Personal Identification Number Research Articles

#1923 Anticoagulation and risk of stroke in patients with incident atrial fibrillation and CKD stages 4-5—results from the nationwide FinACAF study

Abstract Background and Aims Atrial fibrillation (AF) is common in patients with chronic kidney disease (CKD). It is well known that CKD in AF patients increases the risk of thromboembolic complications, and also bleeding. However, there is lack of safety and efficacy data of oral anticoagulation (OAC) in patients with advanced CKD. Method The FinACAF study includes data from 411 000 patients covering all Finnish AF patients from 2004 to 2018. Using national unique personal identification numbers, individual patients’ data from several registries and laboratory databases were linked together. The inclusion criteria of this study were all patients 20 years or older with a new-onset, non-valvular AF between 2010 and 2018 and a measured estimated glomerular filtration rate (eGFR) within the proximity of the AF diagnosis. Risk of stroke in patients with CKD stages 4-5 (eGFR < 30 ml/min/1.73 m2) was evaluated. Patients on dialysis and those with functioning graft were excluded. Participants were followed for the occurrence of ischemic stroke (IS) until December 31st 2018 or until death or until the OAC exposure reached a maximum duration of 730 days, whichever came first. The follow-up period was capped at 730 days due to the limited number of patients with direct oral anticoagulation (DOAC) exposure exceeding 730 days. Hazard ratios [95% confidence intervals (CI)] comparing different OACs or no OAC were derived from the Cox regression model. Results The study cohort included 4148 patients. The mean (SD) eGFR was 21.5 (6.7) ml/min/1.73 m2. 1940 patients had no OAC, 1658 patients had warfarin and 550 patients had any DOAC (396 apixaban, 121 rivaroxaban, 17 dabigatran and 16 edoxaban). During the follow-up 146 patients (3.5%) had ischemic stroke. Compared to patients with no OAC (reference) HRs were 0.42 [95% CI 0.30-0.59)] for the patients with warfarin and 0.28 [95% CI 0.01-0.52)] for the patients with DOACs. Cumulative hazards for ischemic stroke are shown in the Figure. Conclusion Among patients with incident AF and advanced CKD, the risk of stroke was lowest in patients with DOACs and the worst in patients with no OAC. Warfarin users were positioned in between these two groups. Further analysis is needed to evaluate also the safety of different OACs in our cohort.

#1000 Living alone and prognosis in elderly patients with chronic kidney disease: a nationwide study from Denmark

Abstract Background and Aims Patient care is increasingly relying upon involvement of patient relatives, including for patients with chronic kidney disease (CKD). However, patients living alone may be disadvantaged due to a lack of support. We aimed to assess the difference in prognosis after incident CKD in elderly patients between patients living alone versus living with others in a nationwide cohort study. Method We identified all patients aged 65 years or older with incident CKD from January 1, 2016, to December 31, 2020, with follow-up until December 31, 2021. We used data from national registries to identify CKD from out-patient creatinine measurements and linked these data to hospital treatment procedures and information from the Civil Person Registration system by the universal and unique personal identification number assigned to all Danish residents at birth or immigration. We defined incident CKD as having two or more estimated glomerular filtration rate (eGFR) values below 60 ml/min/1.73 m2 registered at least 90 days apart. We categorized eGFR according to “Kidney Disease: Improving Global Outcomes” (KDIGO) CKD stages into 45-59 ml/min/1.73 m2 (mildly/moderately decreased), 30-44 ml/min/1.73 m2 (moderately/severely decreased), 15-29 ml/min/1.73 m2 (severely decreased), <15 ml/min/1.73 m2 (kidney failure). We assessed cohabitation (living alone, or living with others), also in national registry data. We described the population by age group, sex and stage of CKD. Analyzing mortality, we followed patients from date of CKD to death or end of follow-up, whichever came first. We calculated the median time to death, using age as the time scale and reported these by cohabitation status with 95% confidence intervals (CIs). In further analyses, we will estimate the cumulated proportion who experienced a rapid decline in kidney function, as a measure of prognosis, and model the association between cohabitation and prognosis/mortality in regression models. Results We identified 204 662 elderly patients with CKD from 2016 to 2020, with 55% women and 38% 80 years or older. For severity, 84% had mildly/moderately decreased kidney function, 13% had moderately/severely decreased kidney function, 2% had severely decreased kidney function and only less than 1% (457 patients) presented with kidney failure. At index, 55% lived with others and 45% lived alone. Overall, 53 715 died during follow-up, and median age at death was 82 (95% CI: 82;82) for CKD patients living together with someone, but 78 (95% CI: 77;78) for those living alone. Conclusion The results are preliminary, and further analyses, including age adjustment, mortality estimates and information on adult children, will be available for presentation at the ERA conference 2024.

