Growth of Neanderthal infants from Krapina (120-130 ka), Croatia.

Modern humans have a slow and extended period of childhood growth, but to what extent this ontogenetic pathway was present in Neanderthals is debated. Dental development, linked to the duration of somatic growth across modern primates, is the main source for information about growth and development in a variety of fossil primates, including humans. Studies of Neanderthal permanent teeth report a pace of development either similar to recent humans or relatively accelerated. Neanderthal milk teeth, which form and emerge before permanent teeth, provide an opportunity to determine which pattern was present at birth. Here we present a comparative study of the prenatal and early postnatal growth of five milk teeth from three Neanderthals (120 000-130 000 years ago) using virtual histology. Results reveal regions of their milk teeth formed quickly before birth and over a relatively short period of time after birth. Tooth emergence commenced towards the earliest end of the eruption schedules displayed by extant human children. Advanced dental development is consistent with expectations for Neanderthal infant feeding.

Mammalian Life History: Weaning and Tooth Emergence in a Seasonal World.

The young of toothed mammals must have teeth to reach feeding independence. How tooth eruption integrates with gestation, birth and weaning is examined in a life-history perspective for 71 species of placental mammals. Questions developed from high-quality primate data are then addressed in the total sample. Rather than correlation, comparisons focus on equivalence, sequence, the relation to absolutes (six months, one year), the distribution of error and adaptive extremes. These mammals differ widely at birth, from no teeth to all deciduous teeth emerging, but commonalities appear when infants transit to independent feeding. Weaning follows completion of the deciduous dentition, closest in time to emergence of the first permanent molars and well before second molars emerge. Another layer of meaning appears when developmental age is counted from conception because the total time to produce young feeding independently comes up against seasonal boundaries that are costly to cross for reproductive fitness. Mammals of a vast range of sizes and taxa, from squirrel monkey to moose, hold conception-to-first molars in just under one year. Integrating tooth emergence into life history gives insight into living mammals and builds a framework for interpreting the fossil record.

Improvement in chronic pelvic pain, orthostatic intolerance and interstitial cystitis symptoms after treatment of pelvic vein insufficiency.

OBJECTIVES: Comorbidities associated with venous origin chronic pelvic pain (VO-CPP) were evaluated pre and post venous treatment to assess change. MATERIALS AND METHODS: 45 women with VO-CPP were treated with venous stenting and/or embolization. Four surveys assessed symptoms pre- and post-treatment: IPPS (chronic pelvic pain), PUF (interstitial cystitis), OHQ (dysautonomia), and modified ROME III (IBS). Prevalence of joint hypermobility was investigated. RESULTS: Ages were 18-65. Pretreatment, 64% and 49% of women were in the severe range for PUF and OHQ, respectively. 40% and 56% met criteria for IBS and Ehlers-Danlos syndrome/Hypermobility Spectrum Disorder (EDS/HSD), respectively. 17eceived an iliac stent, 5 pelvic embolization, and 23 both. Post-treatment, average scores improved: IPPS (by 55%), PUF (34%), and OHQ (49%). Rome III improved only slightly. CONCLUSION: Pelvic pain, interstitial cystitis, and dysautonomia were frequently found with VO-CPP and improved after venous treatment. EDS/HSD and IBS were common in these women.

Nonpelvic comorbid symptoms of 45 patients with pain of pelvic venous origin, before and after treatment.

OBJECTIVE: To report the prevalence and severity of nonpelvic symptoms for patients with venous-origin chronic pelvic pain (VO-CPP) and to describe outcomes after pelvic vein stenting and embolization. METHODS: We retrospectively reviewed outcomes of 45 women with VO-CPP who underwent treatment with iliac vein stenting and/or embolization. Patients completed symptom-severity questionnaires before and after treatment that assessed for pelvic pain, and multiple other symptoms, including brain fog, anxiety, depression, musculoskeletal pain, fatigue, migraines and more. RESULTS: Patient age ranged from 18 to 65 years. The prevalence of common symptoms was as follows: migraines, 69%; brain fog, 76%; anxiety attacks, 58%; excess sweating, 64%; hip pain, 73%; diarrhea, 62%; constipation, 76%; and abdominal bloating, 82%. After treatment, most symptom scores improved by more than 50%; exceptions were excessive sweating (41% improvement) and bloating (47% improvement). Prevalence of individual symptoms that bundle into POTS ranged from 29% to 76%, where symptom improvement ranged from 23% to 59% after treatment. Overlapping individual symptoms characteristic of fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) were present in 64% to 82% of patients and all improved by 49% to 63% after treatment. CONCLUSIONS: Pelvic venous flow abnormality is linked causally to a spectrum of interrelated symptoms, of which many can be bundled into named syndromes of unknown cause. With catheter- based treatment of pelvic venous pooling, nonpelvic symptom and syndrome scores improved.

