EEG-Meta-Microstates: Towards a More Objective Use of Resting-State EEG Microstate Findings Across Studies.

Over the last decade, EEG resting-state microstate analysis has evolved from a niche existence to a widely used and well-accepted methodology. The rapidly increasing body of empirical findings started to yield overarching patterns of associations of biological and psychological states and traits with specific microstate classes. However, currently, this cross-referencing among apparently similar microstate classes of different studies is typically done by "eyeballing" of printed template maps by the individual authors, lacking a systematic procedure. To improve the reliability and validity of future findings, we present a tool to systematically collect the actual data of template maps from as many published studies as possible and present them in their entirety as a matrix of spatial similarity. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps from ongoing or published studies. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps in the literature. The analysis of 40 included sets of template maps indicated that: (i) there is a high degree of similarity of template maps across studies, (ii) similar template maps were associated with converging empirical findings, and (iii) representative meta-microstates can be extracted from the individual studies. We hope that this tool will be useful in coming to a more comprehensive, objective, and overarching representation of microstate findings.

Assessment of Acetabular Morphology Using the Acetabular Anterior Center-Edge Angle on Modified False-Profile Radiographs.

PURPOSE: To compare radiographic parameters of acetabular morphology between standard and modified false-profile (FP) radiographs. METHODS: Standard and modified FP radiographs were obtained in 225 hips in 200 consecutive patients evaluated for hip pain and suspected femoroacetabular impingement. Radiographs were retrospectively reviewed by 2 readers to determine the anterior center-edge angle (ACEA), as assessed to the sourcil and to the bone edge. Inter-rater reliability of radiographic measurements was assessed using the intraclass correlation coefficient. Measurements were evaluated for normality with the Shapiro-Wilk test, averaged between the 2 readers, and compared between views using the paired Wilcoxon test. RESULTS: The intraclass correlation coefficient values for standard and modified FP views were 0.923 and 0.932, respectively, measuring to the sourcil and 0.867 and 0.896, respectively, measuring to the lateral bone edge. The median difference in ACEA measurements to the sourcil was 1° between the standard and modified FP view (45° vs 44°, P < .001). The median difference in ACEA measurements to the bone edge was 2° (34° vs 32°, P < .001). CONCLUSIONS: Thirty-five degrees of femoral internal rotation for a modified FP hip radiographic view provides similar clinical information regarding acetabular morphology to that of the standard FP view. Given that the modified FP view also provides better visualization of the anterosuperior head-neck junction cam lesion, the modified FP view may be preferred over the standard FP view in evaluation of hip pain in the young patient. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

A Case Study of the Collapse of Slender Pillars Affected by Through-Going Discontinuities at a Limestone Mine in Pennsylvania.

The sudden collapse of approximately 3 Ha of room-and-pillar workings at a limestone mine in southwestern Pennsylvania in 2015 resulted in an air blast that injured three mine workers. Subsequent investigations showed that an area encompassing 35 pillars had collapsed. The pillars were 9-10 m wide and up to 18 m high. A notable geologic feature is the through-going joints that dip at 50-80° and can extend from the roof to the floor of the pillars. These structures are thought to have weakened the pillars well below the strength that is predicted by empirical equations for hard-rock pillar design. This paper presents the relevant geotechnical data related to the collapsed area and numerical model results that were used to estimate the pillar loading underneath the variable topography, and compares the pillar loads to some established hard-rock pillar strength equations. The outcome is also compared to a strength equation that was developed specifically for limestone mines in which the negative impact of large angular discontinuities is explicitly accounted for. The results show that established hard-rock pillar strength equations do not adequately account for the impact of large through-going discontinuities on the strength of slender pillars. The equations would have significantly overestimated the strength of the pillars at the case study mine. The critical state of the workings would have been predicted correctly by the limestone pillar strength equation that accounts for the large discontinuities.

Rotator Cuff Repair Technique With Transosseous Knotless Anchor System.

Various surgical techniques exist for rotator cuff repair that provide a suitable environment for tendon-bone healing. Arthroscopic recreation of transosseous repairs, which had previously been performed by open or miniopen techniques, can now be performed; however, arthroscopic, transosseous passage of suture material can be challenging technically. There are potential biologic and cost-saving advantages of arthroscopic transosseous rotator cuff repair that make an efficient and reproducible technique desirable for arthroscopists. The technique for arthroscopic transosseous rotator cuff repair using a knotless anchor-based system is demonstrated in the current Technical Note. Potential advantages of this construct include excellent biomechanics, enhanced footprint vascularization, and utility in poor bone quality while using minimal anchor numbers. Further studies will be needed to elucidate healing rates and clinical outcomes.