Gout and Gout-Related Comorbidities: Insight and Limitations from Population-Based Registers in Sweden

Population-based databases in Nordic countries offer unique opportunities for large-scale population-based epidemiological studies. The personal identity number enables researchers to link different registers at the individual level, which can be used for large-scale epidemiological population-based studies. This review outlines how these opportunities have been used so far in the field of gout research, as well as the potential challenges and limitations. Their major advantage is that they cover the entire population, minimizing problems such as selection bias and loss to follow-up. This has enabled us to provide information on gout regarding risk factors; occurrence; association with comorbidities in relation to gout onset; treatment patterns; as well as its effect on other outcomes, such as sick leave and mortality. Validity issues, missing data, and legal issues are some of the challenges that researchers need to deal with. Choosing the most appropriate combination of databases to use for a specific question is crucial in order to maximize validity and adjust for confounders. Despite challenges and potential limitations, the Swedish registers have provided valuable epidemiological results and will continue to play an important role in the years to come.

Exploring End-of-Life Care for Patients with Breast Cancer, Dementia or Heart Failure: A Register-Based Study of Individual and Institutional Factors.

To examine variations in end-of-life care for breast cancer, heart failure, and dementia patients. Data from four Norwegian health registries were linked using a personal identification number. Longitudinal trends over 365 days and the type of care on the final day of life were analyzed using descriptive techniques and logistic regression analysis. Patients with dementia were more commonly placed in nursing homes than patients in the two other groups, while patients with heart failure and breast cancer were more frequently hospitalized than the dementia patients. Breast cancer and heart failure patients had a higher likelihood of dying at home than dementia patients. The higher the number of general practitioners, the higher was the probability of home-based end-of-life care for cancer patients, while an increasing non-physician healthcare workers increased the likelihood of home-based care for the other patient groups. Diagnoses, individual characteristics, and service availability are all associated with the place of death in end-of-life care. The higher the availability of health care services, the higher also is the probability of ending the life at home.

Master Face Generation Using Latent Variable Evolution in Face Recognition System

Abstract: Face authentication is now widely used, especiallyon mobile devices, rather than authentication using a personal identification number or an unlock pattern, due to its convenience. It has thus become a tempting target for attackers using a presentation attack. Traditional presentationattacks use facial images or videos of the victim. Previous work has proven the existence of master faces, i.e., faces that matchmultiple enrolled templates in face recognition systems, and their existence extends the ability of presentation attacks. In this paper, we perform an extensive study on latent variable evolution (LVE), a method commonly used to generate master faces. We run an LVE algorithm for various scenarios and with more than one database and/or face recognition system tostudy the properties of the master faces and to understand inwhich conditions strong master faces could be generated. Moreover, through analysis, we hypothesize that master faces come from some dense areas in the embedding spaces of theface recognition systems. Last but not least, simulated presentation attacks using generated master faces generally preserve the false-matching ability of their original digital forms, thus demonstrating that the existence of master facesposes an actual threat.

Eye Based Secure Authentication System

Abstract: Personal identification numbers are commonly utilized for user verification and enhanced security. When users authenticate passwords through PINs, they must be obligatory to physically input the PIN, making them susceptible to password cracking techniques like shoulder surfing or thermal tracking. In contrast, utilizing hands-off gaze-based PIN entry methods eliminates any physical traces, providing a significantly more secure option for password entry. Gaze-based authentication involves determining the eye location across consecutive image frames and continuously tracking the precise eye center.

