The Pattern of Admission, Clinical Characteristics, and Outcomes Among Patients Admitted to the Intensive Care Unit of a Tertiary Hospital in Tanzania: A 5-Year Retrospective Review.

Introduction: Despite the implementation of complex interventions, ICU mortality remains high and more so in developing countries. The demand for critical care in Sub-Saharan Africa is more than ever before as the region experiences a double burden of rising rates of non-communicable diseases (NCD) in the background battle of combating infectious diseases. Limited studies in Tanzania have reported varying factors associated with markedly high rates of ICU mortality. Investigating the burden of ICU care remains crucial in providing insights into the effectiveness and challenges of critical care delivery. Material and Methods: A single-center retrospective study that reviewed records of all medically admitted patients admitted to the ICU of the Aga Khan Hospital, Dar-es-Salaam, from 1st October 2018 to 30th April 2023. To define the population in the study, we used descriptive statistics. Patients' outcomes were categorized based on ICU survival. Binary logistic regression was run (at 95% CI and p-value < 0.05) to identify the determinants for ICU mortality. Results: Medical records of 717 patients were reviewed. The cohort was male (n=472,65.8%) and African predominant (n=471,65.7%) with a median age of 58 years (IQR 45.0-71.0). 17.9% of patients did not survive. The highest mortality was noted amongst patients with septic shock (29.3%). The lowest survival was noted amongst patients requiring three organ support (n=12,2.1%). Advanced age (OR 1.02,CI 1.00-1.04), having more than three underlying comorbidities (OR 2.50,CI 1.96-6.60), use of inotropic support (OR 3.58,CI 1.89-6.80) and mechanical ventilation (OR 9.11,CI 4.72-18.11) showed association with increased risk for mortality in ICU. Conclusion: The study indicated a much lower ICU mortality rate compared to similar studies conducted in other parts of Sub-Saharan Africa. Advanced age, underlying multiple comorbidities and organ support were associated with ICU mortality. Large multi-center studies are needed to highlight the true burden of critical care illness in Tanzania.

A private hospital's approach to treating acute familial Mediterranean fever in Dar es Salaam.

Familial Mediterranean fever is a rare autosomal recessive autoinflammatory disorder prevalent in Middle Eastern populations, characterized by episodic abdominal pain. This case report presents a 34-year-old Egyptian man with severe lower abdominal pain, chest discomfort, and joint pain, along with a positive family history of familial Mediterranean fever but had no previous personal history of this condition. Blood work revealed leukocytosis with neutrophilia and elevated C-reactive protein and erythrocyte sedimentation rate. The patient received intravenous fluids, antiemetics, and analgesics before further evaluation. Diagnosis of familial Mediterranean fever relies on clinical symptoms, ethnic origin, and family history, supported by specific criteria. Typical familial Mediterranean fever attacks involve serositis-induced pain, recurrent episodes, short-duration fever (12 h to 3 days), and arthritis. Familial Mediterranean fever may mimic other acute abdominal conditions, warranting consideration, particularly in individuals from Mediterranean regions. Genetic testing is valuable in confirming familial Mediterranean fever diagnosis.

Recent Advances in Smart Epidural Spinal Needles.

Lumbar puncture is a minimally invasive procedure that utilizes a spinal needle to puncture the lumbar epidural space to take a sample from the cerebrospinal fluid or inject drugs for diagnostic and therapeutic purposes. Physicians rely on their expertise to localize epidural space. Due to its critical procedure, the failure rate can reach up to 28%. Hence, a high level of experience and caution is required to correctly insert the needle without puncturing the dura mater, which is a fibrous layer protecting the spinal cord. Failure of spinal anesthesia is, in some cases, related to faulty needle placement techniques since it is blindly inserted. Therefore, advanced techniques for localization of the epidural space are essential to avoid any possible side effects. As for epidural space localization, various ideas were carried out over recent years to provide accurate identification of the epidural space. Subsequently, several methodologies based on mechanical and optical schemes have been proposed. Several research groups worked from different aspects of the problem, namely, the clinical and engineering sides. Hence, the main goal of this paper is to review this research with the aim of remedying the gap between the clinical side of the problem and the engineering side by examining the main techniques in building sensors for such purposes. This manuscript provides an understanding of the clinical needs of spinal needles from an anatomical point of view. Most importantly, it discusses the mechanical and optical approaches in designing and building sensors to guide spinal needles. Finally, the standards that must be followed in building smart spinal needles for approval procedures are also presented, along with some insight into future directions.