Analysis of the current rib support practices and techniques in U.S. coal mines.

Design of rib support systems in U.S. coal mines is based primarily on local practices and experience. A better understanding of current rib support practices in U.S. coal mines is crucial for developing a sound engineering rib support design tool. The objective of this paper is to analyze the current practices of rib control in U.S. coal mines. Twenty underground coal mines were studied representing various coal basins, coal seams, geology, loading conditions, and rib control strategies. The key findings are: (1) any rib design guideline or tool should take into account external rib support as well as internal bolting; (2) rib bolts on their own cannot contain rib spall, especially in soft ribs subjected to significant load-external rib control devices such as mesh are required in such cases to contain rib sloughing; (3) the majority of the studied mines follow the overburden depth and entry height thresholds recommended by the Program Information Bulletin 11-29 issued by the Mine Safety and Health Administration; (4) potential rib instability occurred when certain geological features prevailed-these include draw slate and/or bone coal near the rib/roof line, claystone partings, and soft coal bench overlain by rock strata; (5) 47% of the studied rib spall was classified as blocky-this could indicate a high potential of rib hazards; and (6) rib injury rates of the studied mines for the last three years emphasize the need for more rib control management for mines operating at overburden depths between 152.4 m and 304.8 m.

Anterior cruciate ligament reconstruction in skeletally immature patients.

The management of pediatric patients with an anterior cruciate ligament (ACL) tear can be a challenging endeavor for physicians, athletic trainers, coaches, and parents alike. In particular, the significant longitudinal growth that arises from the physes about the knee creates a unique set of circumstances that must be considered in this patient population. The purpose of this review is to provide a summary of the most recent current literature for the management of skeletally immature patients with an ACL tear.

Analysis of roof and pillar failure associated with weak floor at a limestone mine.

A limestone mine in Ohio has had instability problems that have led to massive roof falls extending to the surface. This study focuses on the role that weak, moisture-sensitive floor has in the instability issues. Previous NIOSH research related to this subject did not include analysis for weak floor or weak bands and recommended that when such issues arise they should be investigated further using a more advanced analysis. Therefore, to further investigate the observed instability occurring on a large scale at the Ohio mine, FLAC3D numerical models were employed to demonstrate the effect that a weak floor has on roof and pillar stability. This case study will provide important information to limestone mine operators regarding the impact of weak floor causing the potential for roof collapse, pillar failure, and subsequent subsidence of the ground surface.

A case study of multi-seam coal mine entry stability analysis with strength reduction method.

In this paper, the advantage of using numerical models with the strength reduction method (SRM) to evaluate entry stability in complex multiple-seam conditions is demonstrated. A coal mine under variable topography from the Central Appalachian region is used as a case study. At this mine, unexpected roof conditions were encountered during development below previously mined panels. Stress mapping and observation of ground conditions were used to quantify the success of entry support systems in three room-and-pillar panels. Numerical model analyses were initially conducted to estimate the stresses induced by the multiple-seam mining at the locations of the affected entries. The SRM was used to quantify the stability factor of the supported roof of the entries at selected locations. The SRM-calculated stability factors were compared with observations made during the site visits, and the results demonstrate that the SRM adequately identifies the unexpected roof conditions in this complex case. It is concluded that the SRM can be used to effectively evaluate the likely success of roof supports and the stability condition of entries in coal mines.

Osteochondral allograft transplant to the medial femoral condyle using a medial or lateral femoral condyle allograft: is there a difference in graft sources?

