normalizes mistreatment experienced by nursing students. Students from ethnic minority backgrounds reported racism as well as cultural and/or religious microaggressions. While being valued for their race and ethnicity, White British students also experienced discrimination and inequity due to their age, sex, gender, and sexual orientation. Students from both White British and ethnic minority groups acknowledged that being treated badly was a barrier to career progression. Ethnic minority students also noted the lack of diverse representation within senior nursing positions discouraged career progression within the UK NHS. CONCLUSION: These initial experiences of inequality and discrimination are liable to shape a student's perspective of their profession and ability to progress within nursing. The NHS is responsible for ensuring that student nurses' developmental opportunities are equal, irrespective of ethnicity. IMPACT: Ward culture is perpetuated by others who normalize mistreatment and concurrently disadvantage ethnic minority students, making them feel unvalued. This in turn impacts both staff retention and career progression within the NHS. Training assessors should be aware of the existing culture of discrimination within clinical placements and work to eradicate it.

Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension.

Genome-wide association studies of blood pressure (BP) have identified >1,000 loci, but the effector genes and biological pathways at these loci are mostly unknown. Using published association summary statistics, we conducted annotation-informed fine-mapping incorporating tissue-specific chromatin segmentation and colocalization to identify causal variants and candidate effector genes for systolic BP, diastolic BP, and pulse pressure. We observed 532 distinct signals associated with ≥2 BP traits and 84 with all three. For >20% of signals, a single variant accounted for >75% posterior probability, 65 were missense variants in known (SLC39A8, ADRB2, and DBH) and previously unreported BP candidate genes (NRIP1 and MMP14). In disease-relevant tissues, we colocalized >80 and >400 distinct signals for each BP trait with cis-eQTLs and regulatory regions from promoter capture Hi-C, respectively. Integrating mouse, human disorder, gene expression and tissue abundance data, and literature review, we provide consolidated evidence for 436 BP candidate genes for future functional validation and discover several potential drug targets.

The experiences of people living with environmental sensitivities concerning oral health and access to dental services.

PURPOSE: Because people living with environmental sensitivities are poorly acknowledged in our society, we still know very little about their experiences navigating in the health care system, especially with respect to dental services. Our objective, therefore, was to describe their dental care pathway and better understand their experiences accessing oral health services. MATERIALS AND METHODS: A qualitative descriptive study was conducted in partnership with organizations supporting people with environmental sensitivities. Through a criterion sampling technique, 12 people living with environmental sensitivities in Quebec (Canada) were invited to participate in individual semi-structured interviews. These interviews lasted around 90 min and were transcribed to be thematically analysed. RESULTS: Participants faced major barriers accessing dental services and thus lived for long periods of time with unmet dental needs. Their dental care pathways were often delayed or even interrupted for several reasons. First because they were exposed to pollutants upon leaving their house, which rendered their trip to the dentist perilous. Second because dentists lacked knowledge about environmental sensitivities and seemed reluctant to accommodate them. CONCLUSIONS: We invite governments, dental professionals, and researchers to develop policies and clinical approaches for improving people living with environmental sensitivities' quality of life and access to dental services.IMPLICATIONS FOR REHABILITATIONAlthough environmental sensitivities are recognized as disability in several countries such as Sweden and Germany, people with these conditions face major barriers to access healthcare services.Dental professionals, for instance, are reluctant to acknowledge environmental sensitivities as a disability and seldom accommodate sufferers' special needs.We invite dentists to foster holistic and person-centered approaches and be receptive to the health conditions and needs of people with environmental sensitivities.Dentists could address oral health needs of people with environmental sensitivities by doing home-visits with portable dental equipment as this removes barriers related to their exposure to pollutants.

Entomopathogenic Fungi: An Eco-Friendly Synthesis of Sustainable Nanoparticles and Their Nanopesticide Properties.

