Prediction of microcephaly at birth using three reference ranges for fetal head circumference: can we improve prenatal diagnosis?

OBJECTIVE: To evaluate the prediction of microcephaly at birth (micB) using established and two new reference ranges for fetal head circumference (HC) and to assess whether integrating additional parameters can improve prediction. METHODS: Microcephaly in utero was defined as a fetal HC 3SD below the mean for gestational age according to Jeanty et al.'s reference range. The records of cases with fetal microcephaly (Fmic) were evaluated for medical history, imaging findings, biometry and postnatal examination/autopsy findings. Microcephaly was confirmed at birth (micB) by an occipitofrontal circumference (OFC) or a brain weight at autopsy 2SD below the mean for gestational age. The new INTERGROWTH-21(st) Project and a recent Israeli reference for fetal growth were applied for evaluation of the Fmic positive predictive value (PPV) for diagnosis of micB cases. Optimal HC cut-offs were determined for each of the new references with the aim of detecting all micB cases whilst minimizing the number of false positives found to have a normal HC at birth. We also assessed the difference between the Z-scores of the prenatal HC and the corresponding OFC at birth, the frequency of small-for-gestational age (SGA), decreased HC/abdominal circumference (AC) and HC/femur length (FL) ratios, the prevalence of associated malformations and family history. RESULTS: Forty-two fetuses were diagnosed as having Fmic according to the Jeanty reference, but micB was confirmed in only 24 (PPV, 57.1%). The optimal INTERGROWTH and Israeli reference HC cut-offs for micB diagnosis were mean - 3SD and mean - 2.3SD, resulting in a statistically non-significant improvement in PPV to 61.5% and 66.7%, respectively. The presence of a family history of microcephaly, SGA, associated malformations and application of stricter HC cut-offs resulted in a higher PPV of micB, although not statistically significant and with a concurrent increase in the number of false-negative results. The deviation of the HC from the mean, by all references, was significantly larger compared with the actual deviation of the OFC at birth, with mean differences between the corresponding Z-scores of -1.15, -1.95 and -0.74 for the Jeanty, INTERGROWTH and Israeli references, respectively. CONCLUSIONS: The evaluated reference ranges all result in considerable over-diagnosis of fetal microcephaly. The use of the two new HC reference ranges did not significantly improve micB prediction compared with that of Jeanty et al., whilst use of additional characteristics and stricter HC cut-offs could improve the PPV with an increase in false negatives. The postnatal OFC deviates significantly less from the mean compared with the prenatal HC, and we propose that adjustment for this would enable better prediction of the actual OFC deviation at birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Application of a novel prenatal vertical cranial biometric measurement can improve accuracy of microcephaly diagnosis in utero.

OBJECTIVE: To construct a reference range for a new vertical measurement of the fetal head and to assess whether its combination with fetal head circumference (HC) can prevent the misdiagnosis of microcephaly in fetuses with an acrocephalic-like head deformation. METHODS: A new vertical cranial biometric measurement was defined: the foramen magnum-to-cranium distance (FCD), measured between the foramen magnum and the upper inner cranial border along the posterior wall of the brainstem. The measurement was performed in a precise mid-sagittal plane using a three-dimensional multiplanar display of a sagittally acquired sonographic volume of the fetal head. The normal reference range was developed by measuring 396 healthy fetuses of low-risk singleton pregnancies between 15 and 40 gestational weeks. This reference was applied to 25 fetuses with microcephaly diagnosed prenatally (Fmic) based on HC ≥ 3 SD below the mean for gestational age. We determined an optimal FCD cut-off for combination with HC to detect all cases found with microcephaly at birth (micB), while excluding the fetuses with normal head circumference at birth (NHCB), who were described postnatally as having an acrocephalic-like cranial deformation. RESULTS: In the healthy singleton fetuses, FCD increased with gestational age, with a quadratic equation providing an optimal fit to the data (adjusted R(2) = 0.934). The measurement could be assessed in 95.2% of cases. Of the 25 cases diagnosed with Fmic prenatally, on the basis of HC alone, 14 were micB and 11 were NHCB. We observed FCD below the mean - 2SD for gestational age in all 14 micB cases, but in only four of the 11 NHCB cases (P < 0.003). An acrocephalic-like cranial deformation was described at birth in five of the seven NHCB cases with normal FCD. The mean ± SD FCD Z-score of the micB cases was significantly lower (P < 0.001) than that of the false-positive ones: -3.85 ± 0.96 SD and -1.59 ± 1.45 SD, respectively. Based on HC measurement alone, the positive predictive value (PPV) was 56%. Combination of the HC and FCD criteria raised the PPV to 78%, decreasing the number of false positives from 11 to four, without missing any of the 14 micB cases. CONCLUSIONS: Fetal vertical cranial biometric assessment in the mid-sagittal plane is feasible and correlates well with gestational age. In our series, a vertical cranial deformation was a frequent cause of a false Fmic diagnosis made on the basis of HC alone. Combination of the new vertical cranial biometric measurement with HC measurement can exclude these cases and thus improve diagnostic accuracy for Fmic. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Disc in flames: Roles of TNF-α and IL-1ß in intervertebral disc degeneration.