MORSE CODE-BASED AUTHENTICATION SYSTEM

To tackle analytically complex issues, data science is a multidisciplinary combination of data inference, algorithm development, and technology. Nearly every industry, including business, finance, healthcare, and education, uses data science to manage massive volumes of data. Practical uses include text prediction, image processing, identity recognition, audio processing for speech, stock movement, and cancer prediction. Given that the majority of individuals on the planet have issues with security and authentication, For those who use Morse Code for self-authentication, we can offer real-time eye tracing for password authentication. As we all know, the 21st century has seen significant support for advancements in authorization and authentication technology. Since the late 1990s, personal identification numbers, or PINs, have been extensively used for user authentication and security. These days, it is easy to crack PIN codes, so we would rather use a different strategy. On the other hand, PIN authentication using hands-off gaze-based PIN entry techniques offers a more secure password entry option because it leaves no physical traces behind. Key Words: Morse code, Face recognition, Pin Entry, Eye Blinks, Gaze based

Biometric ATM Authentication System

As technology progresses, traditional authentication methods like Personal Identification Numbers (PINs) and passwords are becoming more prone to security breaches. To address this issue, biometric-based authentication systems are being seen as a reliable solution to boost security in different areas, such as Automated Teller Machines (ATMs). This study delves into the deployment, advantages, obstacles, and future potential of a biometric-based ATM system. By examining current research, real-life examples, and technological innovations, the aim of this paper is to shed light on the efficiency and viability of biometric authentication in ATM systems. Key Words: Enhanced Security, Authentication, Efficiency, Reliability

Incidence of sick leave and disability pension in adults with musculoskeletal pain and co-occurring long-term conditions: data from the Norwegian HUNT study and national registries

BackgroundMusculoskeletal pain is one of the leading causes of work productivity loss. Long-term conditions (LTCs) commonly occur alongside musculoskeletal pain. However, the incidence of sick leave and disability pension according to LTC status in people with musculoskeletal pain has not been previously described.MethodsWorking-age participants (20–65 years) with persistent musculoskeletal pain who participated in the HUNT3 Study (1995–97) were included. Twenty-five LTCs were classified into 8 LTC groups according to the International Classification of Diseases version 11. Data on sickness and disability benefits were obtained from the National Insurance Database and linked to the HUNT3 data using participants’ personal identification number. Age-adjusted incidence rates (IRs) (per 10,000 person-years) and hazard ratios (HRs) of sick leave during 5-year follow-up and disability pension during ~ 25-year follow-up were estimated with 95% confidence intervals (CIs) and presented according to LTC status.ResultsOverall, 11,080 participants with musculoskeletal pain were included. Of those, 32% reported one LTC and 45% reported ≥ 2 LTCs. During the follow up period, 1,312 participants (12%) received disability pension due to musculoskeletal conditions. The IR of sick leave and disability pension due to musculoskeletal conditions increased with number of LTCs. Specifically, the IR of sick leave was 720 (95% CI 672 to 768) in participants without any LTCs and 968 (95% CI 927 to 1,009) if they had ≥ 2 LTCs. The IRs of disability pension were 87 (95% CI 75 to 98) and 167 (95% CI 154 to 179) among those with no LTCs and ≥ 2 LTCs, respectively. The incidence of sick leave and disability pension due to musculoskeletal conditions was largely similar across LTCs, although the incidence of disability pension was somewhat higher among people with sleep disorders (IR: 223, 95% CI 194 to 252).ConclusionsAmong people with persistent musculoskeletal pain, the incidence of prematurely leaving the work force due to musculoskeletal conditions was twice as high for those with multiple LTCs compared to those without any LTCs. This was largely irrespective of the type of LTC, indicating that the number of LTCs are an important feature when evaluating work participation among people with musculoskeletal pain.

Effect of a national infection control programme in Sweden on prosthetic joint infection incidence following primary total hip arthroplasty: a cohort study

ObjectivesProsthetic joint infection (PJI) is a serious complication following total hip arthroplasty (THA) entailing increased mortality, decreased quality of life and high healthcare costs.The primary aim was to investigate whether...

