Bilateral saccadic deficits following large and reversible inactivation of unilateral frontal eye field.

Inactivation permits direct assessment of the functional contribution of a given brain area to behavior. Previous inactivation studies of the frontal eye field (FEF) have either used large permanent ablations or reversible pharmacological techniques that only inactivate a small volume of tissue. Here we evaluated the impact of large, yet reversible, FEF inactivation on visually guided, delayed, and memory-guided saccades, using cryoloops implanted in the arcuate sulcus. While FEF inactivation produced the expected triad of contralateral saccadic deficits (increased reaction time, decreased accuracy and peak velocity) and performance errors (neglect or misdirected saccades), we also found consistent increases in reaction times of ipsiversive saccades in all three tasks. In addition, FEF inactivation did not increase the proportion of premature saccades to ipsilateral targets, as was predicted on the basis of pharmacological studies. Consistent with previous studies, greater deficits accompanied saccades toward extinguished visual cues. Our results attest to the functional contribution of the FEF to saccades in both directions. We speculate that the comparative effects of different inactivation techniques relate to the volume of inactivated tissue within the FEF. Larger inactivation volumes may reveal the functional contribution of more sparsely distributed neurons within the FEF, such as those related to ipsiversive saccades. Furthermore, while focal FEF inactivation may disinhibit the mirroring site in the other FEF, larger inactivation volumes may induce broad disinhibition in the other FEF that paradoxically prolongs oculomotor processing via increased competitive interactions

Resource Adequacy: Should Regulators Worry?

Regulators have proposed various institutional alternatives to secure network resource adequacy and reasonably priced electric power for consumers. These alternatives prompt many difficult questions: Does the development of Demand Response reduce the need for new capacity? How effectively can a government-mandated Capacity Market foster efficient investment? How does centralized generator commitment (with revenue guarantees) compare to a system in which Generators voluntarily commit themselves with no revenue guarantees? If exclusive distribution contracts were replaced by unregulated retail competition, what would be the effects on investment and market prices? We use laboratory experiments to address these questions

Household Clustering of Escherichia coli Sequence Type 131 Clinical and Fecal Isolates According to Whole Genome Sequence Analysis

Background. Within-household sharing of strains from the resistance-associated H30R1 and H30Rx subclones of Escherichia coli sequence type 131 (ST131) has been inferred based on conventional typing data, but has been assessed minimally using whole genome sequence (WGS) analysis. Methods. Thirty-three clinical and fecal isolates of ST131-H30R1 and ST131-H30Rx, from 20 humans and pets in six households, underwent WGS analysis for comparison with 52 published ST131 genomes. Phylogenetic relationships were inferred using a bootstrapped maximum likelihood tree based on core genome sequence polymorphisms. Accessory traits were compared between phylogenetically similar isolates. Results. In the WGS-based phylogeny, isolates clustered strictly by household, in clades that were distributed widely across the phylogeny, interspersed between H30R1 and H30Rx comparison genomes. For only one household did the core genome phylogeny place epidemiologically unlinked isolates together with household isolates, but even there multiple differences in accessory genome content clearly differentiated these two groups. The core genome phylogeny supported within-household strain sharing, fecal-urethral urinary tract infection pathogenesis (with the entire household potentially providing the fecal reservoir), and instances of host-specific microevolution. In one instance the household\u27s index strain persisted for 6 years before causing a new infection in a different household member. Conclusions. Within-household sharing of E. coli ST131 strains was confirmed extensively at the genome level, as was long-term colonization and repeated infections due to an ST131-H30Rx strain. Future efforts toward surveillance and decolonization may need to address not just the affected patient but also other human and animal household members

Cross-cultural effects of color, but not morphological masculinity, on perceived attractiveness of men's faces

This is the post-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2012 ElsevierMuch attractiveness research has focused on face shape. The role of masculinity (which for adults is thought to be a relatively stable shape cue to developmental testosterone levels) in male facial attractiveness has been examined, with mixed results. Recent work on the perception of skin color (a more variable cue to current health status) indicates that increased skin redness, yellowness, and lightness enhance apparent health. It has been suggested that stable cues such as masculinity may be less important to attractiveness judgments than short-term, more variable health cues. We examined associations between male facial attractiveness, masculinity, and skin color in African and Caucasian populations. Masculinity was not found to be associated with attractiveness in either ethnic group. However, skin color was found to be an important predictor of attractiveness judgments, particularly for own-ethnicity faces. Our results suggest that more plastic health cues, such as skin color, are more important than developmental cues such as masculinity. Further, unfamiliarity with natural skin color variation in other ethnic groups may limit observers' ability to utilize these color cues

A randomized phase II study of lapatinib + pazopanib versus lapatinib in patients with HER2+ inflammatory breast cancer