The intervertebral disc is an important mechanical structure that allows range of motion of the spinal column. Degeneration of the intervertebral disc--incited by aging, traumatic insult, genetic predisposition, or other factors--is often defined by functional and structural changes in the tissue, including excessive breakdown of the extracellular matrix, increased disc cell senescence and death, as well as compromised biomechanical function of the tissue. Intervertebral disc degeneration is strongly correlated with low back pain, which is a highly prevalent and costly condition, significantly contributing to loss in productivity and health care costs. Disc degeneration is a chronic, progressive condition, and current therapies are limited and often focused on symptomatic pain relief rather than curtailing the progression of the disease. Inflammatory processes exacerbated by cytokines tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) are believed to be key mediators of disc degeneration and low back pain. In this review, we describe the contributions of TNF-α and IL-1ß to changes seen during disc degeneration at both cellular and tissue level, as well as new evidence suggesting a link between infection of the spine and low back pain, and the emerging therapeutic modalities aimed at combating these processes.

Fetal posterior fossa dimensions: normal and anomalous development assessed in mid-sagittal cranial plane by three-dimensional multiplanar sonography.

OBJECTIVES: To construct nomograms of the dimensions of the fetal posterior fossa (PF), assessed in the mid-sagittal plane in the second and third trimesters, and to assess how measurements from fetuses with PF abnormalities deviate from our normal ranges. METHODS: This was a prospective cross-sectional study of 378 healthy fetuses in low-risk singleton pregnancies between 15 and 35 weeks. PF size was evaluated in the mid-sagittal plane of the fetal head using three-dimensional multiplanar reconstruction (3D-MPR). The borders of the PF were defined from the clivus to the tentorium (clivotentorial distance, CTD) and from the occipital bone to the level of the upper mesencephalic edge (tecto-occipital distance, TOD), and the posterior fossa area (PFA) and perimeter (PFP) were assessed. Growth charts were produced. Thirty-nine fetuses diagnosed with PF malformations were analyzed by calculating the z-scores of PFA, PFP, TOD and CTD, relative to the developed nomograms. RESULTS: Of the 378 healthy fetuses initially included, there were 281 with adequate visualization of the PF borders; i.e. PF mid-sagittal plane morphometry was feasible in 74.3% of cases. There was a linear relationship between each of PFA, PFP, TOD and CTD, and gestational age, with Pearson correlation coefficients of 0.97, 0.97, 0.96 and 0.95, respectively (P < 0.001 for each). Chiari II malformation (CM-II) and Dandy-Walker malformation (DWM) were associated with the greatest difference in PF size compared with normal; PFA z-scores exceeded 2.6 in all five DWM cases and were below -2.66 in all 11 CM-II cases. CONCLUSIONS: Sonographic evaluation of fetal PF size in the mid-sagittal plane is feasible. Our constructed nomograms provide reference data that may be helpful when evaluating PF congenital malformations.

Assessment of fetal midbrain and hindbrain in mid-sagittal cranial plane by three-dimensional multiplanar sonography. Part 2: application of nomograms to fetuses with posterior fossa malformations.

