Vertebral deformities and fractures are associated with MRI and pQCT measures obtained at the distal tibia and radius of postmenopausal women.

SUMMARY: We investigated the association of postmenopausal vertebral deformities and fractures with bone parameters derived from distal extremities using MRI and pQCT. Distal extremity measures showed variable degrees of association with vertebral deformities and fractures, highlighting the systemic nature of postmenopausal bone loss. INTRODUCTION: Prevalent vertebral deformities and fractures are known to predict incident further fractures. However, the association of distal extremity measures and vertebral deformities in postmenopausal women has not been fully established. METHODS: This study involved 98 postmenopausal women (age range 60-88 years, mean 70 years) with DXA BMD T-scores at either the hip or spine in the range of -1.5 to -3.5. Wedge, biconcavity, and crush deformities were computed on the basis of spine MRI. Vertebral fractures were assessed using Eastell's criterion. Distal tibia and radius stiffness was computed using MRI-based finite element analysis. BMD at the distal extremities were obtained using pQCT. RESULTS: Several distal extremity MRI and pQCT measures showed negative association with vertebral deformity on the basis of single parameter correlation (r up to 0.67) and two-parameter regression (r up to 0.76) models involving MRI stiffness and pQCT BMD. Subjects who had at least one prevalent vertebral fracture showed decreased MRI stiffness (up to 17.9 %) and pQCT density (up to 34.2 %) at the distal extremities compared to the non-fracture group. DXA lumbar spine BMD T-score was not associated with vertebral deformities. CONCLUSIONS: The association between vertebral deformities and distal extremity measures supports the notion of postmenopausal osteoporosis as a systemic phenomenon.

Gaze onsets during naturalistic infant-caregiver interaction associate with 'sender' but not 'receiver' neural responses, and do not lead to changes in inter-brain synchrony.

Temporal coordination during infant-caregiver social interaction is thought to be crucial for supporting early language acquisition and cognitive development. Despite a growing prevalence of theories suggesting that increased inter-brain synchrony associates with many key aspects of social interactions such as mutual gaze, little is known about how this arises during development. Here, we investigated the role of mutual gaze onsets as a potential driver of inter-brain synchrony. We extracted dual EEG activity around naturally occurring gaze onsets during infant-caregiver social interactions in N = 55 dyads (mean age 12 months). We differentiated between two types of gaze onset, depending on each partners' role. 'Sender' gaze onsets were defined at a time when either the adult or the infant made a gaze shift towards their partner at a time when their partner was either already looking at them (mutual) or not looking at them (non-mutual). 'Receiver' gaze onsets were defined at a time when their partner made a gaze shift towards them at a time when either the adult or the infant was already looking at their partner (mutual) or not (non-mutual). Contrary to our hypothesis we found that, during a naturalistic interaction, both mutual and non-mutual gaze onsets were associated with changes in the sender, but not the receiver's brain activity and were not associated with increases in inter-brain synchrony above baseline. Further, we found that mutual, compared to non-mutual gaze onsets were not associated with increased inter brain synchrony. Overall, our results suggest that the effects of mutual gaze are strongest at the intra-brain level, in the 'sender' but not the 'receiver' of the mutual gaze.

Measuring the temporal dynamics of inter-personal neural entrainment in continuous child-adult EEG hyperscanning data.

Current approaches to analysing EEG hyperscanning data in the developmental literature typically consider interpersonal entrainment between interacting physiological systems as a time-invariant property. This approach obscures crucial information about how entrainment between interacting systems is established and maintained over time. Here, we describe methods, and present computational algorithms, that will allow researchers to address this gap in the literature. We focus on how two different approaches to measuring entrainment, namely concurrent (e.g., power correlations, phase locking) and sequential (e.g., Granger causality) measures, can be applied to three aspects of the brain signal: amplitude, power, and phase. We guide the reader through worked examples using simulated data on how to leverage these methods to measure changes in interbrain entrainment. For each, we aim to provide a detailed explanation of the interpretation and application of these analyses when studying neural entrainment during early social interactions.

Strategies for optical control and simultaneous electrical readout of extended cortical circuits.

