Biomedical subjects

M A Little

Publications and source records attributed to M A Little.

At least 19 recordsLinked to original sources

PubMed2006

Severity of primary MPGN, rather than MPGN type, determines renal survival and post-transplantation recurrence risk.

Previous studies suggested that membranoproliferative glomerulonephritis (MPGN) type II has a worse renal survival and an unacceptable risk of recurrence post transplantation. We hypothesised that other factors may determine this risk. We analysed all cases (n=70) of MPGN diagnosed by renal biopsy in Ireland from 1972 to 1995. We used Cox regression analysis to determine factors that were independently predictive of renal failure. MPGN II had more crescent formation and mesangial proliferation (P<0.05). Mean follow-up duration was 13.8 years, during which time 41 (58.6%) developed end-stage renal failure (ESRF). The median time to ESRF was 8.3 years (95% confidence interval 5.7-10.9) and 5-, 10-, and 20-year probabilities of ESRF were 32, 54, and 70%, respectively. Multivariate analysis revealed that severity of interstitial fibrosis (P<0.05), crescent formation (P<0. 01) and mesangial proliferation (P<0.05) were independently associated with ESRF. Decade of diagnosis, age, MPGN type, and creatinine or complement level at baseline did not predict renal survival in this model. In 21 (49%) of the 43 renal transplants, MPGN recurred. Younger age at initial diagnosis (P<0.01) and the presence of crescents on the original biopsy (P<0.005) were independently associated with recurrence on multivariate analysis. MPGN type was not associated with recurrence in this model. Contrary to previous reports, after controlling for crescent formation, MPGN II was not associated with more ESRF or recurrence in the allograft. It is therefore the more aggressive glomerular changes associated with MPGN II, rather than the disease type per se, that determine outcome.

Adolescent↗

PubMed2006

Testing the assumptions of linear prediction analysis in normal vowels.

In this paper we develop an improved surrogate data test to show experimental evidence, for all the simple vowels of U.S. English, for both male and female speakers, that Gaussian linear prediction analysis, a ubiquitous technique in current speech technologies, cannot be used to extract all the dynamical structure of real speech time series. The test provides robust evidence undermining the validity of these linear techniques, supporting the assumptions of either dynamical nonlinearity and/or non-Gaussianity common to more recent, complex, efforts at dynamical modeling speech time series. However, an additional finding is that the classical assumptions cannot be ruled out entirely, and plausible evidence is given to explain the success of the linear Gaussian theory as a weak approximation to the true, nonlinear/non-Gaussian dynamics. This supports the use of appropriate hybrid linear/nonlinear/non-Gaussian modeling. With a calibrated calculation of statistic and particular choice of experimental protocol, some of the known systematic problems of the method of surrogate data testing are circumvented to obtain results to support the conclusions to a high level of significance.

Female↗

PubMed2006

Current and future therapy of small vessel vasculitis of the kidney.

Renal involvement, characterised histologically by crescentic glomerulonephritis, is the most potent clinical determinant of long-term outcome in ANCA-associated systemic vasculitis (AASV). The presence of autoantibodies against neutrophil granule constituents may be an important pathogenic factor. The duration and intensity of treatment of renal vasculitis with standard induction therapies (prednisolone and cyclophosphamide) have been clarified by the completion of a number of prospective clinical trials. Based on these, most patients with renal vasculitis should receive 3 months of pulsed intravenous or oral cyclophosphamide plus tailing doses of prednisolone, with switching to azathioprine plus prednisolone thereafter for a minimum of 2 years. Added to this therapeutic backbone are methotrexate, plasma exchange and mycophenolate mofetil, use of which has been addressed by further prospective trials, most of which have been conducted by the European Vasculitis Study Group. Additional therapies, such as intravenous immunoglobulin and antithymocyte globulin may be used in cases of resistant vasculitis and when cyclophosphamide is poorly tolerated. Newer biologic agents are now emerging and are being subjected to rigorous testing. Of these, monoclonal antibodies directed against TNFa (a central cytokine in AASV pathogenesis) and CD20 (a specific B-cell marker) are proving most promising. This review will put these various therapeutic approaches into the context of renal vasculitis, with emphasis on a practical approach to management.