BACKGROUND: Osteochondral allograft (OCA) transplantation is an effective treatment for defects in the medial femoral condyle (MFC), but the procedure is limited by a shortage of grafts. Lateral femoral condyles (LFCs) differ in geometry from MFCs but may be a suitable graft source. The difference between articular surface locations of the knee can be evaluated with micro-computed tomography imaging and 3-dimensional image analysis. HYPOTHESIS: LFC OCAs inserted into MFC lesions can provide a cartilage surface match comparable with those provided by MFC allografts. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty MFCs and 10 LFCs were divided into 3 groups: 10 MFC recipients (MFCr), 10 MFC donors (MFCd), and 10 LFC donors (LFCd). A 20-mm defect was created in the weightbearing portion of the MFCr. Two grafts, 1 MFCd and 1 LFCd, were implanted sequentially into each MFCr. Micro-computed tomography (µCT) images of the MFCr were acquired and analyzed to compare the topography of the original recipient site with the MFCd- and LFCd-repaired sites. Three-dimensional transformations were defined to register the defect site in the 3 scans of each MFCr. Vertical deviations from each voxel of the graft cartilage surface, relative to the intact recipient cartilage surface, were calculated and assessed as root mean square deviation and percentage graft area that was proud, sunk, and within the "acceptable" distance (±1.00 mm). The effect of repair (with MFC vs with LFC) on each of the surface match parameters is presented as mean ± SD and was assessed by t test: height deviation over area (root mean square, mm), graft area acceptable (%), area unacceptably proud (%), area unacceptably sunk (%), step-off height over circumference (root mean square, mm), graft circumference acceptable (%), circumference unacceptably proud (%), and circumference unacceptably sunk (%). Percentage data were arcsin transformed before statistical testing. An alpha level of 0.05 was used to conclude if variations were statistically significant. RESULTS: MFCr defects were filled with both orthotopic MFCd and nonorthotopic LFCd. Registered µCT images of the MFCr illustrate the cartilage surface contour in the sagittal and coronal planes, in the original intact condyle, as well as after OCA repairs. Specimen-specific surface color maps for the MFCr after implant of the MFCd and after implant of LFCd were generally similar, with some deviation near the edges. On average, the MFCr site exhibited a typical contour, and the MFCd and LFCd were slightly elevated. Both types of OCA-MFCd and LFCd-matched well, showing overall height deviations of 0.63 mm for area and 0.47 mm for step-off, with no significant difference between MFCd and LFCd (P = .92 and .57, respectively) and acceptable deviation based on area (87.6% overall) and step-off (96.7% overall), with no significant difference between MFCd and LFCd (P = .87 and .22, respectively). A small portion of the implant was proud (12.1% of area and 2.6% of circumference step-off height), with no significant difference between MFCd and LFCd (P = .26 and .27, respectively). A very small portion of the implant area and edge was sunk (0.3% of area and 0.6% of circumference), with no significant difference between MFCd and LFCd (P = .29 and .86, respectively). CONCLUSION/CLINICAL RELEVANCE: The achievement of excellent OCA surface match with an MFCd or LFCd graft into the common MFCr site suggests that nonorthotopic LFC OCAs are acceptable graft options for MFC defects.

ATM-deficient thymic lymphoma is associated with aberrant tcrd rearrangement and gene amplification.

Ataxia telangiectasia mutated (ATM) deficiency predisposes humans and mice to T lineage lymphomas with recurrent chromosome 14 translocations involving the T cell receptor alpha/delta (Tcra/d) locus. Such translocations have been thought to result from aberrant repair of DNA double-strand breaks (DSBs) during Tcra locus V(D)J recombination, and to require the Tcra enhancer (Ealpha) for Tcra rearrangement or expression of the translocated oncogene. We now show that, in addition to the known chromosome 14 translocation, ATM-deficient mouse thymic lymphomas routinely contain a centromeric fragment of chromosome 14 that spans up to the 5' boundary of the Tcra/d locus, at which position a 500-kb or larger region centromeric to Tcra/d is routinely amplified. In addition, they routinely contain a large deletion of the telomeric end of one copy of chromosome 12. In contrast to prior expectations, the recurrent translocations and amplifications involve V(D)J recombination-initiated breaks in the Tcrd locus, as opposed to the Tcra locus, and arise independently of the Ealpha. Overall, our studies reveal previously unexpected mechanisms that contribute to the oncogenic transformation of ATM-deficient T lineage cells.

DNA-PKcs and Artemis function in the end-joining phase of immunoglobulin heavy chain class switch recombination.

The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Artemis are classical nonhomologous DNA end-joining (C-NHEJ) factors required for joining a subset of DNA double-strand breaks (DSB), particularly those requiring end processing. In mature B cells, activation-induced cytidine deaminase (AID) initiates class switch recombination (CSR) by introducing lesions into S regions upstream of two recombining C(H) exons, which are processed into DSBs and rejoined by C-NHEJ to complete CSR. The function of DNA-PKcs in CSR has been controversial with some reports but not others showing that DNA-PKcs-deficient mice are significantly impaired for CSR. Artemis-deficient B cells reportedly undergo CSR at normal levels. Overall, it is still not known whether there are any CSR-associated DSBs that require DNA-PKcs and/or Artemis to be joined. Here, we have used an immunoglobulin (Ig)H locus-specific fluorescent in situ hybridization assay to unequivocally demonstrate that both DNA-PKcs and, unexpectedly, Artemis are necessary for joining a subset of AID-dependent DSBs. In the absence of either factor, B cells activated for CSR frequently generate AID-dependent IgH locus chromosomal breaks and translocations. We also find that under specific activation conditions, DNA-PKcs(-/-) B cells with chromosomal breaks are eliminated or at least prevented from progressing to metaphase via a p53-dependent response.