The agricultural industry could undergo significant changes due to the revolutionary potential of nanotechnology. Nanotechnology has a broad range of possible applications and advantages, including insect pest management using treatments based on nanoparticle insecticides. Conventional techniques, such as integrated pest management, are inadequate, and using chemical pesticides has negative consequences. As a result, nanotechnology would provide ecologically beneficial and effective alternatives for insect pest control. Considering the remarkable traits they exhibit, silver nanoparticles (AgNPs) are recognized as potential prospects in agriculture. Due to their efficiency and great biocompatibility, the utilization of biologically synthesized nanosilver in insect pest control has significantly increased nowadays. Silver nanoparticles have been produced using a wide range of microbes and plants, which is considered an environmentally friendly method. However, among all, entomopathogenic fungi (EPF) have the most potential to be used in the biosynthesis of silver nanoparticles with a variety of properties. Therefore, in this review, different ways to get rid of agricultural pests have been discussed, with a focus on the importance and growing popularity of biosynthesized nanosilver, especially silver nanoparticles made from fungi that kill insects. Finally, the review highlights the need for further studies so that the efficiency of bio-nanosilver could be tested for field application and the exact mode of action of silver nanoparticles against pests can be elucidated, which will eventually be a boon to the agricultural industry for putting a check on pest populations.

Large-scale agricultural burning and cardiorespiratory emergency department visits in the U.S. state of Kansas.

BACKGROUND: Prescribed agricultural burning is a common land management practice, but little is known about the health effects from the resulting smoke exposure. OBJECTIVE: To examine the association between smoke from prescribed burning and cardiorespiratory outcomes in the U.S. state of Kansas. METHODS: We analyzed a zip code-level, daily time series of primary cardiorespiratory emergency department (ED) visits for February-May (months when prescribed burning is common in Kansas) in the years 2009-2011 (n = 109,220). Given limited monitoring data, we formulated a measure of smoke exposure using non-traditional datasets, including fire radiative power and locational attributes from remote sensing data sources. We then assigned a population-weighted potential smoke impact factor (PSIF) to each zip code, based on fire intensity, smoke transport, and fire proximity. We used Poisson generalized linear models to estimate the association between PSIF on the same day and in the past 3 days and asthma, respiratory including asthma, and cardiovascular ED visits. RESULTS: During the study period, prescribed burning took place on approximately 8 million acres in Kansas. Same-day PSIF was associated with a 7% increase in the rate of asthma ED visits when adjusting for month, year, zip code, meteorology, day of week, holidays, and correlation within zip codes (rate ratio [RR]: 1.07; 95% confidence interval [CI]: 1.01, 1.13). Same-day PSIF was not associated with a combined outcome of respiratory ED visits (RR [95% CI]: 0.99 [0.97, 1.02]), or cardiovascular ED visits (RR [95% CI]: 1.01 [0.98, 1.04]). There was no consistent association between PSIF during the past 3 days and any of the outcomes. SIGNIFICANCE: These results suggest an association between smoke exposure and asthma ED visits on the same day. Elucidating these associations will help guide public health programs that address population-level exposure to smoke from prescribed burning.

Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways.

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

Strengthening the Bridge Between Academic and the Industry Through the Academia-Industry Collaboration Plan Design Model.

The study has been undertaken to integrate two different aspects of the triple helix model: universities and the industry. Special attention has been paid to the prevailing difference between the two, hampering their working as a coherent unit. Integrating the existing knowledge in the study, we proposed the Academia-Industry Collaboration Plan (AICP) design model. The model comprises processes, methods or approaches, and tools. Processes serve as a road map to third parties for establishing collaboration between academia and the industry. It has all the essential process models and a series of steps that help minimize the organizational complexity of the collaboration process between academia and the industry. Methods or approaches serve the purpose of implementing those processes effectively. Finally, appropriate tools are selected to integrate possible collaboration improvements that lead to innovation.

Retrospective audit of CT scans performed at a hospital for surgical patients.