BACKGROUND: To dissect the intricate workings of neural circuits, it is essential to gain precise control over subsets of neurons while retaining the ability to monitor larger-scale circuit dynamics. This requires the ability to both evoke and record neural activity simultaneously with high spatial and temporal resolution. NEW METHOD: In this paper we present approaches that address this need by combining micro-electrocorticography (µECoG) with optogenetics in ways that avoid photovoltaic artifacts. RESULTS: We demonstrate that variations of this approach are broadly applicable across three commonly studied mammalian species - mouse, rat, and macaque monkey - and that the recorded µECoG signal shows complex spectral and spatio-temporal patterns in response to optical stimulation. COMPARISON WITH EXISTING METHODS: While optogenetics provides the ability to excite or inhibit neural subpopulations in a targeted fashion, large-scale recording of resulting neural activity remains challenging. Recent advances in optical physiology, such as genetically encoded Ca(2+) indicators, are promising but currently do not allow simultaneous recordings from extended cortical areas due to limitations in optical imaging hardware. CONCLUSIONS: We demonstrate techniques for the large-scale simultaneous interrogation of cortical circuits in three commonly used mammalian species.

Effects of unopposed conjugated equine estrogen on lipoprotein composition and apolipoprotein-E distribution.

Administration of conjugated equine estrogen to 31 postmenopausal women for 3 months produced 14.6% and 9.4% decreases in low density lipoprotein cholesterol (LDL-C) and apolipoprotein-B (apoB), and 11.5%, 12.7%, and 9.6% increases in high density lipoprotein cholesterol (HDL-C), apoA-I and apoA-II, respectively. Phospholipids of HDL2 and HDL3 were increased 57.9% and 19.3%, respectively, while relatively small increases in cholesterol of the two subfractions were not significant. Compositions of LDL and HDL and its subfractions were altered substantially with estrogen treatment. The proportion of LDL triglyceride to LDL-C was increased. The phospholipid content in both the HDL2 and HDL3 subfractions (compared to cholesterol) was increased significantly (34.8% and 10.7%, respectively), while the triglyceride content was increased only in the HDL2 subfraction (43.6%). Estrogen use also caused a 9.1% reduction in total apoE levels and a redistribution of apoE to the very low density lipoprotein (VLDL) from the LDL plus HDL fraction, resulting in a significant 19.5% decrease in apoE in the LDL plus HDL fraction. Changes in apoE in the VLDL fraction were associated positively with changes in the cholesterol levels of the VLDL fraction and inversely with changes in LDL-C and apoB levels, while changes in apoE in the LDL plus HDL fraction were associated positively with changes in the levels of HDL-C. Thus, estrogen causes alterations in lipoproteins that could potentially affect their metabolism and/or function.

Statistical methods for studying homozygous typing cells of unknown specificity.

A situation can arise in D typing in which the HLA (A,B,C,D, or DR) specificities of the responders are known and the specificities of the HTC's are unknown. The most powerful and direct method of detecting association between the unknown stimulator (HTC) and any given HLA specificity is by comparing the observed double normalized values (DNV's) of individuals known to be positive for the specificity with the DNV's of negative individuals. This can be done by comparing the two groups with a Kolmogorov-Smirnov test (K-S test), an established statistical procedure for evaluating correlation between continuous variables, such as the DNV, and discrete variables (such as presence of D type). The application of the K-S test will generate as a "cutoff" value of point that maximizes the average of the frequencies of correct assignments in D positives and D negatives. We also propose an alternative method of computing the "r" value. We have analyzed 49 HTC's from the 8th International Workshop and present the association observed with the D and DR specificities.

Effects of conjugated equine estrogen with and without three different progestogens on lipoproteins, high-density lipoprotein subfractions, and apolipoprotein A-I.

