Leprosy in the early medieval Lauchheim community

Leprosy was a well-recognized and dreaded disease in medieval Europe (5th-15th century AD). It is reported to have reached Germany with the Roman invasion. A much larger fraction than previously assumed appears to have been affected by leprosy in the medieval period. This article estimates the frequency (i.e., the prevalence at death) of leprosy among adult people buried in the Lauchheim early medieval cemetery. Seven different dichotomous osteological lesions indicative of leprosy are analyzed, and it is possible to score at least one of these conditions on 110 adult skeletons (aged 15 or more). The scores were transformed to a statistic--lambda (lambda)--indicating the likelihood that the person to whom the skeleton belonged suffered from leprosy. The analyses indicate that 16% (95% confidence interval: 9-23%) of adult people in Lauchheim died with osteological signs of leprosy. Leprosy was significantly more prevalent among men than women. The lambda statistic indicates that people who died with signs of leprosy did not differ in the distribution of age at death from those who did not have such signs. Some of the leprosy-related lesions had a statistically significant nonrandom dispersal on the cemetery; but there is no clear pattern to this and the significant results could be easily attributed to a type-1 error in the statistical analysis.     

Outside St. Jørgen: leprosy in the medieval Danish city of Odense

Leprosy was a common and dreaded disease in the Danish Middle Ages (AD 1050-1536). Starting in the second half of the 13th century, leprosaria were established in many Danish towns and cities. In the city of Odense (on the island of Funen, Denmark), the cemetery of the leprosarium was totally excavated, and four nonleprosarium medieval and early modern cemeteries have been partly excavated. This paper explores the frequency of leprosy in the nonleprosarium cemeteries in Odense, and looks for evidence of selective exclusion from the ordinary population. The analyses are based on 733 skeletons from four cemeteries in Odense: the Gray Friars monastery, St. Albani parish church, St. Knuds cathedral, and Black Friars monastery. Seven lesions are scored and, based on known epidemiological properties (i.e., specificity and sensitivity) of these lesions, scores were transformed to statistics characterizing an individual's risk of having suffered from leprosy. This statistical approach remains of primary theoretical value, pending confirmation by independent research groups at other sites. Prevalence of the skeletal manifestation of leprosy at death varied between 0-17% among the different cemeteries in Odense. The highest prevalence was seen in cemeteries with many burials before AD 1400. It is estimated that before AD 1400, between 14-17% of those buried in the nonleprosarium cemeteries suffered from leprosy. In all nonleprosarium cemeteries, there was evidence for selective exclusion of people with facial leprosy lesions. For a short period just up to AD 1300, the cemetery of the Odense leprosarium had, on average, more than 20 yearly burials. The establishment of the leprosarium was followed within a relatively short period by a dramatic decline in the number of sufferers of leprosy in the nonleprosarium cemeteries. The number of yearly burials in the leprosarium cemetery also declined rapidly during the 14th century. The present analyses do not permit conclusions about the reasons for this decline in leprosy prevalence.     

Fractures in late medieval skeletal populations from Serbia

Bone fractures were analyzed from skeletal remains of 861 adult individuals from six cemeteries dating to the Late Medieval period in Serbia. Results of the study were compared to other cemetery populations (635 individual skeletons) of the same date and region in an attempt to understand fracture patterns. The association of types of fractures and their prevalence with sex, age at death, cemetery site, and information deriving from historical sources are discussed. Results showed that the long bone fracture frequency was 0.7%, and the majority of the fractures were the result of direct force. This rate is similar to some studies of contemporary British skeletal samples. However, it is much lower than for some other Old World sites. Cranial vault fractures had a rate of 6.7%, and of the facial skeleton, 1.3%; the frontal bone was the most affected of bones of the cranial vault. Injuries were more common on the upper extremities (0.8%) compared to the lower (0.6%). However, the fibula was the most fractured bone (2.8%), followed by the ulna (2.4%). This pattern is similar to three of six Late Medieval urban sites in Britain. These findings suggest that this rural community was exposed to a low risk of trauma, probably related mostly to accidents sustained during farming, and rarely to interpersonal violence.     