Decision Trees↗

PubMed2005

Intravital microscopy in the study of ANCA-associated systemic vasculitis.

In addition to being useful clinical markers of systemic vasculitis, anti-neutrophil cytoplasm antibodies (ANCA) may play a role in the initiation of vasculitic injury. These autoantibodies can induce neutrophil degranulation, dysregulated neutrophil apoptosis and neutrophil adhesion to endothelium in static cellular systems. This mini-review will place these sentinel findings in the context of more recent studies using the parallel plate flow chamber and novel animal models of ANCA-associated vasculitis (AASV). Rodent models lend themselves well to investigation of leukocyte endothelial interaction using intravital microscopy. In this way, one can study ANCA-induced leukocyte adhesion/transmigration, and microvascular injury in real time. These studies may then be extended to look at the impact of novel therapeutic agents on these processes.

Animals↗

PubMed2004

Short-chain acyl-CoA dehydrogenase deficiency associated with early onset severe axonal neuropathy.

Two unusual cases of axonal neuropathy associated with short-chain acyl-CoA dehydrogenase (SCAD) deficiency are described. These two unrelated infants presented with profound generalised weakness, particularly affecting the upper limbs. Clinical examination revealed generalised peripheral hypotonia and weakness, with absent deep tendon reflexes. An axonal polyneuropathy was confirmed on electromyogram (EMG) and nerve conduction studies (NCS) and, following an extensive metabolic screen, an acylcarnitine and organic acid profile consistent with a short-chain fatty acid beta-oxidation defect was found. In both cases, SCAD deficiency was confirmed by enzyme analysis. Genetic analysis showed the presence of common gene variations in the SCAD gene. SCAD deficiency is a rare disorder with a wide clinical phenotype. SCAD deficiency associated with axonal neuropathy has not previously been reported. As highlighted in these cases, it may be necessary to include axonal neuropathy as a presenting feature of SCAD.

Age of Onset↗

PubMed2004

Polymyalgia rheumatica preceding small-vessel vasculitis: changed spots or misdiagnosis?

BACKGROUND: Systemic small-vessel vasculitis (SVV) is increasing in incidence and age of diagnosis. Presenting features may mimic those of polymyalgia rheumatica (PMR), a common disease of the elderly. AIM: To test the hypotheses that SVV is frequently misdiagnosed as PMR in elderly patients, that this results in a delay in diagnosis and appropriate treatment, and that the natural history and clinical features are different. DESIGN: Retrospective case-control study. METHODS: Cases of glomerulonephritis due to SVV at a single centre over a 12-year period were analysed, comparing those treated previously for PMR (PMR(+)) to the remainder of the cohort (PMR(-)). RESULTS: Of 86 patients with complete follow-up, 13% had been treated previously for PMR. PMR(+) patients had a longer duration of symptoms prior to SVV diagnosis (396 vs. 107 days, p = 0.001) and were less likely to be dialysis-dependent at diagnosis (36% vs. 68%, p < 0.05). Despite the delay in diagnosis, there was a trend towards lower serum creatinine (392 vs. 591 micro M), lower relapse rate (0.04 versus 0.15 episodes/patient-year) and lower incidence of death/end-stage renal failure (27% vs. 53%) in the PMR(+) group. DISCUSSION: SVV is frequently misdiagnosed as PMR, especially in those patients with indolent disease, although this did not appear to adversely affect outcome. We recommend that all patients suspected of suffering from PMR undergo careful urinalysis to look for haematuria or proteinuria, and that a low threshold for ANCA testing is maintained.

Aged↗

PubMed2002

A randomised study of prophylactic G-CSF following MRC UKALL XI intensification regimen in childhood ALL and T-NHL.