The Danish Aging and Cognition (DanACo) cohort

BackgroundWith aging populations worldwide, identification of predictors of age-related cognitive decline is becoming increasingly important. The Danish Aging and Cognition Cohort (DanACo) including more than 5000 Danish men was established to investigate predictors of age-related cognitive decline from young adulthood to late mid-life.Construction and contentThe DanACo cohort was established through two separate data collections with identical designs involving a follow-up examination in late mid-life of men for whom intelligence test scores were available from their mandatory conscription board examination. The cohort consists of 5,183 men born from 1949 through 1961, with a mean age of 20.4 years at baseline and a mean age of 64.4 years at follow-up. The baseline measures consisted of height, weight, intelligence test score and educational level collected at the conscription board examination. The follow-up assessment consisted of a re-administration of the same intelligence test and a comprehensive questionnaire covering socio-demographic factors, lifestyle, and health-related factors. The data were collected in test sessions with up to 24 participants per session. Using the unique personal identification number assigned to all Danes, the cohort has been linked to data from national administrative and health registers for prospectively collected data on socioeconomic and health-related factors.Utility and discussionThe DanACo cohort has some major strengths compared to existing cognitive aging cohorts such as a large sample size (n = 5,183 men), a validated global measure of cognitive ability, a long retest interval (mean 44.0 years) and the availability of prospectively collected data from registries as well as comprehensive questionnaire data. The main weakness is the low participation rate (14.3%) and that the cohort consists of men only.ConclusionCognitive decline is a result of a summary of factors across the life-course. The DanACo cohort is characterized by a long retest interval and contains data on a wealth of factors across adult life which is essential to establish evidence on predictors of cognitive decline. Moreover, the size of the cohort ensures sufficient statistical power to identify even relatively weak predictors of cognitive decline.

Neonatal Outcomes After COVID-19 Vaccination in Pregnancy

Better knowledge about neonatal adverse events after COVID-19 vaccination during pregnancy could help address concerns about vaccine safety. To evaluate the risks of neonatal adverse events after exposure to COVID-19 vaccination during pregnancy. Population-based cohort study including all infants in Sweden and Norway born from June 2021 to January 2023. Unique personal identity numbers were used to link individual information from different national registers. Administration of any mRNA vaccine against COVID-19 during pregnancy, irrespective of previous vaccination, number of doses during pregnancy, or vaccine manufacturer. Outcomes were neonatal conditions with bleeding/thrombosis or inflammation/infection; disorders of the central nervous system; circulatory, respiratory, or gastrointestinal problems; and neonatal mortality. Statistical methods included logistic regression adjusted for characteristics of the pregnant individuals, with additional restricted and stratified analyses. Of 196 470 newborn infants included (51.3% male, 93.8% born at term, 62.5% born in Sweden), 94 303 (48.0%) were exposed to COVID-19 vaccination during pregnancy. Exposed infants exhibited no increased odds of adverse neonatal outcomes, and they exhibited lower odds for neonatal nontraumatic intracranial hemorrhage (event rate, 1.7 vs 3.2/1000; adjusted odds ratio [aOR], 0.78 [95% CI, 0.61-0.99]), hypoxic-ischemic encephalopathy (1.8 vs 2.7/1000; aOR, 0.73 [95% CI, 0.55-0.96]), and neonatal mortality (0.9 vs 1.8/1000; aOR, 0.68 [95% CI, 0.50-0.91]). Subgroup analyses found a similar association between vaccination during pregnancy and lower neonatal mortality; subgroups were restricted to infants delivered by individuals unvaccinated before pregnancy, individuals vaccinated before pregnancy, individuals vaccinated after a general recommendation of vaccination during pregnancy was issued, and individuals without COVID-19 infection during pregnancy. Analyses restricted to term infants, singleton births, or infants without birth defects yielded similar results. Stratifying the analysis by vaccine manufacturer did not attenuate the association between vaccination and low neonatal mortality. In this large population-based study, vaccination of pregnant individuals with mRNA COVID-19 vaccines was not associated with increased risks of neonatal adverse events in their infants.

A Review on Palm Vein Recognition using Deep Neural Network

The expansion of the internet has significantly in- creased the use of internet data, which necessitates security through unique identity. Traditional security mechanisms, such as user credentials and personal identification numbers (PINs), failed to meet user’s demands. Hence a unique identification mechanism is required to offer excellent security for the data. Bio- metrics plays a vital role in today’s authentication and recognition in various situations. Biometrics is concerned with the study of specific behavioral and physical characteristics. Fingerprint, face, iris/ retinal, voice, and vascular authentication are some of the biometric modalities that are used for identification. In this paper, different procedures involving palm vein recognition and authentication are discussed

When Numbers Run Out

In the early 2000s, authorities in Sweden and Denmark recognised that their personal identification numbers were about to run out but followed different interventions to resolve the same issue. In this paper, I start from these cases to analyse personal identification numbers as methods for knowing and governing populations. I draw on two assertions from the study of methods within STS: Methods are performative, and they produce multiple objects and realities. I demonstrate how such identification numbers enact individuals and populations simultaneously, and I identify a fundamental tension between them: one emphasising the representational potential of the part and another favouring the coherence of the whole. I conclude that issues surrounding personal identification numbers in use across all Nordic countries can be traced back to a fundamental tension in addressing individuals that is impossible to resolve via technical fixes, although those interventions are crucial to keeping the systems operational.