An online survey of pelvic congestion support group members regarding comorbid symptoms and syndromes.

OBJECTIVES: Patients with pelvic congestion syndrome (PCS) often report overlapping somatic symptoms and syndromes. The objective of this study was to explore the prevalence of co-existing symptoms and self-reported syndrome diagnoses among women with PCS and to inform future research hypotheses. METHODS: A brief online survey was offered to members of a PCS support group website. Responses were assessed for self-reported co-existing symptoms and formal diagnoses, including: chronic fatigue syndrome, fibromyalgia, postural tachycardia syndrome, irritable bowel syndrome, migraines, interstitial cystitis, and temporomandibular joint dysfunction. RESULTS: Of a total of 6000 members, there were 398 respondents; 232 (59%) had not yet been treated for PCS. Among these, the most prevalent co-existing symptoms were as follows: severe fatigue (72%), dizziness (63%), IBS symptoms (61%), brain fog (33%), migraines (49%), polyuria or dysuria (41%), excessive sweating (31%), TMJ pain (31%), and loose skin or lax joints (18%). These are much higher than reported for the general female population. The most commonly self-reported comorbid syndrome diagnoses for the overall group of 398 were: irritable bowel syndrome (29%), fibromyalgia (13%), spinal nerve problems (18%), interstitial cystitis (10%), postural tachycardia syndrome (9%), hypertension (11%), chronic fatigue syndrome (10%), and Ehlers-Danlos syndrome (6%). Other than with hypertension, these rates are variably higher than in the general population. CONCLUSION: Several self-reported co-existing symptoms and syndromes are more prevalent in members of a PCS support group relative to the reported prevalence in the general population. More formal investigation is warranted to evaluate this finding and to investigate potential etiologic links. Ehlers-Danlos Syndrome appears to be common in self identifying PCS women.

Mortality and the magnitude of the "wild effect" in chimpanzee tooth emergence.

Age of tooth emergence is a useful measure of the pace of life for primate species, both living and extinct. A recent study combining wild chimpanzees of the Taï Forest, Gombe, and Bossou by Zihlman et al. (2004) suggested that wild chimpanzees erupt teeth much later than captives, bringing into question both comparisons within the hominin fossil record and assessment of chimpanzees. Here, we assess the magnitude of the "wild effect" (the mean difference between captive and wild samples expressed in standard deviation units) in these chimpanzees. Tooth emergence in these wild individuals is late, although at a more moderate level than previously recorded, with a mean delay conservatively estimated at about 1 SD compared to the captive distributions. The effect rises to 1.3 SD if we relax criteria for age estimates. We estimate that the mandibular M1 of these wild chimpanzees emerges at about 3 (2)/(3)-3 ¾ years of age. An important point, often ignored, is that these chimpanzees are largely dead of natural causes, merging the effect of living wild with the effect of early death. Evidence of mortality selection includes, specifically: younger deaths appear to have been more delayed than the older in tooth emergence, more often showed evidence of disease or debilitation, and revealed a higher occurrence of dental anomalies. Notably, delay in tooth emergence for live-captured wild baboons appears lower in magnitude (ca. 0.5 SD) and differs in pattern. Definitive ages of tooth emergence times in living wild chimpanzees must be established from the study of living animals. The fossil record, of course, consists of many dead juveniles; the present study has implications for how we evaluate them.

Imaging findings of pelvic venous insufficiency in patients with postural orthostatic tachycardia syndrome.