Concordance of cranial and dental morphological traits and evidence for endogamy in ancient Egypt

A biological affinities study based on frequencies of cranial nonmetric traits in skeletal samples from three cemeteries at predynastic Naqada, Egypt, confirms the results of a recent nonmetric dental morphological analysis. Both cranial and dental traits analyses indicate that the individuals buried in a cemetery characterized archaeologically as high status are significantly different from individuals buried in two other, apparently nonelite cemeteries and that the nonelite samples are not significantly different from each other. A comparison with neighbouring Nile Valley skeletal samples suggests that the high status cemetery represents an endogamous ruling or elite segment of the local population at Naqada, which is more closely related to populations in northern Nubia than to neighbouring populations in southern Egypt. © 1996 Wiley-Liss, Inc.     

Testing conditional independence in diagnostic palaeoepidemiology

Leprosy was a well-known and dreaded disease in the Middle Ages. A substantial fraction of the adult population carried leprosy-related lesions. Previous research analyzed the occurrence and implications of seven such lesions in samples of medieval skeletons. These analyses were carried out under the assumption of conditional independence among lesion scores. The present paper examines this assumption by developing a test based on the odds ratios and applying the test to three rural medieval samples from Europe: Tirup from the 12th-14th century AD in Jutland, Denmark; Refshale from the 12th-14th century AD on the island of Lolland, Denmark; and Lauchheim from AD 460-680 in southern Germany. Signs of nonzero prevalence of leprosy at death were found in all three samples: Tirup, 25.5% (95% CI, 17.2-34.6%); Refshale, 39.1% (95% CI, 25.5-54.7%); and Lauchheim, 16.2% (95% CI, 10.0-22.9%). It is shown that when leprosy is the prime factor creating variation in the lesion scores in and between samples, the assumption of conditional independence cannot be rejected.     

A case of canine hypodontia in an early Croatian cemetery Strance-Gorica

In the old Croatian cemetery Strance-Gorica in the Vinodol region, dating from the 9th to 11th century, osteological parts of the upper and the lower jaws with teeth were found, besides some other archeological finds. Data processing in dentistry regarding a possible presence of hypodontia was carried out on archeological finds (skeletal remains) on 27 persons available for the research. Only one case of canine hypodontia was found and described. In the remaining 26 persons no case of hypodontia was found on the relicts of the upper and lower jaws nor in other teeth groups. The frequency of hypodontia in the old Croatian cemetery Strance-Gorica was 3.7, which corresponds to the frequency of this anomaly in the 20th century population of Croatia.     

Accuracy of mucocutaneous leishmaniasis diagnosis using polymerase chain reaction: systematic literature review and meta-analysis

The diagnosis of mucocutaneous leishmaniasis (MCL) is hampered by the absence of a gold standard. An accurate diagnosis is essential because of the high toxicity of the medications for the disease. This study aimed to assess the ability of polymerase chain reaction (PCR) to identify MCL and to compare these results with clinical research recently published by the authors. A systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement was performed using comprehensive search criteria and communication with the authors. A meta-analysis considering the estimates of the univariate and bivariate models was performed. Specificity near 100% was common among the papers. The primary reason for accuracy differences was sensitivity. The meta-analysis, which was only possible for PCR samples of lesion fragments, revealed a sensitivity of 71% [95% confidence interval (CI) = 0.59; 0.81] and a specificity of 93% (95% CI = 0.83; 0.98) in the bivariate model. The search for measures that could increase the sensitivity of PCR should be encouraged. The quality of the collected material and the optimisation of the amplification of genetic material should be prioritised.     

Diagnostic Accuracy of Copeptin in the Differential Diagnosis of Patients With Diabetes Insipidus: A Systematic Review and Meta-analysis