Introduction: Easy accessibility, high sensitivity and specificity of CT scans have markedly increased its usage in developed countries. Its importance is undeniably considered integral for the diagnosis of various pathologies. However, sometimes this costly resource is wasted when used unnecessary. This paper is an audit on CT scans performed to look for surgical pathologies between July 2018 and April 2019 recapitulating the numbers of CT scan's abnormal and normal findings. Methodology: Anonymized record of all the patients seen by the surgical team in the emergency department was reviewed. Retrospective data of every patient who had the CT scan was taken through Mckesson Radiology software of an Irish Hospital. Analysis was done using SPSS. Findings of 102 CT scans was broken down in to three different groups depending at which departmental level CT was performed, namely:Emergency department, Inpatient and Outpatient. Results: 102 CT Scans were performed of which 51 (50%) patients out of all the three groups had unremarkable. Conclusions: Adequate history, proper clinical examination and strong clinical knowledge may bring down the number of unnecessary CT scans.

Trichoderma: An Eco-Friendly Source of Nanomaterials for Sustainable Agroecosystems.

Traditional nanoparticle (NP) synthesis methods are expensive and generate hazardous products. It is essential to limit the risk of toxicity in the environment from the chemicals as high temperature and pressure is employed in chemical and physical procedures. One of the green strategies used for sustainable manufacturing is microbial nanoparticle synthesis, which connects microbiology with nanotechnology. Employing biocontrol agents Trichoderma and Hypocrea (Teleomorphs), an ecofriendly and rapid technique of nanoparticle biosynthesis has been reported in several studies which may potentially overcome the constraints of the chemical and physical methods of nanoparticle biosynthesis. The emphasis of this review is on the mycosynthesis of several metal nanoparticles from Trichoderma species for use in agri-food applications. The fungal-cell or cell-extract-derived NPs (mycogenic NPs) can be applied as nanofertilizers, nanofungicides, plant growth stimulators, nano-coatings, and so on. Further, Trichoderma-mediated NPs have also been utilized in environmental remediation approaches such as pollutant removal and the detection of pollutants, including heavy metals contaminants. The plausible benefits and pitfalls associated with the development of useful products and approaches to trichogenic NPs are also discussed.

A three-factor benefits framework for understanding consumer preference for scented household products: psychological interactions and implications for future development.

Humans have deliberately scented their environment for purpose or pleasure for millennia. In the contemporary marketplace most consumers prefer and purchase scented versions of common household products. However, the drivers of this consumer preference have not been elucidated. To explain the attraction to scent in household products we propose a novel three-factor framework, comprising functional benefits (malodor mitigation, base odor coverage, freshening), in-use experience benefits (cleanliness, efficacy, pleasure), and emotional benefits (increasing in confidence, mood and nostalgia). To support this framework, we present new data from a market research survey on US consumer purchasing habits and attitudes towards home cleaning, laundry, and air freshening products. Further substantiating our framework, a focused review of olfactory psychological science illustrating the central role of scent in cognition, wellbeing, motivated behavior, and social behavior, as well as sensory marketing research highlights the benefits and implications of scent in consumer household products. Based on our three-factor framework we go on to discuss the potential for scent to influence health and raise issues to consider (such as potential negative responding to fragranced products). We conclude by showcasing new opportunities for future research in olfactory science and on scented household products that can advance the positive impacts of scent.

Leiomyosarcoma of the spermatic cord: a rare paratesticular neoplasm case report.

BACKGROUND: Primary soft tissue sarcomas contribute to only 2% of all malignancies arising from the male genitourinary tract. Leiomyosarcoma (LMS) is a malignant soft tissue neoplasm which originates from the mesenchyme and has a characteristic smooth muscle differentiation. Usually, it presents as a painless, firm, slow-growing unilateral scrotal mass. Investigations include imaging, tumor markers, and histopathology. CASE PRESENTATION: A 65-year-old gentleman known diabetic and beta-thalassemic trait was referred to the Urology OPD at Letterkenny University Hospital. His presenting complaint was a left groin lump that appeared 1 year ago and was growing larger in size gradually. According to the patient, his lump was slightly painful (localized) initially that later became painless. He did not report any testicular trauma/infection or UTI. There was no significant history of malignancies running through his family. Clinical examination revealed a soft and lax abdomen, normal testes. There was a non-tender 2cm x 2cm well-circumscribed, mobile, firm to cystic irreducible left inguinoscrotal mass and appeared to be attached to the spermatic cord. Cough impulse was indiscernible. Ultrasound left groin showed 1.8 cm transverse x 1.4 cm AP x 1.9 cm sagittal) well-circumscribed ovoid nodular subcutaneous lesion present in the upper left inguinal area just lateral to the left pubic tubercle that appeared solid with heterogeneous internal echotexture and no internal calcification. Some internal vascularity is demonstrated with color Doppler assessment. CONCLUSION: Because of its rareness, LMS represents a management conundrum. There is no standard protocol for treatment. We present a case and discuss the available evidence from the literature to date to help identify LMS of the spermatic cord that is highly unusual.