OBJECTIVES: To apply fetal midbrain (MB) and hindbrain (HB) nomograms, developed using three-dimensional multiplanar sonographic reconstruction (3D-MPR) in the mid-sagittal cranial plane, to fetuses with known posterior fossa malformations. METHODS: In this retrospective study we examined sonographic volumes obtained by sagittal acquisition in 43 fetuses diagnosed with posterior fossa abnormalities and evaluated in the mid-sagittal cranial plane, using 3D-MPR, the following: MB parameters tectal length (TL) and anteroposterior midbrain diameter (APMD), and HB parameters anteroposterior pons diameter (APPD), superoinferior vermian diameter (SIVD) and anteroposterior vermian diameter (APVD). Fetuses were grouped, according to malformation, into eight categories: cobblestone malformation complex (CMC, n = 3), Chiari-II malformation (C-II, n = 7), pontocerebellar hypoplasia (PCH, n = 2), rhombencephalosynapsis (RES, n = 4), Dandy-Walker malformation (n = 8), vermian dysgenesis (VD, n = 7), persistent Blake's pouch cyst (n = 6) and megacisterna magna (n = 6). In each case and for each subgroup, the MB-HB biometric parameters and their z-scores were evaluated with reference to our new nomograms. RESULTS: The new MB-HB nomograms were able to identify the brainstem and vermian anomalies and differentiate fetuses with MB-HB malformations from those with isolated enlarged posterior fossa cerebrospinal fluid spaces. Use of the nomograms enabled detection of an elongated tectum in fetuses with CMC, C-II and RES, and a flattened pontine belly in cases of CMC, PCH and VD. In the fetuses with VD, the nomograms enabled division into three distinctive groups: (1) those with small SIVD and APVD, (2) those with normal SIVD but small APVD, and (3) those with small SIVD but normal APVD. CONCLUSIONS: Application of our new reference data, that for the first time include the MB, enables accurate diagnosis of brain malformations affecting the MB and HB and makes possible novel characterization of previously described features of posterior fossa anomalies.

Assessment of fetal midbrain and hindbrain in mid-sagittal cranial plane by three-dimensional multiplanar sonography. Part 1: comparison of new and established nomograms.

OBJECTIVE: To construct nomograms for fetal midbrain (MB) and hindbrain (HB) dimensions, assessed in the mid-sagittal cranial plane by three-dimensional multiplanar sonographic reconstruction (3D-MPR). METHODS: This was a prospective cross-sectional study of 334 healthy fetuses in low-risk singleton pregnancies between 16 and 35 gestational weeks. All sonographic volumes were obtained by sagittal acquisition. The following MB and HB parameters were evaluated in the mid-sagittal cranial plane using 3D-MPR: MB parameters tectal length (TL) and anteroposterior midbrain diameter (APMD), and HB parameters anteroposterior pons diameter (APPD), superoinferior vermian diameter (SIVD), anteroposterior vermian diameter (APVD) and anteroposterior diameter of the fourth ventricle (APDFV). The measurements were presented as growth charts according to gestational age. RESULTS: MB and HB biometry were best assessed between 19 and 29 weeks. During this period, adequate visualization was achieved for successful measurement of TL in 90.9% of cases, APMD in 86.6%, APPD in 73.7%, SIVD in 74.2%, APVD in 71% and APDFV in 71%. There was a linear growth pattern, with Pearson correlation coefficients of 0.79 for TL, 0.88 for APMD, 0.91 for APPD, 0.95 for SIVD, 0.88 for APVD and 0.88 for APDFV (P < 0.0001 for each). The mean intra- and interobserver variations for the MB measurements and vermian diameters ranged between 4.3% and 9%. APPD and APDFV showed highest mean variations: 9.0% and 19.4% (intraobserver) and 11.6% and 17.7% (interobserver), respectively. CONCLUSION: We present new nomograms for assessment of the fetal MB and HB using 3D-MPR in the mid-sagittal cranial plane. To our knowledge, these are the first proposed nomograms for fetal MB dimensions.

Characterization of NCI-H295R cells as an in vitro model of hyperaldosteronism.

In depth analysis of key molecular mechanisms involved in functional autonomy of aldosterone secretion is hampered by the lack of tumor cell lines that reflect functional characteristics of aldosterone producing adenomas. Herein, we describe the characteristics of the adrenocortical carcinoma cell line NCI-H295R and its suitability as a model of hyperaldosteronism in relation to different culture conditions. Steroid profiling revealed that NCI-H295R cells predominantly secrete cortisol, while aldosterone and other steroids are released at much lower concentrations. However, aldosterone output specifically increased in response to different stimuli such as ACTH and angiotensin II, and in particular to potassium in a dose dependent manner. NCI-H295R cells readily formed spheroids under specific culture conditions, a method widely used for the enrichment of progenitor cells. Unexpectedly, spheroid cells excelled with higher aldosterone concentration and higher expression levels of the steroidogenic enzymes StAR, 3ßHSD, CYP17, SF-1, and the MC2-receptor. Further investigations revealed that this phenomenon is mainly attributed to epithelial growth factor (EGF) and particularly fibroblast growth factor (FGF), which are both essential ingredients in the spheroid culture medium. Aldosterone release under the combinatory influence of EGF and FGF was not higher than the effect of FGF alone. Spheroid growth per se, therefore, does not ensure an enrichment of less differentiated cell types in this cell line.