This multi-center Phase II study evaluated lapatinib, pazopanib, and the combination in patients with relapsed HER2+ inflammatory breast cancer. In Cohort 1, 76 patients were randomized 1:1 to receive lapatinib 1,500 mg + placebo or lapatinib 1,500 mg + pazopanib 800 mg (double-blind) once daily until disease progression, unacceptable toxicity, or death. Due to high-grade diarrhea observed with this dose combination in another study (VEG20007), Cohort 1 was closed. The protocol was amended such that an additional 88 patients (Cohort 2) were randomized in a 5:5:2 ratio to receive daily monotherapy lapatinib 1,500 mg, lapatinib 1,000 mg + pazopanib 400 mg, or monotherapy pazopanib 800 mg, respectively. The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response, progression-free survival (PFS), overall survival, and safety. In Cohort 1, ORR for the lapatinib (n = 38) and combination (n = 38) arms was 29 and 45 %, respectively; median PFS was 16.1 and 14.3 weeks, respectively. Grade ≥3 adverse events (AEs) were more frequent in the combination arm (71 %) than in the lapatinib arm (24 %). Dose reductions and interruptions due to AEs were also more frequent in the combination arm (45 and 53 %, respectively) than in the lapatinib monotherapy arm (0 and 11 %, respectively). In Cohort 2, ORR for patients treated with lapatinib (n = 36), lapatinib + pazopanib (n = 38), and pazopanib (n = 13) was 47, 58, and 31 %, respectively; median PFS was 16.0, 16.0, and 11.4 weeks, respectively. In the lapatinib, combination, and pazopanib therapy arms, grade ≥3 AEs were reported for 17, 50, and 46 % of patients, respectively, and the incidence of discontinuations due to AEs was 0, 24, and 23 %, respectively. The lapatinib–pazopanib combination was associated with a numerically higher ORR but no increase in PFS compared to lapatinib alone. The combination also had increased toxicity resulting in more dose reductions, modifications, and treatment delays. Activity with single-agent lapatinib was confirmed in this population

Ultrasonographic assessment of the male koala (Phascolarctos cinereus) reproductive tract

Studies documenting the application of ultrasonography to depict normal and pathological changes in koalas (Phascolarctos cinereus), especially in the male, are scarce. Sixty-two wild koalas were used in this study to define ultrasonographic protocols and features for the assessment of the male koala reproductive tract. Testis, epididymis and spermatic cord were examined using a hockey stick transducer. The normal koala testis showed a homogeneous echogenicity and an obvious hyper-echoic band corresponding to the tunica albuginea. The cauda epididymis was characterised by hypo- and hyper-echoic regions and was most effectively imaged in sagittal section. The koala prostate was assessed using a micro-curved transducer positioned midline, caudal to the bladder. On transverse section, it showed distinct margins and a well-defined internal structure, although the prostatic urethra was not apparent on most scans. To image the bulbourethral glands (BGs), the hockey stick transducer was placed lateral to the cloaca. BGIII was located just below the skin, while BGII was located deeper than BGIII. BGI was too small and not sufficiently echogenic to be detected. The ultrasonographic appearance of the BGs was similar to that of the testes but with more obvious hypo-echoic stippling. This comprehensive review of the ultrasonographic appearance of normal male koala reproductive tract can be used by veterinarians and others, in zoos or those working with wild koalas, during assessment of the reproductive tract of male koalas in relation to seasonal changes in accessory gland function or for the pathological investigation of reproductive lesions and infertility problems

Cumulus Cell DNA damage as an index of human oocyte competence

The determination of oocyte quality is crucial for achieving effective syngamy post-sperm injection and embryonic development. Cumulus cells (CCs) have been proposed as biomarkers of oocyte quality because of their close bio-dynamic relationship with the oocyte. To determine the quality of the oocyte, CCs were sampled during oocyte preparation for ICSI to determine a CC DNA fragmentation index (CCDFI) of each individual oocyte using a variant of the chromatin dispersion test. One hundred and thirty oocytes were selected and studied from two Spanish fertility clinics, 90 of which were fertilized and developed to embryos. Significant differences were found between the CCDFI of unfertilized and fertilized oocytes (p <.001) and between the CCDFI of embryos that were discarded and those that developed suitable for transfer or cryopreservation (p <.001). Oocyte quality was negatively correlated with CCDFI (Spearman’s rho = − 0.45; p <.001). Receiver operator characteristics curves (ROC) suggested that a cut-off value of 24% CCDFI was able to discriminate the capacity of the gametes to result in syngamy with a sensitivity and specificity of 75.6% and 65%, respectively. This cut-off supports the application of CCDFI as potential index for the evaluation of the reproductive potential of oocytes prior to fertilizatio

Molecular epidemiology of Escherichia coli sequence type 131 and its H30 and H30-Rx subclones among extended-spectrum-β-lactamase-positive and -negative E. coli clinical isolates from the Chicago region, 2007 to 2010

We assessed Escherichia coli ST131 and its H30 and H30-Rx subclones for virulence genes, antimicrobial resistance, and extended-spectrum beta-lactamase (ESBL) type. Although both subclones were associated with ESBL production, H30-Rx isolates had higher resistance scores and were associated specifically with CTX-M-15. Three virulence genes (iha, sat, and iutA) were more prevalent among H30 than non-H30 ST131 isolates. Thus, the H30 and H30-Rx subclones are more antimicrobial resistant and have virulence profiles that are distinct from those of non-H30 ST131 isolates