ObjectiveAccurate diagnosis of diabetes insipidus (DI) is of significant importance for correct management. We aimed to evaluate the diagnostic accuracy of copeptin level measurements in the differential diagnosis between DI and primary polydipsia (PP).MethodsA literature search of electronic databases from January 1, 2005, to July 13, 2022, was performed. Primary studies that evaluated the diagnostic accuracy of copeptin concentration in patients with DI and PP were considered eligible. Two reviewers independently screened relevant articles and extracted data. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the quality of the included studies. The hierarchical summary receiver operating characteristic model and bivariate method were used.ResultsSeven studies including 422 patients with polydipsia-polyuria syndrome were included; of the 422 patients, 189 (44.79%) presented with arginine vasopressin deficiency (AVP-D, cranial DI) and 212 (50.24%) with PP. The summary estimates of the diagnostic performance of stimulated copeptin to differentiate between PP and AVP-D were 0.93 (95% CI, 0.89-0.97) for sensitivity and 0.96 (95% CI, 0.88-1.00) for specificity. Baseline copeptin level showed high performance in identifying AVP resistance (nephrogenic DI), with a pooled sensitivity of 1.00 (95% CI, 0.82-1.00) and specificity of 1.00 (95% CI, 0.98-1.00); however, it showed little value in the differentiation between PP and AVP-D.ConclusionCopeptin level measurement is a useful tool for the differential diagnosis of patients with DI and PP. Stimulation before copeptin measurement is necessary in the diagnosis of AVP-D.     

Bilateral asymmetry in skeletal growth and maturation as an indicator of environmental stress.

This study examined the efficacy of bilateral asymmetry in epiphyseal union as an indicator of environmental stress affecting the skeleton. We compared the extent of asymmetry in the postcranial skeleton between two cemetery samples excavated from Medieval Kulubnarti, Sudanese Nubia. Past studies have strongly suggested that these ancient Nubians experienced environmental stress-the early Christian period (550-750 AD) population to a greater extent than the late Christian period (750-1450 AD) population. We hypothesized that if bilateral asymmetry is a reflection of stress, then it should be present or greater in the more stressed population, the early Christian period population, while absent or found to a lesser extent in the less stressed population, the late Christian period population. We computed two mean values, representative of right-side and left-side epiphyseal union, for each individual in both cemetery samples, and tested for significant differences. Bilateral asymmetry was significant in the combined cemetery sample of 90 individuals (P < 0.019). When cemetery samples were tested separately, bilateral asymmetry was significant for the early Christian period sample (P < 0.001), but not for the late Christian period sample. There were no differences attributable to sex. Finally, we discuss why we conclude that environmental stress was favored over a biomechanic explanation as the cause for asymmetry. To the extent that our results support previous findings that early Christian period individuals were more affected by environmental stress than late Christian period individuals, it is reasonable to consider bilateral asymmetry in skeletal growth and maturation a good indicator of environmental stress.     

Comparison of child morbidity in two contrasting medieval cemeteries from Denmark

This study compares associations between demographic profiles, long bone lengths, bone mineral content, and frequencies of stress indicators in the preadult populations of two medieval skeletal assemblages from Denmark. One is from a leprosarium, and thus probably represents a disadvantaged group (Naestved). The other comes from a normal, and in comparison rather privileged, medieval community (AEbelholt). Previous studies of the adult population indicated differences between the two skeletal collections with regard to mortality, dental size, and metabolic and specific infectious disease. The two samples were analyzed against the view known as the "osteological paradox" (Wood et al. [1992] Curr. Anthropol. 33:343-370), according to which skeletons displaying pathological modification are likely to represent the healthier individuals of a population, whereas those without lesions would have died without acquiring modifications as a result of a depressed immune response. Results reveal that older age groups among the preadults from Naestved are shorter and have less bone mineral content than their peers from AEbelholt. On average, the Naestved children have a higher prevalence of stress indicators, and in some cases display skeletal signs of leprosy. This is likely a result of the combination of compromised health and social disadvantage, thus supporting a more traditional interpretation. The study provides insights into the health of children from two different biocultural settings of medieval Danish society and illustrates the importance of comparing samples of single age groups.     