Sonographic imaging of fetal tympanic rings.

OBJECTIVE: To examine the feasibility of ultrasonographic imaging of fetal tympanic rings. METHODS: This was an observational cohort study of 80 healthy fetuses in low-risk pregnancies, divided into four gestational-age subgroups (12, 16, 23 and 32 weeks), each comprising 20 consecutive fetuses. Tympanic ring visualization was achieved by two-dimensional and three-dimensional (3D) sonography. A standard algorithm for tympanic ring examination was constructed using 3D multiplanar reconstruction. The volume acquisition plane was directed to the inferolateral aspect of the fetal temporal bone. Transvaginal scans were carried out in the 12-week and 16-week subgroups, and transabdominal scans in the 23-week and 32-week subgroups. Study parameters included the inferomedial inclination angle (IMIA) of the tympanic ring relative to the vertical skull axis, the anteromedial inclination angle (AMIA) of the tympanic ring relative to the anteroposterior skull axis and the longest (LTRD) and shortest (STRD) tympanic ring diameter, the latter measured perpendicular to the LTRD. The feasibility of tympanic ring demonstration was assessed in each gestational-age subgroup. RESULTS: Tympanic rings appeared as round-oval, thin, echogenic structures in a plane tangential to the inferolateral surface of the fetal skull below the inferior border of the squamous part of the temporal bone. Higher demonstration rates were achieved in the 16-week and 23-week subgroups (90% and 80%, respectively) than in the others. LTRD and STRD each showed a linear correlation with gestational age (r = 0.96 for both measurements; P < 0.01). Mean IMIA ranged from 41.0 to 60.4° and mean AMIA from 17.3 to 23.4° across the different gestational-age subgroups. The malleal manubrium was observed only in examinations in the second half of pregnancy, appearing as a bright echo within the upper area of the tympanic ring in 56% (9/16) and 82% (9/11) of cases with tympanic ring imaging appropriate for measurement of the study parameters in the 23-week and 32-week subgroups, respectively. CONCLUSION: This is the first report of sonographic imaging of fetal tympanic rings and shows that this is feasible in the second trimester. We discuss the possible implications of our findings for the prenatal diagnosis of congenital hearing loss.

Molecular engineering of an orthopaedic implant: from bench to bedside.

The use of metallic implants has revolutionised the practice of orthopaedic surgery. While the safety and biocompatibility of these devices are excellent, a small percentage becomes infected. These infections are due to the formation of a biofilm that harbours bacteria encased in a complex extracellular matrix. The matrix serves as a barrier to immune surveillance as well as limiting the biocidal effects of systemic and local antibiotics. The objective of the review is to describe a novel approach to controlling implant infection using an antibiotic that is linked to titanium through a self-assembled monolayer of siloxy amines. We show that the hybrid-engineered surface is stable, biocompatible and resists colonisation by bacterial species most commonly associated with implant-related infections. Studies with rodent bone infection models suggest that the engineered titanium surface prevents bone infection. Results of a very recent investigation utilising a sheep model of infection indicate that the titanium-tethered antibiotic controls infection without compromising bone formation and remodelling. From all of these perspectives, the tethered antibiotic holds promise of providing a novel and practical approach to reducing implant-associated infections.

Aldosterone producing adrenal adenomas are characterized by activation of calcium/calmodulin-dependent protein kinase (CaMK) dependent pathways.

Primary aldosteronism is the most prevalent cause of secondary hypertension. However, insights in pathophysiological mechanisms resulting in autonomous aldosterone secretion are limited. Although transcriptional regulators of aldosterone synthase (CYP11B2) including calcium-binding calmodulin kinase (CaMK) dependent pathways have been defined in vitro, it remains uncertain whether these mechanisms play a role in the context of dysregulated steroidogenesis in aldosterone producing adrenadenomas. Thus, we compared expression and activation of key components of CaMK pathways in aldosterone producing adenomas (APAs) with normal adrenals glands (NAGs). As expected, aldosterone synthase expression in APAs was significantly higher in comparison to NAGs, suggesting transcriptional activation as a contributing factor of aldosterone excess. Along the same line, CaMKI was significantly upregulated in APAs on the mRNA and protein level. Furthermore, immunohistochemistry revealed nuclear localization of CaMKI in these tumors. The phosphorylation of CREB, a target protein for CaMKI was increased, which could represent a further stimulation of aldosterone synthase transcription. In summary, this study provides indirect evidence for a causative involvement of the CaM kinase signaling pathway in human aldosterone producing adenomas.

TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc.

The central region of the intervertebral disc (IVD) is rich in proteoglycans, leading to a hyperosmotic environment, which fluctuates with daily loading. The cells of the nucleus pulposus (NP cells) have adapted to this environment via the function of tonicity enhancer binding protein (TonEBP), and NP cells have been shown to express several water channels known as aquaporins (AQP). We have previously shown that AQP1 and 5 decrease during IVD degeneration. Here, the regulation of AQP1 and 5 by hyperosmotic conditions and the role of TonEBP in this regulation was investigated. AQP1 and 5 gene expression was upregulated by hyperosmotic conditions mimicking the osmolality of the healthy IVD, which was abrogated by TonEBP knockdown. Furthermore, AQP1 and 5 immunopositivity was significantly reduced in TonEBPΔ/Δ E17.5 mice when compared with wildtype controls, indicating in vivo expression of AQP1 and 5 is controlled at least in part by TonEBP. This hyperosmotic regulation of AQP1 and 5 could help to explain the decreased AQP1 and 5 expression during degeneration, when the osmolality of the NP decreases. Together this data suggests that TonEBP-regulated osmo-adaptation may be disrupted during IVD degeneration when the expression of both AQPs is reduced.

Regulated production of mineralization-competent matrix vesicles in hypertrophic chondrocytes.

Matrix vesicles have a critical role in the initiation of mineral deposition in skeletal tissues, but the ways in which they exert this key function remain poorly understood. This issue is made even more intriguing by the fact that matrix vesicles are also present in nonmineralizing tissues. Thus, we tested the novel hypothesis that matrix vesicles produced and released by mineralizing cells are structurally and functionally different from those released by nonmineralizing cells. To test this hypothesis, we made use of cultures of chick embryonic hypertrophic chondrocytes in which mineralization was triggered by treatment with vitamin C and phosphate. Ultrastructural analysis revealed that both control nonmineralizing and vitamin C/phosphatetreated mineralizing chondrocytes produced and released matrix vesicles that exhibited similar round shape, smooth contour, and average size. However, unlike control vesicles, those produced by mineralizing chondrocytes had very strong alkaline phosphatase activity and contained annexin V, a membrane-associated protein known to mediate Ca2+ influx into matrix vesicles. Strikingly, these vesicles also formed numerous apatite-like crystals upon incubation with synthetic cartilage lymph, while control vesicles failed to do so. Northern blot and immunohistochemical analyses showed that the production and release of annexin V-rich matrix vesicles by mineralizing chondrocytes were accompanied by a marked increase in annexin V expression and, interestingly, were followed by increased expression of type I collagen. Studies on embryonic cartilages demonstrated a similar sequence of phenotypic changes during the mineralization process in vivo. Thus, chondrocytes located in the hypertrophic zone of chick embryo tibial growth plate were characterized by strong annexin V expression, and those located at the chondro-osseous mineralizing border exhibited expression of both annexin V and type I collagen. These findings reveal that hypertrophic chondrocytes can qualitatively modulate their production of matrix vesicles and only when induced to initiate mineralization, will release mineralization-competent matrix vesicles rich in annexin V and alkaline phosphatase. The occurrence of type I collagen in concert with cartilage matrix calcification suggests that the protein may facilitate crystal growth after rupture of the matrix vesicle membrane; it may also offer a smooth transition from mineralized type II/type X collagen-rich cartilage matrix to type I collagen-rich bone matrix.

Matrix GLA protein is a developmental regulator of chondrocyte mineralization and, when constitutively expressed, blocks endochondral and intramembranous ossification in the limb.