Magnitude, Distribution and Contextual Risk Enhancing Predictors of High 10-Year Cardiovascular Risk Among Diabetic Patients in Tanzania.

Introduction: Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of death worldwide. In Diabetics, ASCVD is associated with poor prognosis and a higher case fatality rate compared with the general population. Sub-Saharan Africa is facing an epidemiological transition with ASCVD being prevalent among young adults. To date, over 20 million people have been living with DM in Africa, Tanzania being one of the five countries in the continent reported to have a higher prevalence. This study aimed to identify an individual's 10-year ASCVD absolute risk among a diabetic cohort in Tanzania and define contextual risk enhancing factors. Methods: A prospective observational study was conducted at the Aga Khan hospital, Mwanza, for a period of 8 months. The hospital is a 42-bed district-level hospital in Tanzania. Individuals 10-year risk was calculated based on the ASCVD 2013 risk calculator by ACC/AHA. Pearson's chi-square or Fischer's exact test was used to compare categorical and continuous variables. Multivariable analysis was applied to determine contextual factors for those who had a high 10-year risk of developing ASCVD. Results: The overall cohort included 573 patients. Majority of the individuals were found to be hypertensive (n = 371, 64.7%) and obese (n = 331, 58%) having a high 10-year absolute risk (n = 343, 60%) of suffering ASCVD. The study identified duration of Diabetes Mellitus (>10 years) (OR 8.15, 95% CI 5.25-14.42), concomitant hypertension (OR 1.82 95% CI 1.06-3.06), Diabetic Dyslipidemia (OR 1.44, 95% CI 1.08-1.92) and deranged serum creatinine (OR 1.03, 95% CI 1.02-1.03) to be the risk enhancing factors amongst our population. Conclusion: The study confirms the majority of diabetic individuals in the lake region of Tanzania to have a high 10-year ASCVD risk. The high prevalence of obesity, hypertension and dyslipidemia augments ASCVD risk but provides interventional targets for health-care workers to decrease these alarming projections.

Evaluation of venous thromboembolism (VTE) risk assessment and thrombo-prophylaxis practices in hospitalized medical and surgical patients at Aga Khan Hospital Dar es Salaam: single-centre retrospective study.

Introduction: venous thromboembolism is a complication among admitted medical and surgical patients. International guidelines recommend patients are assessed upon admission and appropriate thromboprophylaxis should be initiated. However, studies have shown that thromboprophylaxis for patients at risk of venous thromboembolism is underutilized. Methods: this was a retrospective study conducted on hospitalized medical and surgical patients at Aga Khan Hospital Dar es salaam from January to June 2019. Patient's medical records were reviewed and data was collected for analysis of venous thromboembolism assessment and compliance with Caprini risk assessment model. The data was entered into statistical package for the social sciences (SPSS) 25 and categorized into risk groups, frequency of patients' demographic and clinical characteristics data was calculated and the main study outcomes were analyzed with Fisher´s exact test or Pearson chi-square test for categorical variables and student t-test for continuous variables. Regression analyses were done to identify significant risk factors where by P ≤ 0.05 was considered statistically significant. Results: compliance of venous thromboembolism assessment among medical and surgical patients was similar at 78% and 80%, respectively, with a baseline 22% of all admitted patients considered at risk of venous thromboembolism, hence needing thromboprophylaxis following the Caprini risk assessment modelscore. Thromboprophylaxis practices was identified at just 25% of at-risk individuals received pharmacological prophylaxis with enoxaparin; the most commonly used agent (92%). Identified risk factors for venous thromboembolism were advancing age (>60 years), history of prior major surgery, Major surgery lasting > 60 minutes, obesity, and immobilization. Conclusion: risk assessment for venous thromboembolism should be emphasized upon admission of both surgical and medical patients. Adequate thromboprophylaxis should be prescribed upon identification of patients at risk.