Diagnostic value of nucleic acid amplification tests on bronchoalveolar lavage fluid for smear-negative pulmonary tuberculosis: a meta-analysis

The diagnosis of smear-negative pulmonary tuberculosis (SNPT) remains a clinical challenge. Many studies suggest that nucleic acid amplification tests (NAATs) on bronchoalveolar lavage fluid (BALF) plays a role in diagnosing SNPT, but with considerable varying results. The current study aimed to summarize the overall diagnostic accuracy of NAATs assay on BALF for SNPT. A systematic literature search was performed and data were retrieved. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were calculated. A summary receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the overall diagnostic performance. All the statistical analysis was performed by using STATA 12.0 and Meta-DiSc 1.4 software. A total of nine studies with 1214 subjects were included this meta-analysis. The pooled sensitivity, specificity, PLR, NLR and DOR were 0.54 [95% CI (confidence interval): 0.48–0.59], 0.97 (95% CI: 0.95–0.98), 12.13 (95% CI: 8.23–17.88), 0.36 (95% CI: 0.23–0.56) and 44.71 (95% CI: 22.30–89.63) respectively. The AUC was 0.96. Estimated positive and negative post-probability values for a SNPT prevalence of 20% were 82% and 7% respectively. No publication bias was identified. Current available evidence indicated that NAATs on BALF may play a role in diagnosing SNPT, whereas the results should be interpreted in parallel with clinical information of patients and the results of traditional tests. Further studies should be performed to confirm our findings.     

Development, validation and evaluation of a rapid PCR-nucleic acid lateral flow immuno-assay for the detection of Plasmodium and the differentiation between Plasmodium falciparum and Plasmodium vivax

ABSTRACT: BACKGROUND: Molecular tools are very sensitive and specific and could be an alternative for the diagnosis of malaria. The complexity and need for expensive equipment may hamper implementation and, therefore, simplifications to current protocols are warranted. METHODS: A PCR detecting the different Plasmodium species and differentiating between Plasmodium falciparum and Plasmodium vivax was developed and combined with a nucleic acid lateral flow immuno-assay (PCR-NALFIA) for amplicon detection. The assay was thoroughly evaluated for the analytical sensitivity and specificity in the laboratory, the robustness and reproducibility in a ring trial and accuracy and predictive value in a field trial. RESULTS: The analytical sensitivity and specificity were 0.978 (95% CI: 0.932-0.994) and 0.980 (95% CI: 0.924-0.997), respectively, and were slightly less sensitive for the detection of P. vivax than for P. falciparum. The reproducibility tested in three laboratories was very good (k = 0.83). This evaluation showed that the PCR machine used could influence the results. Accuracy was evaluated in Thailand and compared to expert microscopy and rapid diagnostic tests (RDTs). The overall and P. falciparum-specific sensitivity and specificity was good ranging from 0.86-1 and 0.95-0.98 respectively, compared to microscopy. Plasmodium vivax detection was better than the sensitivity of RDT, but slightly less than microscopy performed in this study. CONCLUSION: PCR-NALFIA is a sensitive, specific and robust assay able to identify Plasmodium species with good accuracy. Extensive testing including a ring trial can identify possible bottlenecks before implementation and is therefore essential to perform in additon to other evaluations.     

Core antigen tests for hepatitis C virus: a meta-analysis

Diagnosis and monitoring of hepatitis C virus (HCV) infection relies mainly on the detection of HCV antibodies and HCV RNA. HCV antibody test has a longer window period and is not applicable in the immunosuppressed population. Although HCV RNA test reduces the window period, it is still not widely recommended because of its high cost and requirement of specific equipment. HCV core antigen is another direct virological marker which has been investigated in recent years. HCV core antigen assay is as simple as the HCV antibodies assay and can detect HCV infection only 1 day delay compared to the HCV RNA assay. In order to evaluate the application of HCV core antigen test in HCV diagnosis and management, we performed this meta-analysis. Twenty five articles were finally included in meta-analysis. All statistical analyses were performed with MetaDisc 1.4 and Stata 11.0. The pooled sensitivity of HCV core antigen assay was 0.84 (95 % CI, 0.83-0.85), and the pooled specificity was 0.98 (95 % CI, 0.97-0.98). HCV core antigen assays may not displace HCV RNA assays to be a definitive diagnosis of HCV infection until now. Considering the higher sensitivity (0.926) and specificity (0.991) of subgroup, HCV-cAg detection is a promising method as a confirmatory test for HCV antibody positive, therapy-naive individuals. Explored by meta-regression and subgroup analysis, possible sources of heterogeneity of specificity was found, while the heterogeneity of sensitivity was still significant.     