Matrix GLA protein (MGP), a gamma-carboxyglutamic acid (GLA)-rich, vitamin K-dependent and apatite-binding protein, is a regulator of hypertrophic cartilage mineralization during development. However, MGP is produced by both hypertrophic and immature chondrocytes, suggesting that MGP's role in mineralization is cell stage-dependent, and that MGP may have other roles in immature cells. It is also unclear whether MGP regulates the quantity of mineral or mineral nature and quality as well. To address these issues, we determined the effects of manipulations of MGP synthesis and expression in (a) immature and hypertrophic chondrocyte cultures and (b) the chick limb bud in vivo. The two chondrocyte cultures displayed comparable levels of MGP gene expression. Yet, treatment with warfarin, a gamma-carboxylase inhibitor and vitamin K antagonist, triggered mineralization in hypertrophic but not immature cultures. Warfarin effects on mineralization were highly selective, were accompanied by no appreciable changes in MGP expression, alkaline phosphatase activity, or cell number, and were counteracted by vitamin K cotreatment. Scanning electron microscopy, x-ray microanalysis, and Fourier-transform infrared spectroscopy revealed that mineral forming in control and warfarin-treated hypertrophic cell cultures was similar and represented stoichiometric apatite. Virally driven MGP overexpression in cultured chondrocytes greatly decreased mineralization. Surprisingly, MGP overexpression in the developing limb not only inhibited cartilage mineralization, but also delayed chondrocyte maturation and blocked endochondral ossification and formation of a diaphyseal intramembranous bone collar. The results show that MGP is a powerful but developmentally regulated inhibitor of cartilage mineralization, controls mineral quantity but not type, and appears to have a previously unsuspected role in regulating chondrocyte maturation and ossification processes.

Future sources of organic raw materials.

Industrial organizations, academic institutions, and national governments should agree on the cooperative roles each will play in planning the decadesahead raw materials needs of the chemical industry, which is vital to a modern, international economic system. The raw material future of the industry depends as much on political and social concerns as it does on technical and economic considerations. The generation in charge now cannot in good conscience go on consuming the world's supply of hydrocarbons and not acknowledge a duty to generations that will follow.

Resonance rotation of venus.

Combination of two types of radar data shows the orbital plane and equator of Venus to be included by less than 2 degrees, and the sidereal rotation period to be 243.09 +/- 0.18 days (retrograde)-remarkably close to the 243.16-day period for which the spin would be in resonance with the relative orbital motions of Earth and Venus. In this resonance, Venus would make, on average, four axial rotations as seen by an Earth observer between successive close approaches of the two planets. Estimates of the instantaneous spin period, accurate within about 0.01 day, would provide important information on the difference of Venus's equatorial moments of inertia, on their orientation, and on the magnitude of the tidal torque exerted on Venus by the sun.

New method for the detection of light deflection by solar gravity.

The prediction of Einstein's theory of general relativity that light will be deflected by the sun may be tested by sending radio waves from the earth to Venus or Mercury when either passes behind the sun and detecting the echoes with a radar interferometer.

Last of the west ford dipoles.

Radar measurements confirm that the several hundred million individually orbiting West Ford dipoles reentered the lower atmosphere in precise accord with predictions. Calculations indicate that these tiny copper wires survived reentry and floated gently back to Earth; unfortunately,the probability of finding one is minuscule. Some dipole clusters remain in orbit but almost all should return to Earth within the next 2 years.

Is the sun shrinking?

Observations of 23 transits of Mercury in front of the sun between 1736 and 1973 show no indication of any significant change in the diameter of the sun. Regression analysis yields a decrease of the angular diameter, as viewed from the earth, of under 0.3 arc second per century (> 90 percent confidence limit). This limit is incompatible with the 2 arc seconds per century decrease obtained by Eddy for the equatorial diameter from direct observations made at the Greenwich Observatory and at the U.S. Naval Observatory.

Scientific uses of pulsars.

The recently discovered celestial sources of pulsed radio energy can be used to test general relativity, to study the solar corona, and to determine the earth's orbit and ephemeris time. The vector positions and transverse velocities of pulsars can be measured with radio interferometers; in combination with pulse-arrival-time data, the distance determination will yield the average interstellar electron density.

Infection of normal human epithelial cells by Epstein-Barr virus.

Primary cultures of epithelial cells were grown from the tonsils and adenoids of patients with diseases not related to Epstein-Barr virus. The cells could not be infected by Epstein-Barr virus. Fluorescein-labeled Epstein-Barr virus and a cytofluorograph were then used to show that the epithelial cells do not have detectable receptors for the virus. However, implantation with Epstein-Barr virus receptors gave the cells the ability to bind the labeled virus. One to 5 percent of receptor-implanted cells exposed to the transforming B95-8 substrain of the virus expressed Epstein-Barr nuclear antigen. The early and viral capsid Epstein-Barr virus-determined antigens were not detected in the virus-infected cultures. The results show that normal human epithelial cells from the nasopharynx become susceptible to infection by Epstein-Barr virus when the membrane barrier resulting from the lack of viral receptors is overcome by receptor implantation.