The cultural differences in the effects of carbon emissions - an EKC analysis.

The postmodernism stance critiques the current discourse of modern consumption-based societies. These societies legitimize their embedded beliefs and actions based on their lifestyle reflected through their consumption patterns. Their consumption patterns relate to carbon footprints that are yet to be explored in the current body of knowledge at the macro level. The legitimacy of their lifestyle and consumption patterns rely on their conscious efforts in reducing carbon footprints. This study uses the environmental Kuznets curve model and explores the impact of household lifestyle and household consumption patterns on CO2 emissions across different cultures and societies worldwide. 49 countries were taken to assess how different cultures define consumption patterns related to CO2 emission. The results showed that the curvilinear relationship between consumption and CO2 depends on the country's national cultural orientation.

Role of globalziation defining the incidence of entrepreneurship.

Globalization boosts the process of market predictions in the pursuit of economic growth. When economic, political, and social forces gain traction by promoting policies and the climate favoring globalization, entrepreneurial results reach out. Policymakers are still searching for a context within which regional policies can be structured to foster long-term entrepreneurship opportunities. The literature on entrepreneurial phenomena is incomplete and uncertain as to how globalization forces establish a nonlinear mechanism to promote the entrepreneurial process. This study provides the basic context for identifying globalization forces to create a nonlinear effect on the entrepreneurial process in order to address this problem. The results propose that policymakers strengthen the social and political dimension of globalization to increase opportunities-based entrepreneurship.

Outcomes of Surgical Tracheostomy on Mechanically Ventilated COVID-19 Patients Admitted to a Private Tertiary Hospital in Tanzania.

OBJECTIVES:  The coronavirus disease 2019 (COVID-19) pandemic has resulted in an increase in the number of patients necessitating prolonged mechanical ventilation. Data on patients with COVID-19 undergoing tracheostomy indicating timing and outcomes are very limited. Our study illustrates--- outcomes for surgical tracheotomies performed on COVID-19 patients in Tanzania. METHODS:  This was a retrospective observational study conducted at the Aga Khan Hospital in Dar es Salaam, Tanzania. RESULTS:  Nineteen patients with COVID-19 underwent surgical tracheotomy between 16th March and 31st December 2021. All surgical tracheostomies were performed in the operating theatre. The average duration of intubation prior to tracheotomy and tracheostomy to ventilator liberation was 16 days and 27 days respectively. Only five patients were successfully liberated from the ventilator, decannulated, and discharged successfully. CONCLUSIONS:  This is the first and largest study describing tracheotomy outcomes in COVID-19 patients in Tanzania. Our results revealed a high mortality rate. Multicenter studies in the private and public sectors are needed in Tanzania to determine optimal timing, identification of patients, and risk factors predictive of improved outcomes.

Factors Associated with Mortality Among Hospitalized Adults with COVID-19 Pneumonia at a Private Tertiary Hospital in Tanzania: A Retrospective Cohort Study.

BACKGROUND: The emergence of the novel coronavirus disease 2019 (COVID-19) has caused millions of deaths worldwide. There has been paucity of data for hospitalized African patients suffering from COVID-19. This study aimed to identify factors associated with in-hospital mortality in patients suffering from COVID-19 in Tanzania. METHODS: This was a single center, retrospective, observational cohort study in adult patients hospitalized with confirmed COVID-19 infection. Demographics, clinical pattern, laboratory and radiological investigations associated with increased odds of mortality were analyzed. RESULTS: Of the 157 patients, 107 (68.1%) patients survived and 50 (31.8%) died. Mortality was highest in patients suffering with severe (26%) and critical (68%) forms of the disease. The median age of the cohort was 52 years (IQR 42-61), majority of patients were male (86%) and of African origin (46%), who presented with fever (69%), cough (62%) and difficulty in breathing (43%). Factors that were associated with mortality among our cohort were advanced age (OR 1.07, 95% CI 1.03-1.11), being overweight and obese (OR 9.44, 95% CI 2.71-41.0), suffering with severe form of the disease (OR 4.77, 95% CI 1.18-25.0) and being admitted to the HDU and ICU (OR 6.68, 95% CI 2.06-24.6). CONCLUSION: The overall in-hospital mortality was 31.8%. Older age, obesity, the severe form of the disease and admission to the ICU and HDU were major risk factors associated with in-hospital mortality.