Incidence and case ascertainment of treated in-hospital cardiac arrest events in a national quality registry – A comparison of reported and non-reported events

BackgroundApproximately 2500 in-hospital cardiac arrest (IHCA) events are reported annually to the Swedish Registry of Cardiopulmonary Resuscitation (SRCR) with an estimated incidence of 1.7/1000 hospital admissions. The aim of this study was to evaluate the compliance in reporting IHCA events to the SRCR and to compare reported IHCA events with possible non-reported events, and to estimate IHCA incidence. MethodsFifteen diagnose codes, eight Classification of Care Measure codes, and two perioperative complication codes were used to find all treated IHCAs in 2018–2019 at six hospitals of varying sizes and resources. All identified IHCA events were cross-checked against the SRCR using personal identity numbers. All non-reported IHCA events were retrospectively reported and compared with the prospectively reported events. ResultsA total of 3638 hospital medical records were reviewed and 1109 IHCA events in 999 patients were identified, with 254 of the events not found in the SRCR. The case completeness was 77% (range 55–94%). IHCA incidence was 2.9/1000 hospital admissions and 12.4/1000 admissions to intensive care units. The retrospectively reported events were more often found on monitored wards, involved patients who were younger, had less comorbidity, were often found in shockable rhythm and more often achieved sustained spontaneous circulation, compared with in prospectively reported events. ConclusionIHCA case completeness in the SRCR was 77% and IHCA incidence was 2.9/1000 hospital admissions. The retrospectively reported IHCA events were found in monitored areas where the rapid response team was not alerted, which might have affected regular reporting procedures.

Epidemiology of patients assessed for trauma by Swedish ambulance services: a retrospective registry study

BackgroundThere is a lack of knowledge regarding the epidemiology of severe trauma assessed by Swedish emergency medical services (EMS).AimTo investigate the prevalence of trauma in Sweden assessed by EMS from a national perspective and describe patient demography, aetiology, trauma type, prehospital triage and clinical outcomes.MethodsData from two national quality registries, the Swedish Ambulance Registry and the Swedish Trauma Registry (SweTrau) were collected from January 1 to December 31, 2019. Inclusion criteria were an Emergency Symptoms and Signs code equivalent to trauma in the Swedish Ambulance Registry and criteria fulfilled for SweTrau inclusion. Exclusion criteria were patients < 18 years old, those not transported to a hospital and those without a personal identification number.ResultsIn total, 53,120 patients with trauma were included (14% of primary EMS missions involving a personal identification number). Of those, 2,278 (4.3%) patients (median age: 45 years; 32% women) were reported in SweTrau to have severe or potentially severe trauma (penetrating: 7%, blunt: 93%). In terms of including all causes of trauma, the code for ‘trauma alert activation’ was most frequent (55%). The most frequent injury mechanism was an injury caused by a car (34%). Most (89%) cases were assigned Priority 1 (life-threatening condition) at the dispatch centre. 62% were regarded as potentially life threatening upon EMS arrival, whereas 29% were assessed as non-life-threatening. Overall, 25% of the patients had new injury severity scores > 15. 12% required invasive treatment, 11% were discharged with severe disability and the 30-day mortality rate was 3.6%.ConclusionIn this cross-sectional study, 14% of the primary EMS missions for one year were caused by trauma. However, only a small proportion of these cases are severe injuries, and the risk of severe disabilities and death appears to be limited. The most frequent aetiology of a severe trauma is injury caused by a car, and most severe traumas are blunt. Severe traumas are given the highest priority at the dispatch centre in the vast majority of cases, but nearly one-third of these cases are considered a low priority by the EMS nurse. The latter leaves room for improvement.

Does Personality Traits and Security Habits Influence Security of Personal Identification Numbers? The Context of Mobile Money Services in Tanzania.