Osteology of a slave burial population from Barbados,West Indies

A unique seventeenth–nineteenth century slave cemetery population from Newton plantation, Barbados, allows examination of craniodental characters in relation to ethnohistorical data. Age-at-death estimates suggest life expectancy at birth of 29 years and low infant mortality; historical demography, however, suggests life expectancy of 20 years and very high infant mortality. Tooth decay, bilateral tooth loss, periodontal disease, root hypercementosis, and severe enamel hypoplasia are high in frequency. The teeth yield evidence of such cultural practices as pipe-smoking and incisor mutilation. Several skeletal features reflect periodic near-starvation. Directional and fluctuating dental asymmetry, relative tooth size, and hypoplasia distribution suggest slaves experienced considerable weaning trauma; metabolic stress at this time exceeded that of prenatal and immediate postnatal periods. Odontometrics and dental and cranial nonmetric traits indicate that modern Blacks are intermediate between the ancestral slaves and modern Whites but more similar to the latter, suggesting effects of environmental covariance exceed those of genetic admixture. Nonmetric trait distributions show nonrandom patterns according to area of burial in the cemetery, a possible result of family segregation.     

Diagnostic Value of Mutation-Specific Antibodies for Immunohistochemical Detection of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer: A Meta-Analysis

Background

Various studies have assessed the diagnostic accuracy of EGFR mutation-specific antibodies in non-small cell lung cancer (NSCLC). We performed a meta-analysis of existing data to investigate the diagnostic value of mutation-specific antibodies for detection of EGFR mutations in NSCLC.

Methods

We systematically retrieved relevant studies from PubMed, Web of Knowledge, and Google Scholar. Data from studies that met the inclusion criteria were extracted for further exploration of heterogeneity, including calculation of the average sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and analysis of SROC(summary receiver operating characteristic) curves.

Results

Fifteen studies met our inclusion criteria. A summary of the meta-analysis of the efficacy of the anti-E746-A750 antibody was as follows: sensitivity, 0.60 (95% CI, 0.55–0.64); specificity, 0.98 (95% CI, 0.97–0.98); PLR, 33.50 (95% CI, 13.96–80.39); NLR, 0.39 (95% CI, 0.30–0.51) and DOR, 111.17 (95% CI, 62.22–198.63). A similar meta-analysis was performed for the anti-L858R antibody with results as follows: sensitivity, 0.76 (95% CI, 0.71–0.79); specificity, 0.96 (95% CI, 0.95–0.97); PLR, 24.42 (95% CI, 11.66–51.17); NLR, 0.22 (95% CI, 0.12–0.39) and DOR, 126.66 (95% CI, 54.60–293.82).

Conclusion

Immunohistochemistry alone is sufficient for the detection of EGFR mutations if the result is positive. Molecular-based analyses are necessary only if the anti-E746-A750 antibody results are negative. Immunohistochemistry seems more suitable for clinical screening for EGFR mutations prior to molecular-based analysis.     

Trimodal GSTT1 and GSTM1 genotyping assay by real-time PCR

The GSTT1 and GSTM1 genes are characterized by the existence of a GST*0 null allele responsible for a lack of enzyme activity, with the respective null genotypes GSTT1*0/0 and GSTM1*0/0. The three resulting genotypes (GSTs*1/1, *1/0 and *0/0) are associated with a trimodal distribution of glutathione-conjugator activity. Previous epidemiological studies have only evaluated the cancer risk associated with the GST null genotype relative to the two GST carrier genotypes (GSTs1*1/1 and *1/0). We developed GSTT1 and GSTM1 TaqMan real-time quantitative PCR assays to discriminate each of the three genotypes, with the albumin gene (ALB) as reference. The mean N(GSTT1*1/1) value was 1.0 (95% confidence interval 0.80-1.20). The mean N(GSTT1*1/0) value was 0.48 (95% CI 0.36-0.60). One (3.4%) of the 29 DNA samples yielded the GSTM1*1/1 genotype (N(GSTM1*1/1) = 1), a frequency in keeping with the Hardy-Weinberg distribution. The mean N(GSTM1*1/0) value was 0.50 (95% CI 0.42-0.58). All GSTT1*0/0 and GSTM1*0/0 samples yielded N(GST) values of 0 (Ct = 40); the frequencies of these genotypes (27.6% and 55.2%, respectively) were in keeping with published data. The GSTT1 and GSTM1 real-time PCR assays described here unambiguously discriminate each of the three existing genotypes which should be valuable for assessing the relative risk of cancer associated with each of the three GST genotypes.     