Lessons Learned From a Qualitative COVID-19 Investigation Among Essential Workers With Limited English Proficiency in Southwest Kansas.

In this commentary, we briefly describe our methodology in conducting a remote qualitative investigation with essential workers from southwest Kansas, and then describe some key considerations, challenges, and lessons learned in recruiting and conducting interviews remotely. From August 4, 2020 through August 26, 2020, Centers for Disease Control and Prevention (CDC) staff conducted five phone interviews with culturally and linguistically diverse employees in southwest Kansas to understand COVID-19 knowledge, attitudes, and practices and communication preferences. Our experience details the potential challenges of the federal government in recruiting individuals from these communities and highlights the possibilities for more effectively engaging health department and community partners to support investigation efforts. Optimizing recruitment strategies with additional participation from community partners, developing culturally and linguistically appropriate data collection tools, and providing supportive resources and services may augment participation from refugee, immigrant, and migrant (RIM) communities in similar remote investigations.

Multistate Outbreak of Melioidosis Associated with Imported Aromatherapy Spray.

Melioidosis, caused by the bacterium Burkholderia pseudomallei, is an uncommon infection that is typically associated with exposure to soil and water in tropical and subtropical environments. It is rarely diagnosed in the continental United States. Patients with melioidosis in the United States commonly report travel to regions where melioidosis is endemic. We report a cluster of four non-travel-associated cases of melioidosis in Georgia, Kansas, Minnesota, and Texas. These cases were caused by the same strain of B. pseudomallei that was linked to an aromatherapy spray product imported from a melioidosis-endemic area.

Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence and Reported Coronavirus Disease 2019 Cases in US Children, August 2020-May 2021.

BACKGROUND: Case-based surveillance of pediatric coronavirus disease 2019 (COVID-19) cases underestimates the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among children and adolescents. Our objectives were to estimate monthly SARS-CoV-2 antibody seroprevalence and calculate ratios of SARS-CoV-2 infections to reported COVID-19 cases among children and adolescents in 8 US states. METHODS: Using data from the Nationwide Commercial Laboratory Seroprevalence Survey, we estimated monthly SARS-CoV-2 antibody seroprevalence among children aged 0-17 years from August 2020 through May 2021. We calculated and compared cumulative incidence of SARS-CoV-2 infection extrapolated from population-standardized seroprevalence of antibodies to SARS-CoV-2, cumulative COVID-19 case reports since March 2020, and infection-to-case ratios among persons of all ages and children aged 0-17 years for each state. RESULTS: Of 41 583 residual serum specimens tested, children aged 0-4, 5-11, and 12-17 years accounted for 1619 (3.9%), 10 507 (25.3%), and 29 457 (70.8%), respectively. Median SARS-CoV-2 antibody seroprevalence among children increased from 8% (range, 6%-20%) in August 2020 to 37% (range, 26%-44%) in May 2021. Estimated ratios of SARS-CoV-2 infections to reported COVID-19 cases in May 2021 ranged by state from 4.7-8.9 among children and adolescents to 2.2-3.9 for all ages combined. CONCLUSIONS: Through May 2021 in selected states, the majority of children with serum specimens included in serosurveys did not have evidence of prior SARS-CoV-2 infection. Case-based surveillance underestimated the number of children infected with SARS-CoV-2 more than among all ages. Continued monitoring of pediatric SARS-CoV-2 antibody seroprevalence should inform prevention and vaccination strategies.

Advances in Membrane Distillation Module Configurations.