The effects of conjugated equine estrogen and subsequent cyclical progestogen supplementation on lipoprotein and apolipoprotein A-I levels were investigated in three groups of postmenopausal women. Unopposed conjugated equine estrogen (0.625 mg) lowered total cholesterol 4-8% and low-density lipoprotein (LDL) cholesterol 12-19% below pre-treatment levels in all three groups. Levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I were increased 9-13 and 9-18%, respectively, with unopposed estrogen. The increase in HDL cholesterol was mainly due to increases in the high-density lipoprotein2 (HDL2) subfraction. Addition of medroxyprogesterone acetate, norethindrone acetate, or d,l-norgestrel at doses shown previously to provide protection against endometrial hyperplasia reversed some of the beneficial estrogen effects, reducing levels of HDL cholesterol 14-17%, HDL2 cholesterol 22-37%, and apolipoprotein A-I 11-15% from those obtained with unopposed estrogen. The LDL cholesterol levels fell 12-19% with unopposed estrogen but remained 7-12% below baseline when progestogens were added. These observations demonstrate that after 3 months of treatment, all three progestogens reversed some of the favorable effects of unopposed estrogen on lipoproteins but permitted a continued modest reduction in LDL cholesterol.

Presumptive identification of group B streptococci by rapid detection of CAMP factor and pigment production.

Modified rapid versions of CAMP and pigment tests were developed for the identification of group B streptococci using the supernatant and cell deposit of organisms grown for 4 hr in a modified Todd-Hewitt broth. All but one of 203 group B streptococci were reliably differentiated from 148 nongroup B strains.

A cellulose acetate membrane precipitin (CAP) test for amoebiasis.

A simple precipitin test (CAP) using cellulose acetate membrane has been devised and evaluated against the gel diffusion precipitin (GDP) test. In 251 sera tested by both methods, the CAP was never negative when the GDP was positive (110 sera). 34 sera were negative by the GDP but positive by the CAP; in all of these the patients either had a past history of amoebiasis or were considered to have active amoebiasis. The CAP is technically very simple, the result is available within four and a half hours, and the membranes can be impregnated with antigen and stored for several months. The CAP is slightly more sensitive than the GDP and remains positive longer after the patient has been cured; it seems to be equally specific.

The sensitivity of 173 Sydney isolates of Neisseria gonorrhoeae to cefpodoxime and other antibiotics used to treat gonorrhea.

One hundred and thirty seven consecutive isolates of Neisseria gonorrhoeae and a further 36 selected gonococci with either chromosomal (CMRNG) or plasmid mediated (PPNG) resistance to penicillin, all cultured in Sydney in 1993, were found to be sensitive to cefpodoxime, an oral third generation cephalosporin antibiotic (MIC range < 0.001-0.25 mg/L). All isolates were also sensitive to ceftriaxone and spectinomycin. Six gonococci showed high level resistance to tetracycline (TRNG, MIC = 32 mg/L) and 12 had decreased susceptibility to quinolone antibiotics (MIC range 0.06-0.5 mg/L). The MIC50 and MIC90 for both cefpodoxime and ceftriaxone were highest amongst CMRNG and ceftriaxone was 2 to 4 times as active as cefpodoxime weight for weight. Cefpodoxime may be a valuable additional oral agent for the treatment of gonorrhea in Australia. The sensitivity of gonococci to cefpodoxime can probably be inferred from values obtained for ceftriaxone.

The influence of nutritional and cultural factors on CAMP factor production by group B streptococci.

Twelve group B streptococci were examined for their capacity to produce CAMP factor in liquid culture media in which the carbohydrate type and concentration and/or the buffering capacity of the media were altered. The effects of these variations of media content on CAMP factor production were determined and related to effects on growth yield and pH changes during growth. For 9 of the 12 strains tested higher CAMP factor titres were obtained in maltose broth than in glucose broth, and accompanying changes in pH were greater and more rapid in glucose containing media. It is suggested that the lesser pH changes occurring during growth in maltose broth may be the mechanism whereby higher CAMP titres were obtained with these strains. The influence of carbohydrate type was not observed with the remaining 3 strains tested, but maximum CAMP factor yields were obtained in the presence of maltose and non-inhibitory concentrations of buffer. CAMP factor production for all strains of GBS may be increased by the addition of maltose and buffer to standard media.

The hemolytic and cytolytic activity of group B streptococcal hemolysin and its possible role in early onset group B streptococcal disease.