Sex differentials in frailty in medieval England

In most modern populations, there are sex differentials in morbidity and mortality that favor women. This study addresses whether such female advantages existed to any appreciable degree in medieval Europe. The analyses presented here examine whether men and women with osteological stress markers faced the same risks of death in medieval London. The sample used for this study comes from the East Smithfield Black Death cemetery in London. The benefit of using this cemetery is that most, if not all, individuals interred in East Smithfield died from the same cause within a very short period of time. This allows for the analysis of the differences between men and women in the risks of mortality associated with osteological stress markers without the potential confounding effects of different causes of death. A sample of 299 adults (173 males, 126 females) from the East Smithfield cemetery was analyzed. The results indicate that the excess mortality associated with several osteological stress markers was higher for men than for women. This suggests that in this medieval population, previous physiological stress increased the risk of death for men during the Black Death to a greater extent than was true for women. Alternatively, the results might indicate that the Black Death discriminated less strongly between women with and without pre‐existing health conditions than was true for men. These results are examined in light of previous analyses of East Smithfield and what is known about diet and sexually mediated access to resources in medieval England. Am J Phys Anthropol 143:285–297, 2010. © 2010 Wiley‐Liss, Inc.     

Bone traumas in late antique populations from Croatia

We present the results of the analyses of traumatic bone injuries in two Late Antique (3r to 5th century AD) skeletal samples from Croatia: Zadar--located on the eastern Adriatic coast, and a composite skeletal series from continental Croatia consisting of skeletons from Osijek, Vinkovci, Strbinci, and Zmajevac. The osteological series from continental Croatia are related to settlements located on, or near the Danubian military border, while Zadar--350 km to the west, is located deep in the territory of the Roman Empire. Numerous historical sources describe barbaric incursions, as well as large battles related to civil wars during the Late Antique period in continental Croatia. Conversely, there is no mention of similar events in the Zadar region. In accordance with these data our analysis tests the hypothesis that the inhabitants of continental Croatia were exposed to greater levels of violence than those living in Zadar. Analysis of bone traumas in the two series shows a similar, relatively high prevalence of long bone fractures in both samples, with a slightly higher frequency recorded in Zadar. Both series exhibit a high frequency of cranial injuries with, once again, higher frequencies recorded in the Zadar series. Additionally, two perimortem cranial fractures (one caused by a sword, the other by a blunt object) were observed in Zadar. Some of the recorded traumas in both samples resulted from accidents, but a number of injuries clearly resulted from intentional violence of lesser intensity. Further multidisciplinary research incorporating osteological, archaeological, and historical analyses is necessary to confirm the results obtained from these samples.     

Human gouty arthritis is associated with a distinct serum trace elemental profile

Homeostatic imbalance of essential trace elements is deeply involved in many pathophysiological states, especially in joint disorders such as gout. A total of 64 elements were measured in the serum samples in three regionally independent groups of patients with gouty arthritis (n = 100) and an age-matched healthy control group (n = 40) by inductively coupled plasma-mass spectrometry (ICP-MS). A distinct elemental profile of gouty arthritis encompassing significantly altered Li, Al, Ti, Fe, Cu, Se, Sr, Ta, Hg, Bi, Th, and U was obtained with a sensitivity of 0.97 (95% confidence interval (CI): 0.92-0.99) and a specificity of 0.95 (95% CI: 0.83-0.99) for gout diagnosis. An independent group of 52 subjects (39 gout patients and 13 healthy controls) was further used to validate the elemental signature, yielding a sensitivity of 1.00 (95% CI: 0.91-1.00) and a specificity of 1.00 (95% CI: 0.75-1.00) for gout prediction. It is also noteworthy that we were able to achieve ≥95.7% correct classification rate in both discovery and validation groups using only three elemental markers, Li, Al, and U. We also observed a good correlation between Li, Zn, and Cu and the other two risk factors, age and serum urate concentration, in gout patients. Our findings underscore that gouty arthritis possesses a unique elemental expression profile regardless of many other nutritional and environmental factors.