Membrane Distillation (MD) is a membrane-based, temperature-driven water reclamation process. While research emphasis has been largely on membrane design, upscaling of MD has prompted advancements in energy-efficient module design and configurations. Apart from the four conventional configurations, researchers have come up with novel MD membrane module designs and configurations to improve thermal efficiency. While membrane design has been the focus of many studies, development of appropriate system configurations for optimal energy efficiency for each application has received considerable attention, and is a critical aspect in advancing MD configurations. This review assesses advancements in modified and novel MD configurations design with emphasis on the effects of upscaling and pilot scale studies. Improved MD configurations discussed in this review are the material gap MD, conductive gap MD, permeate gap MD, vacuum-enhanced AGMD/DCMD, submerged MD, flashed-feed MD, dead-end MD, and vacuum-enhanced multi-effect MD. All of these modified MD configurations are designed either to reduce the heat loss by mitigating the temperature polarization or to improve the mass transfer and permeate flux. Vacuum-enhanced MD processes and MD process with non-contact feed solution show promise at the lab-scale and must be further investigated. Hollow fiber membrane-based pilot scale modules have not yet been sufficiently explored. In addition, comparison of various configurations is prevented by a lack of standardized testing conditions. We also reflect on recent pilot scale studies, ongoing hurdles in commercialization, and niche applications of the MD process.

Agroinfiltration Mediated Scalable Transient Gene Expression in Genome Edited Crop Plants.

Agrobacterium-mediated transformation is one of the most commonly used genetic transformation method that involves transfer of foreign genes into target plants. Agroinfiltration, an Agrobacterium-based transient approach and the breakthrough discovery of CRISPR/Cas9 holds trending stature to perform targeted and efficient genome editing (GE). The predominant feature of agroinfiltration is the abolishment of Transfer-DNA (T-DNA) integration event to ensure fewer biosafety and regulatory issues besides showcasing the capability to perform transcription and translation efficiently, hence providing a large picture through pilot-scale experiment via transient approach. The direct delivery of recombinant agrobacteria through this approach carrying CRISPR/Cas cassette to knockout the expression of the target gene in the intercellular tissue spaces by physical or vacuum infiltration can simplify the targeted site modification. This review aims to provide information on Agrobacterium-mediated transformation and implementation of agroinfiltration with GE to widen the horizon of targeted genome editing before a stable genome editing approach. This will ease the screening of numerous functions of genes in different plant species with wider applicability in future.

The Prevalence of Diagnosis of Major Eye Diseases and their Associated Payments in the Medicare Fee-for-Service Program.

PURPOSE: To estimate the prevalence of diagnosis of major eye disorders and their associated payments, in total and per-person diagnosed, among Medicare fee-for-service (FFS) beneficiaries in 2018. METHODS: We analyzed 100% Medicare Part B FFS claims and Part D Events among beneficiaries continuously enrolled for 12 months in 2018 to calculate the proportion of beneficiaries with ≥1 claim indicating age-related macular degeneration (AMD), cataract, diabetic retinopathy (DR), or glaucoma, and their associated payments, including Medicare and patient out-of-pocket. Eye disease and eye care services were identified using case definitions from the Centers for Disease Control and Prevention's (CDC) Vision & Eye Health Surveillance System (VEHSS). Outcomes are reported by disease overall and by age group (0-39, 40-64, 65-84, 85+ years), sex, race/ethnicity, and U.S. state. RESULTS: Among nearly 30 million Medicare Part B FFS beneficiaries in 2018, over 41% (12.4 million) had a claim containing a diagnosis of at least one of the four eye disorders; 33.7% with cataract, 13.3% with glaucoma, 9.2% with AMD and 3.2% with DR. Payments for eye care services and drugs associated with these four conditions were $10.1billion; $3.6 billion for cataract, $3.5 billion for AMD, $2.2 billion for glaucoma and $0.8 billion for DR. The average cost per beneficiary diagnosed was $816: $1,290 for AMD, $781 for DR, $543 for glaucoma, and $360 for cataract. CONCLUSIONS: Major eye disorders are common among Medicare FFS beneficiaries and account for approximately 4.3% of Medicare Part B and 1% of Medicare Part D spending.