BACKGROUND: Despite the current widespread use of prophylactic G-CSF in children with solid tumours and leukaemia, its effectiveness has not been clearly demonstrated. This randomised study evaluates the role of G-CSF given after a 5-day intensification block in children with acute lymphoblastic leukaemia (ALL). PROCEDURE: Forty-six children with ALL or T-Cell non-Hodgkins lymphoma (NHL) treated on MRC ALL 97, UKALL XI or UKCCSG 9504 NHL protocols were randomised to receive granulocyte colony-stimulating factor following either the first or the second block of intensive chemotherapy in a cross-over study to determine if the prophylactic administration of G-CSF could reduce the rate of readmission to hospital for management of febrile neutropenia. RESULTS: There was a statistically significant difference in the rate of hospital admission in the group receiving prophylaxis, with 34 of 46 being admitted, compared to 42 of 46 patients in the control arm (74 vs. 91%; P=0.0386). There were no differences found in duration of hospital admission, haematological toxicity, neutrophil recovery or duration of supportive care between the two groups. There was no demonstrable cost benefit derived from the prophylactic administration of G-CSF. CONCLUSIONS: This study shows that the prophylactic administration of G-CSF following intensification chemotherapy for childhood ALL and T-NHL produces a significant reduction in the rate of readmission to hospital for the management of febrile neutropenia.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin.

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin.

Adolescent↗

PubMed2001

Severity of renal vascular disease predicts mortality in patients undergoing coronary angiography.

BACKGROUND: Renal artery stenosis (RAS) is a relatively uncommon but potentially reversible cause of renal failure. In a previous report, we demonstrated that the presence of RAS is independently associated with mortality in a group of patients undergoing coronary angiography. Our current study expands on this cohort, investigating the effect of the severity of RAS on all-cause mortality. METHODS: A total of 3987 patients underwent abdominal aortography immediately following coronary angiography. For the purpose of survival analysis, significant RAS was defined as > or =75% narrowing in the luminal diameter. RESULTS: Significant RAS was present in 4.8% of patients studied and was bilateral in 0.8%. Factors associated with the presence of RAS included female gender, older age, hypertension, congestive heart failure, elevated serum creatinine, and congestive heart failure. The four-year unadjusted survivals for patients with and without significant RAS were 57 and 89%, respectively (P < 0.001). Using the Cox proportional hazards model, the factors independently associated with decreased survival were the presence of RAS, increased age, the severity of coronary artery disease, the presence of comorbid disease, reduced ejection fraction, symptoms of congestive cardiac failure, and the mode of treatment of coronary artery disease. In the multivariate model, the presence of RAS conferred a hazard ratio of 2.01 (95% CI, 1.51 to 2.67, P < 0.001). We demonstrated an incremental effect on mortality according to the severity of RAS at baseline. Four-year adjusted survival for patients with 50%, 75%, and > or =95% stenosis was 70%, 68%, and 48%, respectively. In addition, bilateral disease was associated with four-year survival of 47% as compared with 59% for patients with unilateral disease (P < 0.001). The impact of RAS on survival remained robust regardless of the manner of treatment of coronary artery disease [that is, medical, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass graft (CABG)]. CONCLUSIONS: In this patient population, the presence of RAS is a strong independent predictor of mortality. Increasing severity of RAS has an incremental effect on survival probability.

Aged↗

PubMed2001

A prospective study of complications associated with cuffed, tunnelled haemodialysis catheters.

BACKGROUND: Despite the US Dialysis Outcome Quality Initiative )DOQI( guidelines, for various reasons, increasing numbers of end-stage renal disease patients are becoming dependent on cuffed haemodialysis catheters (HCs) for chronic haemodialysis access. Their use is complicated by frequent failure due to thrombosis and catheter-related sepsis. In our unit, all HCs are put in place by the radiology department. METHODS: In a prospective study we looked at the outcome of all HCs over a three-year period, during which time 573 consecutive HCs were placed in 336 patients. Each line was followed individually until it was removed or until the end of the study. RESULTS: In a survival analysis of those HCs removed following HC failure, HC half-life was 312 days and one-year HC survival was 47.5%. The most frequent indications for HC removal were non-function (36.6%), clinical suspicion of line sepsis (16.4%) and patient death (14.4%). Using a Cox proportional hazards model, catheter number in a given patient and the presence of diabetes mellitus were found to be independent predictors of HC failure. The total incidence of HC-related sepsis was 1.3 episodes/1000 catheter days. The probability of developing bacteraemic HC-related sepsis was 27.5% at one year. CONCLUSIONS: Less than half of the HCs were removed electively because of availability of a more permanent mode of renal replacement, thereby illustrating the level of dependence that has developed on them as permanent access. Consequently, their limitations (infection and malfunction) are placing an ever increasing burden on the healthcare services.