Case Report: Sudden Splenic Rupture in a Plasmodium falciparum-Infected Patient.

Spontaneous splenic rupture is a rare and life-threatening complication of severe malaria. It demands particular attention since delayed or missed diagnosis can be potentially fatal. The exact incidence is unknown largely due to underreporting. Acute malarial infection accounts for most of the spontaneous splenic rupture. Plasmodium vivax has been associated with the majority of them; however, on rare occasion, other Plasmodium infections have also resulted in splenic rupture. We report the case of a 74-year-old male who was diagnosed with severe malaria caused by Plasmodium falciparum (P. falciparum) infection and developed an acute abdomen while on treatment due to spontaneous splenic rupture which necessitated emergency splenectomy.

Hepatoprotective effects of ethanolic extract of Boerhaavia diffusa against oxaliplatin induced hepatotoxicity in albino rats.

The hepatoprotective effects of Boerhaavia diffusa was studied against the hepatotoxicity induced by oxaliplatin. Male Wistar rats were divided in three groups.Group N* control group (0.9% normal saline), Group NP0 oxaliplatin treated group and Group NP2 were prophylactically treated with Boerhaavia diffusa and then with oxaliplatin in order to assess the protective effects of Boerhaavia diffusa against the toxicity of oxaliplatin. The levels of liver enzymes ALT, AST and γ-GT were significantly reduced in the group prophylactically treated with Boerhaavia diffusa (NP2) compared with the group treated with oxaliplatin (NP0). Boerhaavia diffusa was effective in reducing risk of hypercholestremia associated with oxaliplatin. Histopathological examination of rat liver revealed that prophylactically treated group with Boerhaavia diffusa was effective in reducing oxidative stress induced steatohepatitis by oxaliplatin.

Assesment of predictor variables and clinical consequences associated with surgical site infection in tertiary care setting, Karachi, Pakistan.

Among the well-known Health care-associated infections (HAIs), surgical site infections (SSIs) contribute to considerable high mortality and morbidity rate, substantial prolongation in hospitalization period and extra expenses in terms of treatment cost. This study was aimed to evaluate the predictive variables associated with surgical site infections, and their clinical consequences. This was a prospective, cross sectional study conducted in the surgical department of tertiary care setting in Karachi, Pakistan. Each patient was followed up from the time of admission until time of the discharge postoperatively for 30 days. A total of 554 surgical procedures were performed and 81 SSIs were identified. The predictor variable/risk factors significantly associated with the presence of SSI were age, gender, BMI, ASA score, co-morbid condition, surgical wound class, emergency surgeries, duration of surgery, type of anesthesia, prosthetic implant, pre operative length of stay and pre operative blood transfusion. Outcomes of such studies may be utilized in the design of a multi factorial practice to get better patient's safety and clinical outcomes.

Diagnostic Accuracy of Ultrasound B scan using 10 MHz linear probe in ocular trauma;results from a high burden country.

OBJECTIVE: To study the diagnostic accuracy of Ultrasound B scan using 10 MHz linear probe in ocular trauma. METHODS: A total of 61 patients with 63 ocular injuries were assessed during July 2013 to January 2014. All patients were referred to the department of Radiology from Emergency Room since adequate clinical assessment of the fundus was impossible because of the presence of opaque ocular media. Based on radiological diagnosis, the patients were provided treatment (surgical or medical). Clinical diagnosis was confirmed during surgical procedures or clinical follow-up. RESULTS: A total of 63 ocular injuries were examined in 61 patients. The overall sensitivity was 91.5%, Specificity was 98.87%, Positive predictive value was 87.62 and Negative predictive value was 99%. CONCLUSION: Ultrasound B-scan is a sensitive, non invasive and rapid way of assessing intraocular damage caused by blunt or penetrating eye injuries.

DOES VITAMIN D DEFICIENCY CONTRIBUTE TO THE SEVERITY OF ASTHMA IN CHILDREN AND ADULTS?