OBJECTIVES: Some patients with postural orthostatic tachycardia syndrome (POTS) demonstrate improved dysautonomic symptoms following treatment for pelvic venous insufficiency (PVI). This study assessed the prevalence of significant left common iliac vein (LCIV) compression in POTS patients. METHODS: Radiologists retrospectively reviewed CT images of pelvic veins for 216 women (191 with POTS and 25 age-comparable controls).Quantitative vascular analysis identified percent-diameter compression of the LCIV by the right common iliac artery. Significant LCIV compression was defined as >50%. RESULTS: Significant LCIV compression was found in 69% (131/191) of females with POTS versus 40% (10/25) in controls. The hypothesis that venous compression and presence of POTS are independent was rejected (p = .005). CONCLUSIONS: Significant LCIV compression was noted in a majority of female POTS patients, suggesting that incidence of iliac venous obstruction may be higher than the general population. Patients with POTS and symptoms of PVI may benefit from assessment for venous outflow obstruction.

Bias and accuracy of age estimation using developing teeth in 946 children.

Developing teeth are used to assess maturity and estimate age in several disciplines. The aim of the study was to determine which of the most well known dental age estimation methods was best at estimating age. The target sample of dental radiographs (N = 946, ages 3­16) was described by Maber et al. (Forensic Sci Int 159 (2006) S68­S73). Seven mandibular permanent teeth (I1­M2) were assessed, and dental age was calculated using four dental maturity scales and fifteen methods that use data for individual teeth. The mean difference between dental age and real age was calculated (bias) as well as several other measures of accuracy (mean/median absolute difference, percentage aged to within six months and to within 10% of real age). Most methods estimated age with significant bias and standard deviation of bias ranged from 0.86 to 1.03 years. Analysis by age group showed most methods over-aged younger children, and considerably under-aged older children. The method that performed best was the dental maturity scale of Willems et al. (J Forensic Sci 46 (2001) 893­895) with bias of −0.14 ± 0.86 years (N = 827), mean absolute difference of 0.66 years, 71% aged to 10% or less of age, and 49% aged to within six months. Two individual teeth, P2 and M2, estimated age with bias not significantly different to zero for most formation stages using methods based on a large reference sample (L9a Demirjian stages) and a uniform age distribution (N25a Moorrees stages). Standard deviation of bias was least for early crown stages and most for late root stages. Methods that average ages for individual teeth improve if schedules for 'mean age entering a stage' are adjusted for prediction. Methods that directly calculate 'mean age within stage' can be improved by drawing from a uniform age distribution.

Sequence of emergence of the permanent teeth in Macaca, Pan, Homo, and Australopithecus: Its evolutionary significance.

There are two main questions about the sequence of emergence of the permanent teeth in humans: 1) Why is there so much variation in sequence within human populations? (2) What is the adaptive or evolutionary significance of emergence sequence? Here, the human condition is considered by comparing us to other living primates and to our evolutionary past and considered in the light of Schultz's hypothesis that sequence of tooth emergence is adapted to rate of postnatal growth (Schultz AH. In JM Tanner (ed.) Human Growth, pp 1-20, 1960). Frequencies of individual pairwise sequences (e.g., M1 I1 vs. I1 M1 ) in the emergence of the permanent dentition are described for N = 110 Macaca nemestrina, and compared to N = 157 Pan troglodytes and ≥6,000 Homo sapiens. In addition, sequences of gingival emergence are reconstructed for Australopithecus and early Homo. Trends observed across these catarrhine primates suggest that sequence and variability in sequence can be understood by a simple model of adaptation of tooth emergence to growth rate. As rate of postnatal growth slows, molars drift to later positions in sequence, either by always emerging late in sequence, or by varying in the direction of late emergence. "Augmented sequences" (sequences written with notations about variability) are important in recognizing evolutionary trends; further, they often alter perception of similarities and differences among taxa. Although samples are small, Australopithecus africanus resembles the rapidly developing genera Macaca and Pan more than it resembles Homo sapiens. © 1994 Wiley-Liss, Inc.

Evolution of the human life cycle.

Social mammals have three basic stages of postnatal development: infant, juvenile, and adult. Some species also have a brief female post-reproductive stage. The human life cycle, however, is best described by five stages: infant, child, juvenile, adolescent, and adult. Women in both traditional and industrial societies may also have a long post-reproductive stage. Analyses of bones and teeth of early hominids who died as subadults suggest that the evolution of the new life stages of childhood and adolescence are not of ancient origin. The current human pattern evolved after the appearance of Homo erectus. It is possible that evidence for the existence of the post-reproductive stage for women will also be recoverable from the fossil record because the hormonal changes associated with menopause have profound effects on bone density and histology of tubular bones. It is hypothesized that the new life stages of the human life cycle represent feeding and reproductive specializations of the genus Homo. © 1996 Wiley-Liss, Inc.