Catheters, Indwelling↗

PubMed2000

Hemolytic-uremic syndrome in association with both cyclosporine and tacrolimus.

Hemolytic-uremic syndrome (HUS) is a well-recognized complication of cyclosporine (CyA) therapy. Transplant recipients with this complication are frequently switched to tacrolimus, although this drug has also been implicated. We report a case of a renal transplant recipient who developed severe graft dysfunction due to biopsy-proven HUS after receiving CyA. Renal function and hemolytic parameters improved with discontinuation of the drug, but they deteriorated again after commencement of tacrolimus 15 days later. A second transplant biopsy demonstrated fresh lesions diagnostic of HUS. Hemolytic parameters resolved with discontinuation of tacrolimus. This is the first report of metachronous HUS being caused in a renal transplant by both CyA and tacrolimus. We therefore believe that caution should be exercised when using tacrolimus as rescue therapy in patients with CyA-induced HUS.

Biopsy↗

PubMed2000

Access recirculation in temporary hemodialysis catheters as measured by the saline dilution technique.

Ultrasound dilution technology is emerging as the standard for measuring access recirculation and blood flow in hemodialysis patients. In temporary dialysis catheters, studies using the traditional two-needle urea method have suggested that short femoral catheters are associated with an unacceptably high degree of recirculation. This problem has never been assessed using ultrasound dilution technology. We performed a prospective observational study of consecutive patients undergoing dialysis through a temporary catheter. Measurements were made on 49 catheters; 10 catheters were excluded because poor flow necessitated reversal of the dialysis ports. Thirty-nine catheters in 33 patients were included in this analysis, of which 26 catheters were located in the femoral vein, and 13 catheters, in the internal jugular vein. Dialyzer blood flow was adjusted to give an ultrasonic flow rate of 250 mL/min (actual mean blood flow, 234.3 mL/min; 95% confidence interval [CI], 228 to 241). Overall mean recirculation rate was 8.9% (95% CI, 4.8 to 13.0). Multivariate analysis showed catheter location and length to be independent predictors of recirculation. Blood flow (within the range tested), duration into dialysis, time since catheter insertion, cardiac rhythm, and catheter type had no significant effect on recirculation rates. Recirculation in femoral catheters (13.1%) was significantly greater than that in internal jugular catheters (0.4%; P: < 0.001). Femoral catheters shorter than 20 cm had significantly greater recirculation (26.3%) than those longer than 20 cm (8.3%; P: = 0.007). We conclude that temporary femoral catheters shorter than 20 cm are associated with increased recirculation rates. In addition, when dialysis dose delivery is a priority, locating the temporary catheter in the internal jugular vein is an advantage.

Adult↗

PubMed2000

Mesangioproliferative glomerulonephritis with IgM deposition: clinical characteristics and outcome.