Role of vitamin D in the health of bones has been well established for over decades; It was known that its deficiency caused rickets in children and osteomalacia in adults. Later it was discovered that these can be corrected by giving vitamin D. Researchers discovered that vitamin D can be synthesized by exposure to sun. Hence it was also named "the sunshine vitamin". As time passed it was observed that low levels of vitamin D were associated with multiple diseases. This sparked the interest of the scientific community to further the research on vitamin D which led to the studies that started associating vitamin D with various diseases like cancers (prostate, colon and breast), autoimmune diseases (rheumatoid arthritis), infectious diseases (tuberculosis, hepatitis B, hepatitis C, HIV), cardiovascular diseases, mental illnesses (schizophrenia), diabetes mellitus (type 1, type 2 and gestational) and allergic conditions like asthma. With time, more studies were carried out relating levels of vitamin D to development of asthma, asthma exacerbations and risk factors leading to development of asthma like respiratory tract infections with positive associations. A number of studies were carried out which tried to explain the possible molecular mechanisms relating deficiency of vitamin D in pathogenesis of asthma. This review summarizes the role of vitamin D in development of asthma and probable mechanisms relating vitamin D to the pathogenesis of asthma.

Risk of restless legs syndrome in low socioeconomic rheumatoid arthritis patients.

OBJECTIVES: Our aim was to determine the frequency of restless leg syndrome (RLS) in rheumatoid arthritis (RA) patients from a low socioeconomic area of Pakistan and compare results with a control group to evaluate the effect of variables on RLS patients. METHODS: A clinical observational study was carried out on 240 RA patients form low socioeconomic group. Controls (n = 210) were frequency-matched by age group to the RA patients. We evaluated the presence of RLS and collected information on characteristics believed to be correlated with RLS in the general population. Multiple logistic regression models were used to study the association between RLS and other risk factors such as age, smoking status, and obesity. RESULTS: Among all rheumatic patients seen at our rheumatology clinic, 70.8% were women. Our study shows that 20% of RA patients were suffering from RLS compared with 10% of the control group with other rheumatic diseases. Multivariate logistic regression adjusted for age, obesity, and smoking also showed that women with RA were more likely to have RLS than control patients. RLS was also significantly associated with increasing age, high body mass index, and smoking status. CONCLUSIONS: Approximately 20% of RA patients were suffering from RLS. Hence, there is need of increase awareness of RLS among rheumatologists to enhance early RLS diagnosis and appropriate management of this treatable condition.

Pericardial fluid and serum biomarkers equally predict ventricular dysfunction.

BACKGROUND: serum level of amino-terminal pro-B-type natriuretic peptide, a cardiac hormone produced by the heart, is elevated in patients with left ventricular dysfunction. The purpose of this study was to compare the abilities of serum and pericardial fluid levels of amino-terminal pro-B-type natriuretic peptide to detect the left ventricular systolic dysfunction determined by echocardiography. METHODS: 50 patients undergoing coronary artery bypass grafting were included in this study. Left ventricular systolic function was assessed using echocardiography before coronary artery bypass grafting. The samples of serum and pericardial fluid were collected during surgery, and amino-terminal pro-B-type natriuretic peptide levels were assessed by an electrochemiluminescence immunoassay. The log value of amino-terminal pro-B-type natriuretic peptide concentrations was calculated. RESULTS: the pericardial fluid levels of log amino-terminal pro-B-type natriuretic peptide were significantly elevated compared to the serum levels in patients with impaired left ventricular systolic function. Both serum and pericardial fluid levels of log amino-terminal pro-B-type natriuretic peptide correlated significantly with left ventricular ejection fraction and end-diastolic and end-systolic volume indices. Furthermore, a paired comparison of receiver operating characteristic curves showed a similar performance of amino-terminal pro-B-type natriuretic peptide levels both in serum and pericardial fluid to discriminate left ventricular systolic dysfunction. CONCLUSION: serum amino-terminal pro-B-type natriuretic peptide levels have comparable diagnostic value for left ventricular systolic dysfunction with its pericardial fluid levels in patients undergoing CABG.

Accuracy of diagnosis and relationship with quality of emergency medicine training program.