Complete primate skeleton from the Middle Eocene of Messel in Germany: morphology and paleobiology.

BACKGROUND: The best European locality for complete Eocene mammal skeletons is Grube Messel, near Darmstadt, Germany. Although the site was surrounded by a para-tropical rain forest in the Eocene, primates are remarkably rare there, and only eight fragmentary specimens were known until now. Messel has now yielded a full primate skeleton. The specimen has an unusual history: it was privately collected and sold in two parts, with only the lesser part previously known. The second part, which has just come to light, shows the skeleton to be the most complete primate known in the fossil record. METHODOLOGY/PRINCIPAL FINDINGS: We describe the morphology and investigate the paleobiology of the skeleton. The specimen is described as Darwinius masillae n.gen. n.sp. belonging to the Cercamoniinae. Because the skeleton is lightly crushed and bones cannot be handled individually, imaging studies are of particular importance. Skull radiography shows a host of teeth developing within the juvenile face. Investigation of growth and proportion suggest that the individual was a weaned and independent-feeding female that died in her first year of life, and might have attained a body weight of 650-900 g had she lived to adulthood. She was an agile, nail-bearing, generalized arboreal quadruped living above the floor of the Messel rain forest. CONCLUSIONS/SIGNIFICANCE: Darwinius masillae represents the most complete fossil primate ever found, including both skeleton, soft body outline and contents of the digestive tract. Study of all these features allows a fairly complete reconstruction of life history, locomotion, and diet. Any future study of Eocene-Oligocene primates should benefit from information preserved in the Darwinius holotype. Of particular importance to phylogenetic studies, the absence of a toilet claw and a toothcomb demonstrates that Darwinius masillae is not simply a fossil lemur, but part of a larger group of primates, Adapoidea, representative of the early haplorhine diversification.

New protocetid whale from the middle eocene of pakistan: birth on land, precocial development, and sexual dimorphism.

BACKGROUND: Protocetidae are middle Eocene (49-37 Ma) archaeocete predators ancestral to later whales. They are found in marine sedimentary rocks, but retain four legs and were not yet fully aquatic. Protocetids have been interpreted as amphibious, feeding in the sea but returning to land to rest. METHODOLOGY/PRINCIPAL FINDINGS: Two adult skeletons of a new 2.6 meter long protocetid, Maiacetus inuus, are described from the early middle Eocene Habib Rahi Formation of Pakistan. M. inuus differs from contemporary archaic whales in having a fused mandibular symphysis, distinctive astragalus bones in the ankle, and a less hind-limb dominated postcranial skeleton. One adult skeleton is female and bears the skull and partial skeleton of a single large near-term fetus. The fetal skeleton is positioned for head-first delivery, which typifies land mammals but not extant whales, evidence that birth took place on land. The fetal skeleton has permanent first molars well mineralized, which indicates precocial development at birth. Precocial development, with attendant size and mobility, were as critical for survival of a neonate at the land-sea interface in the Eocene as they are today. The second adult skeleton is the most complete known for a protocetid. The vertebral column, preserved in articulation, has 7 cervicals, 13 thoracics, 6 lumbars, 4 sacrals, and 21 caudals. All four limbs are preserved with hands and feet. This adult is 12% larger in linear dimensions than the female skeleton, on average, has canine teeth that are 20% larger, and is interpreted as male. Moderate sexual dimorphism indicates limited male-male competition during breeding, which in turn suggests little aggregation of food or shelter in the environment inhabited by protocetids. CONCLUSIONS/SIGNIFICANCE: Discovery of a near-term fetus positioned for head-first delivery provides important evidence that early protocetid whales gave birth on land. This is consistent with skeletal morphology enabling Maiacetus to support its weight on land and corroborates previous ideas that protocetids were amphibious. Specimens this complete are virtual 'Rosetta stones' providing insight into functional capabilities and life history of extinct animals that cannot be gained any other way.