The significance of IgM on immunofluorescence in renal biopsy specimens remains unclear. This retrospective case study was conducted to define the clinical features, response to therapy and outcome of patients with Mesangioproliferative Glomerulonephritis (MGN) with diffuse IgM deposition. Of 1919 native renal biopsies performed over a ten-year period, 139 (7.2%) had light microscopic features of MGN and manifested IgM as the dominant immunoglobulin. When exclusion criteria (more than a trace of IgA or IgG, segmental IgM, evidence of SLE, vasculitis, FSGS or Alport's syndrome and pregnant patients) were applied, 60 patients (3.1%) remained. Follow-up data were available for 54 cases with a mean age of 26.5 years (range 1.7-63). Mean follow-up period was 7.4 years (range 4.7-22.2). Forty-one per cent presented with nephrotic syndrome (NS), 26% with asymptomatic proteinuria (>250mg/24hr), 18% with macroscopic hematuria and 15% with isolated microscopic hematuria. Twenty-one percent of patients were hypertensive at presentation. Creatinine was initially <120 (mol/L in all but one patient. Only four patients (7.4%), all nephrotic, suffered a decline in renal function despite treatment; all 4 developed ESRF after a mean of 5.6 years (range 2-8.3). Two of these were subsequently re-biopsied and found to have FSGS. No patients with isolated microscopic / macroscopic hematuria or asymptomatic proteinuria suffered a decline in renal function. Protein excretion rate fell into the normal range in 63% of those receiving steroids, with 82% becoming steroid dependent. Of those treated with cyclosporine (48%) or cyclophosphamide (52%) only 9.5% and 14.5% respectively remained in prolonged remission after discontinuing treatment. It is concluded that MGN with IgM deposition carries a very favorable prognosis except in patients with NS who develop FSGS. However there is a high incidence of steroid dependence and resistance in the proteinuric group.

Adolescent↗

PubMed2000

The diagnostic yield of intravenous urography.

BACKGROUND: Intravenous urography (IVU) is considered an integral imaging component of the nephro-urological work-up in a wide array of clinical settings. At our institution there is an open-access policy with regard to requesting IVU studies. METHODS: In a prospective, blinded observational study we undertook to assess the diagnostic yield of IVU with respect to the source of referral (i.e. Urology, Nephrology, GP, A & E, other speciality) and the presenting features, such as renal colic, haematuria, bladder outflow obstruction, recurrent urinary tract infection (UTI) etc. Two hundred consecutive patients were evaluated. RESULTS: Overall, 23% of tests were positive. There was a highly significant difference in diagnostic yield between the groups (P<0.001 for both referral source and test indication). A positive result was most likely after referral by a kidney specialist (37.1%) and when the test indication was renal colic (42%) or haematuria (32%). The yield was <15% in all other circumstances, with 94.9% and 92.1% of GP- and other hospital speciality-initiated IVUs being negative. When investigating recurrent UTI, 91.7% of tests were negative and 86.2% were negative when the indication was bladder outflow obstruction. CONCLUSIONS: It is suggested that an open access policy for IVU is not justified, especially when cost and the risk associated with contrast media and radiation exposure are taken into account. Our study supports the abandonment of routine IVU in the investigation of UTI and bladder outflow obstruction.

Adolescent↗

PubMed2000

Human adaptability research into the beginning of the third millennium.

Human adaptability, as a field of inquiry within human biology, became defined during the research activities of the International Biological Program (IBP) (1964-1974). During this period, research was focused on ecological, physiological, and genetic studies of human populations within the theoretical frameworks of adaptation and evolution. Other defining characteristics of the IBP human adaptability research were standardization of methods, multidisciplinary projects, international cooperation, and a concern with human health issues. Some observers suggest that this research contributed to the ongoing transformation of physical anthropology and related fields from a largely descriptive to an analytical science. During the 25 years between the end of the IBP and the present, a number of research trends have continued: Several new multidisciplinary projects were initiated and completed; a subfield of demography within human biology has matured; nutrition, infant and child growth, and health studies have proliferated; and molecular genetics and DNA analysis have superseded the earlier population genetics. International programs today are geared toward more practical and applied studies with less emphasis on basic science. Continuation of human adaptability research into the 21st century is likely to make contributions in 3 broad areas: population, environment, and health. Productive research is likely to contribute to these 3 areas in the following categories: reproduction, psychosocial stress, life span approaches to health, effects of losses in biodiversity on health, a human biology of poverty, emerging infectious diseases, epidemiology of modernization, evolutionary medicine, and aging. The success of much of this research in its contribution to knowledge will come from the integrated perspectives of a biobehavioral framework of inquiry.

Adaptation, Physiological↗

PubMed2000

A novel presentation of cryptococcal infection in a renal allograft recipient.