Does Personality Traits and Security Habits Influence Security of Personal Identification Numbers? The Context of Mobile Money Services in Tanzania.

Key Features of Smart Medication Adherence Products: Updated Scoping Review.

Older adults often face challenges in self-managing their medication owing to physical and cognitive limitations, complex medication regimens, and packaging of medications. Emerging smart medication dispensing and adherence products (SMAPs) offer the options of automated dispensing, tracking medication intake in real time, and reminders and notifications. A 2021 review identified 51 SMAPs owing to the rapid influx of digital technology; an update to this review is required. This review aims to identify new products and summarize and compare the key features of SMAPs. Gray and published literature and videos were searched using Google, YouTube, PubMed, Embase, and Scopus. The first 10 pages of Google and the first 100 results of YouTube were screened using 4 and 5 keyword searches, respectively. SMAPs were included if they were able to store and allowed for the dispensation of medications, tracked real-time medication intake data, and could automatically analyze data. Products were excluded if they were stand-alone software applications, not marketed in English, not for in-home use, or only used in clinical trials. In total, 5 researchers independently screened and extracted the data. This review identified 114 SMAPs, including 80 (70.2%) marketed and 34 (29.8%) prototypes, grouped into 15 types. Among the marketed products, 68% (54/80) were available for consumer purchase. Of these products, 26% (14/54) were available worldwide and 78% (42/54) were available in North America. There was variability in the hardware, software, data collection and management features, and cost of the products. Examples of hardware features include battery life, medication storage capacity, availability of types and number of alarms, locking features, and additional technology required for use of the product, whereas software features included reminder and notification capabilities and availability of manufacturer support. Data capture methods included the availability of sensors to record the use of the product and data-syncing capabilities with cloud storage with short-range communications. Data were accessible to users via mobile apps or web-based portals. Some SMAPs provided data security assurance with secure log-ins (use of personal identification numbers or facial recognition), whereas other SMAPs provided data through registered email addresses. Although some SMAPs were available at set prices or free of cost to end users, the cost of other products varied based on availability, shipping fees, and subscription fees. An expanding market for SMAPs with features specific to at-home patient use is emerging. Health care professionals can use these features to select and suggest products that meet their patients' unique requirements.

Met and unmet prison-based treatment needs for people who are incarcerated with a history of substance use disorder: A nationwide cohort study

BackgroundSubstance use disorders (SUD) are highly prevalent among incarcerated people. However, in some prisons, only a small percentage of those who need treatment receive it. The aims of this study were to examine coverage of treatment for SUD in Danish prisons and assess whether treatment differed by substance class. Further, we examined factors associated with receiving treatment for SUD, and types of services received. Data and methodsWe linked multiple Danish register data using unique personal identification numbers. This study retrospectively analysed data for 49,330 individuals (aged 18–90) incarcerated in Danish prisons between 2008 and 2018. We used a multivariable logistic regression model to predict enrolment in treatment for SUD in prison. ResultsOf incarcerated people with a history of SUD, 34.6 % received treatment care during incarceration. We observed only minor variations in terms of substance classes concerning the type of treatment. Those who were women, immigrants, had higher education, or were married were less likely to receive treatment. ConclusionsImproving access and increasing treatment coverage in the Danish Prison and Probation Services is crucial to reduce the burden of SUD in incarcerated populations.

Design Smart Door Locks With Internet Of Things Based On Pin Security Features

Smart door lock systems have become an interesting topic of research in recent years due to the need for higher security when accessing rooms or buildings. This research aims to design and implement a smart door lock system that uses an Internet of Things (IoT)-based personal identification number (PIN) that can be controlled through the Telegram messaging platform.&#x0D; The system is designed so that users can give commands via Telegram messages to open or lock doors securely. Users can access the door without needing to be physically near it. In addition, the level of security is enhanced by allowing only authorized users to control the door via Telegram messages, as well as by implementing strong encryption and authentication mechanisms.&#x0D; In conclusion, this study succeeded in designing and implementing an IoT-based smart door lock system that can be controlled through the Telegram messaging platform using a personal identification number (PIN) as a security method. This system provides an efficient, secure, and practical solution for managing smart door access remotely. It is expected that this research can make a positive contribution to the development of smart door security technology and IoT applications at large