An indicator for emergency room performance is the ability to establish the correct diagnosis within the emergency room over the years. The authors chose to examine the non-congruence of Emergency Room diagnoses to that established after hospital stay for three selected years. A total of 8488 records were reviewed and all disparate diagnosis were recorded and categorized. Retrospective chart reviews were done from July 2008 to February 2009 at the Aga Khan University Hospital, Karachi. A substantial reduction in the percentage of disparate diagnoses was seen over the years from 41% in the initial year to 14% in the last year evaluated. It was concluded that over the years there has been an improvement in the reliability of Emergency Room diagnoses at the Aga Khan University Hospital, Karachi.

Leflunomide or methotrexate? Comparison of clinical efficacy and safety in low socio-economic rheumatoid arthritis patients.

In order to compare the efficacy and toxicity of methotrexate and leflunomide for the treatment of rheumatoid arthritis, a double-blind randomized clinical trial was carried out at the Department of Medicine, Jinnah Medical College Hospital, Korangi, Karachi. The sample size was 240 patients and the duration of the study was 1 year. The patients enrolled were randomly divided into two groups (methotrexate and leflunomide). RA activity was clinically assessed by noting changes in the four primary (tender joint count, swollen joint count, physician and patient global assessment score) and three secondary (morning stiffness, pain intensity, HAQ) clinical efficacy end-points. Data were expressed as the mean ± SD. A P value of <0.05, calculated by paired t test, was considered significant. A total of 368 subjects were enrolled in this study. Of these, 128 subjects were withdrawn during the screening phase. Of the 240 subjects who were randomized and treated, 129 received leflunomide and 111 received methotrexate. The difference between the baseline and 12 month end-point measurements of all primary clinical efficacy end-points was significantly greater in methotrexate-treated than in leflunomide-treated subjects. Both leflunomide and methotrexate resulted in significant improvements in all secondary clinical efficacy end-points after 1 year of treatment. In both treatment groups, the most common reason for withdrawal during the treatment was adverse events. The results of this study indicate that both leflunomide and methotrexate are effective drugs for the long-term treatment of RA. It was concluded that methotrexate, which is a much cheaper drug than leflunomide, is the drug of choice, especially for patients who belong to low socioeconomic groups.

Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes.

Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are a variable and rapidly evolving family of MHC Class I receptors. Studied here is KIR3DL1/S1, which encodes receptors for highly polymorphic human HLA-A and -B and comprises three ancient allelic lineages that have been preserved by balancing selection throughout human evolution. While the 3DS1 lineage of activating receptors has been conserved, the two 3DL1 lineages of inhibitory receptors were diversified through inter-lineage recombination with each other and with 3DS1. Prominent targets for recombination were D0-domain polymorphisms, which modulate enhancer function, and dimorphism at position 283 in the D2 domain, which influences inhibitory function. In African populations, unequal crossing over between the 3DL1 and 3DL2 genes produced a deleted KIR haplotype in which the telomeric "half" was reduced to a single fusion gene with functional properties distinct from its 3DL1 and 3DL2 parents. Conversely, in Eurasian populations, duplication of the KIR3DL1/S1 locus by unequal crossing over has enabled individuals to carry and express alleles of all three KIR3DL1/S1 lineages. These results demonstrate how meiotic recombination combines with an ancient, preserved diversity to create new KIR phenotypes upon which natural selection acts. A consequence of such recombination is to blur the distinction between alleles and loci in the rapidly evolving human KIR gene family.

Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans.

Interactions of killer cell immunoglobulin-like receptors (KIRs) with major histocompatibility complex (MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of protein">HLA-A and HLA-B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years. Variation was selected at D1 and D2 domain residues that contact HLA class I and at two sites on D0, the domain that enhances the binding of KIR3D to HLA class I. HLA-B variants that gained Bw4 through interallelic microconversion are also products of selection. A worldwide comparison uncovers unusual KIR3DL1/S1 evolution in modern sub-Saharan Africans. Balancing selection is weak and confined to D0, KIR3DS1 is rare and KIR3DL1 allotypes with similar binding sites predominate. Natural killer cells express the dominant KIR3DL1 at a high frequency and with high surface density, providing strong responses to cells perturbed in Bw4 expression.