The population of immunosuppressed patients is growing rapidly because of the HIV epidemic and the rapid expansion in transplant medicine. These patients may present to a variety of clinical specialties with seemingly innocuous infections. We present here the first Irish case of primary cryptococcal cellulitis. The patient was a 62-year old renal transplant recipient and was immunosuppressed with Cyclosporine, Azathioprine and Prednisolone. He presented with an apparent bacterial cellulitis on the dorsum of the hand that had failed to respond to a 3-week course of oral antibiotics. There was no clinical evidence of systemic infection. There was tissue necrosis present and the area was debrided surgically. Histological examination of debrided tissue revealed necrotic granulomata and budding yeast-like organisms. Cryptococcus neoformans was cultured from this specimen. The patient was treated with oral fluconazole 400 mg daily for 6 weeks with complete healing of the infected area and no evidence of recurrence after 12 months of follow up. This case emphasises the need for a high index of suspicion for atypical infection in the immunocompromised patient.

Antifungal Agents↗

PubMed1999

Natural experimental models: the global search for biomedical paradigms among traditional, modernizing, and modern populations.

During the past four decades, biomedical scientists have slowly begun to recognize the unique opportunities for studying biomedical processes, disease etiology, and mechanisms of pathogenesis in populations with unusual genetic structures, physiological characteristics, focal endemic disease, or special circumstances. Such populations greatly extend our research capabilities and provide a natural laboratory for studying relationships among biobehavioral, genetic, and ecological processes that are involved in the development of disease. The models presented illustrate three different types of natural experiments: those occurring in traditionally living, modernizing, and modern populations. The examples are drawn from current research that involves population mechanisms of adaptation among East African Turkana pastoralists; a search for etiology and mechanisms of pathogenesis of an emerging disease among the Yakut people of Siberia; and psychosocial stress, hypertension, and cardiovascular disease in women working outside the home in New York City and among subpopulations in Hawaii. The models in general, and the examples in specific, represent natural laboratories in which relatively small intrapopulation differences and large interpopulation differences can be used to evaluate health and disease outcomes.

Africa, Eastern↗

PubMed1996

Evaluation of reproductive function in Turkana women with enzyme immunoassays of urinary hormones in the field.

The frequently reported observation that nomadic populations have lower fertility than their settled counterparts is often attributed to what are perceived as harsh, stressful conditions under which the nomads live. But the consequences of the hypothesized stresses for the reproductive biology or demography of these populations have been documented only a little. Traditionally, the Turkana of northwest Kenya are nomadic herders, but increasing numbers have settled on agricultural development schemes. We used an array of hormonal assays along with anthropometric indexes of nutritional status and interviews covering reproductive history, recent menstruation, diet, and health to compare reproductive function in nomadic and settled Turkana women. First morning urine samples were collected for three consecutive days during a series of surveys. Human choriogonadotropin (hCG; a marker for pregnancy), luteinizing hormone (LH; an indicator of ovulation), and pregnanediol glucuronide (PdG; an indicator of postovulatory luteal function) were assessed in the field with commercially available dipstick enzyme immunoassays. These assays along with the interview data allowed us to determine the reproductive status (e.g., pregnant or cycling, and if cycling, which phase of the ovarian cycle) of 166 nomadic and 194 settled Turkana women. The cross-sectional classifications allowed inferences of conception rates and normality of ovarian function. Follow-up surveys provided rates of pregnancy loss. Compared with the settled women, the nomadic women exhibited lower pregnancy rates and cycling nomadic women were less likely to show evidence of ovulation or luteal function. These results suggest that reproductive function of the nomadic women is diminished relative to the settled women. However, the settled women experienced a much higher rate of pregnancy loss, which may mean that their effective fecundability is in fact lower than that of the nomadic women. This study is the first to apply such a wide range of hormonal assays in the field. It demonstrates that field-based assays are feasible and robust and can play an important role in epidemiological and biodemographic studies, even in remote locations under conditions that would ordinarily be considered incompatible with on-site laboratory analysis.

Adolescent↗