The in vitro and cytolytic properties of the hemolysin of group B streptococcus (GBS) were investigated using sheep erythrocytes and McCoy cells adapted for growth in a serum-deficient medium. The relationship between the hemolysin, various carrier molecules and phospholipids was examined. Starch-based carriers interfered with the inhibitory activity of phospholipids and solvents for the phospholipids reduced the activity of the hemolysin. These technical problems were resolved by use of an albumin-based carrier, a strain producing large amounts of hemolysin and sonication of the phospholipid. The hemolysin was cytolytic for McCoy cells and this activity and its hemolytic action on sheep erythrocytes were inhibited by a number of phospholipid components of surfactant. It is possible that GBS hemolysin has a direct or indirect role in the pathogenesis of the pneumonitis of early onset GBS infection.

Characteristics of Neisseria gonorrhoeae isolated in Australia showing decreased sensitivity to quinolone antibiotics.

Forty three strains of Neisseria gonorrhoeae with decreased sensitivity to quinolone antibiotics were detected amongst 2141 Australian isolates of gonococci examined in the years 1984 to 1990. The strains examined belonged to 23 different auxotype/serovar classes, were generally more resistant to other antibiotics and, in the majority of cases, were isolated from travellers entering or returning to Australia from SE Asia. Quinolone-sensitive wild-type gonococci became less sensitive to these agents in vitro at a relatively high frequency when grown in the presence of quinolone concentrations at or around the MIC (Mean Inhibitory Concentration) of the antibiotic. Further increments in the levels of quinolone resistance of the already less-sensitive gonococci were also produced by this means, but high-level resistance to these agents was not observed. This suggests that mechanisms other than alterations in the DNA-gyrase of the organisms were responsible for the changes seen. Although spread of quinolone resistance in gonococci in Australia is unlikely to be rapid, if these antibiotics are used in therapy, treatment regimens with higher rather than lower dosages of quinolone antibiotics should be employed.

Strain characteristics and antibiotic susceptibility of isolates of Neisseria gonorrhoeae causing disseminated gonococcal infection in Australia. Members of the Australian Gonococcal Surveillance Programme.

The auxotype (A) and serovar (S) distribution and antibiotic and serum sensitivity of 22 strains of Neisseria gonorrhoeae isolated from blood and joints were determined. With one exception, these strains from disseminated gonococcal infections (DGI) belonged to one of 4 serovars of the IA serogroup and were resistant to killing by normal human serum. The auxotype distribution of these Australian strains differed significantly from that reported elsewhere in that 17 of the 22 isolates were proline requires, but none were of the AHU auxotype. This lack of the AHU auxotype in the DGI strains in Australia was explained by the virtual absence of AHU requirers in a sample of 1560 mucosal strains isolated in Sydney and Darwin from 1987 to 1990. The A/S distribution of these mucosal isolates also helped to account for the low (0.12) percentage of DGI strains in isolates examined by the Australian Gonococcal Surveillance Programme (AGSP) from 1981 to 1991, and the differences in the rates of DGI in Sydney (0.08%) and Darwin (0.87%). There was a relative lack of the IA serogroup strains which are mostly responsible for DGI in the mucosal isolates from Sydney (15% of all strains) but a higher proportion of these serovars (40%) in the Darwin sample. There were 46 cases of DGI in data from the AGSP, 29 of these being women. Seven of the cases diagnosed in Australia were infected with penicillinase-producing gonococci suggesting that antibiotics other than the penicillins should now be used for this condition in this region.

Achievement Place: development of the elected manager system.

A series of experiments was carried out to compare several administrative systems at Achievement Place, a family style behavior modification program for pre-delinquent boys. One aspect of the motivation system at Achievement Place was the token economy in which the youths could earn or lose points that could be exchanged for privileges. Several arrangements for assigning routine tasks and for providing token consequences for task performance were compared for their effectiveness in accomplishing the tasks and for their preference by the boys. The independent variables studied included: (1) individually assigned tasks versus group assigned tasks; (2) consequences for individual performance versus consequences for group performance; (3) a peer managership that could be earned by the highest bidder versus a peer managership that could be determined democratically by the peers. The results suggested that among those systems studied the system that best met the criteria of effectiveness and preference involved a democratically elected peer manager who had the authority both to give and to take away points for his peers' performances.

Achievement Place: modification of the behaviors of pre-delinquent boys within a token economy.

The "pre-delinquent" behaviors of six boys at Achievement Place, a community based family style behavior modification center for delinquents, were modified using token (points) reinforcement procedures. In Exp. I, point losses contingent on each minute late were effective in producing promptness at the evening meal. During the reversal phase, threats (which were not backed up with point losses) to reinstate the point consequences initially improved promptness but the last two of five threats were ineffective. In Exp. II, point consequences effectively maintained the boys' room-cleaning behavior and, during a fading condition where the percentage of days when the contingency occurred was decreased, the point consequences remained effective for over six months, even when they were delivered on only 8% of the days. Experiment III showed that the boys saved considerable amounts of money when point consequences were available for deposits but saved little money when no points were available. Also, when points were given only for deposits that occurred on specific days the boys deposited their money almost exclusively on those days. In Exp. IV, point consequences contingent on the number of correct answers on a news quiz produced the greatest increase in the percentage of boys who watched the news and, to a lesser extent, increased the percentage of correct answers for the boys who watched the news. The results indicate that "pre-delinquent" behaviors are amenable to modification procedures and that a token reinforcement system provides a practical means of modifying these behaviors.

A survey of sexually transmitted diseases in five STD clinics in Papua New Guinea.

The first multicentre survey of sexually transmitted diseases (STDs) performed in Papua New Guinea was conducted in STD clinics in five towns, Port Moresby, Goroka, Rabaul, Lae and Daru, from September 1989 to May 1990. Infections with Neisseria gonorrhoeae and Chlamydia trachomatis (alone or in combination) were common. Penicillinase-producing N. gonorrhoeae (PPNG) represented 44% of all gonococcal isolates but significant intrinsic resistance to penicillin was not found. Of the other antibiotics tested, significant elevation of minimum inhibitory concentration (MIC) was common only for tetracycline, although no high-level tetracycline resistance was detected. C. trachomatis was detected by direct immunofluorescence (DIF) in 26% of 210 males and 27% of 64 females. 10% (21/210) of males and 11% (7/64) of females were both DIF positive for C. trachomatis and culture positive for N. gonorrhoeae. Of 203 males and 78 females tested, 5% and 12%, respectively, had serological evidence of current syphilis infection. Clinically, genital ulcer disease was most commonly due to syphilis, donovanosis or genital herpes, while specific vaginal infections were commonly seen in female patients attending Port Moresby and Lae STD clinics.

Experimental limits on weak annihilation contributions to decays.

We present the first experimental limits on high-q2 contributions to charmless semileptonic decays of the form expected from the weak annihilation (WA) decay mechanism. Such contributions could bias determinations of /Vub/ from inclusive measurements of B-->Xulupsilon. Using a wide range of models based on available theoretical input we set a limit of GammaWA/Gammab-->u<7.4% (90% confidence level) on the WA fraction, and assess the impact on previous inclusive determinations of /Vub/.

Observation of psi(3770) --> pi pi J/psi and measurement of Gamma ee[psi(2S)].

We observe signals for the decays psi(3770) --> XJ/psi from data acquired with the CLEO detector operating at the CESR e+ e- collider with square root of s = 3773 MeV. We measure the following branching fractions Beta(psi(3770) --> XJ/psi and significances: (189 +/- 20 +/- 20) x 10(-5) (11.6sigma) for X = pi+ pi-, (80 +/- 25 +/- 16) x 10(-5) (3.4sigma) for X = pi0 pi0, and (87 +/- 33 +/- 22) x 10(-5) (3.5sigma) for X = eta, where the errors are statistical and systematic, respectively. The radiative return process e+ e- --> gamma psi(2S) populates the same event sample and is used to measure Gamma ee[psi(2S)] = (2.54 +/- 0.03 +/- 0.11) keV.

Dielectron widths of the Gamma(1S,2S,3S) resonances.

We determine the dielectron widths of the Gamma(1S), Gamma(2S), and Gamma(3S) resonances with better than 2% precision by integrating the cross section of e+e- -->Gamma over the e+e- center-of-mass energy. Using e+e- energy scans of the Gamma resonances at the Cornell Electron Storage Ring and measuring Gamma production with the CLEO detector, we find dielectron widths of 1.252+/-0.004(sigma(stat))+/-0.019(sigma(syst)) keV, 0.581+/-0.004+/-0.009 keV, and 0.413+/-0.004+/-0.006 keV for the Gamma(1S), Gamma(2S), and Gamma(3S), respectively.