B-cell receptor cross-linking delays activation-induced cytidine deaminase induction and inhibits class-switch recombination to IgE.

BACKGROUND: During differentiation, B cells receive signals by antigen through the B-cell receptor (BCR) and signals that induce isotype switching. OBJECTIVE: We sought to investigate the effects of BCR ligation on isotype switching. METHODS: Naive B cells from BALB/c mice were stimulated with LPS plus IL-4 alone or plus anti-IgM (0.1-10 mug/mL). IgE and IgG1 levels in supernatants were measured by means of ELISA on day 6. Cmu or Cvarepsilon germline transcripts, activation-induced cytidine deaminase (AID), and Imu-Cvarepsilon postswitch transcripts were measured by means of RT-PCR. Deletional switch recombination was assessed by means of digestion circularization PCR of Smu-Svarepsilon products. RESULTS: BCR cross-linking inhibited IgE and IgG1 switching in a dose-dependent fashion. This was not due to inhibition of proliferation, increased apoptosis, or cell death. BCR cross-linking had no effect on Cmu or Cvarepsilon germline transcripts but suppressed the generation of Smu-Svarepsilon switch products and Imu-Cvarepsilon postswitch transcripts and caused a delay in the expression of AID mRNA, with decreased expression on days 2 and 3 after stimulation. Concomitantly, the number of DNA repair foci at the IgH locus on day 3 was significantly decreased. AID expression and activity became normal on day 4, but isotype switching remained profoundly diminished 8 days after stimulation. CONCLUSION: BCR cross-linking delays AID expression. This might interfere with class-switch recombination by disrupting the temporal coordination of signals that lead to class-switch recombination.

ICOS-induced B7h shedding on B cells is inhibited by TLR7/8 and TLR9.

We report in this study that B7h, the ligand for the ICOS costimulatory receptor, is rapidly shed from mouse B cells following either ICOS binding or BCR engagement. Shedding occurs through proteolytic cleavage that releases the extracellular ICOS-binding region of B7h. Prior exposure of B7h-expressing APCs to ICOS-expressing cells inhibits their subsequent ability to costimulate IFN-gamma and IL-4 production from CD4+ T cells. Shedding is regulated as TLR7/8 and TLR9 ligands inhibit B7h shedding. A shedding-resistant B7h mutant elicits greater costimulation of IFN-gamma production from CD4+ T cells than does wild-type B7h. These data define shedding of B7h as a novel mechanism for controlling costimulatory signaling by B7-CD28 family members that is regulated on B cells by TLR signaling.

53BP1 and p53 synergize to suppress genomic instability and lymphomagenesis.

p53-binding protein 1 (53BP1) participates in the cellular response to DNA double-stranded breaks where it associates with various DNA repair/cell cycle factors including the H2AX histone variant. Mice deficient for 53BP1 (53BP1(-/-)) are sensitive to ionizing radiation and immunodeficient because of impaired Ig heavy chain class switch recombination. Here we show that, as compared with p53(-/-) mice, 53BP1(-/-)/p53(-/-) animals more rapidly develop tumors, including T cell lymphomas and, at lower frequency, B lineage lymphomas, sarcomas, and teratomas. In addition, T cells from animals deficient for both 53BP1 and p53 (53BP1(-/-)/p53(-/-)) display elevated levels of genomic instability relative to T cells deficient for either 53BP1 or p53 alone. In contrast to p53(-/-) T cell lymphomas, which routinely display aneuploidy but not translocations, 53BP1(-/-)/p53(-/-) thymic lymphomas fall into two distinct cytogenetic categories, with many harboring clonal translocations (40%) and the remainder showing aneuploidy (60%). We propose that 53BP1, in the context of p53 deficiency, suppresses T cell lymphomagenesis through its roles in both cell-cycle checkpoints and double-stranded break repair.

Genomic instability and aging-like phenotype in the absence of mammalian SIRT6.

The Sir2 histone deacetylase functions as a chromatin silencer to regulate recombination, genomic stability, and aging in budding yeast. Seven mammalian Sir2 homologs have been identified (SIRT1-SIRT7), and it has been speculated that some may have similar functions to Sir2. Here, we demonstrate that SIRT6 is a nuclear, chromatin-associated protein that promotes resistance to DNA damage and suppresses genomic instability in mouse cells, in association with a role in base excision repair (BER). SIRT6-deficient mice are small and at 2-3 weeks of age develop abnormalities that include profound lymphopenia, loss of subcutaneous fat, lordokyphosis, and severe metabolic defects, eventually dying at about 4 weeks. We conclude that one function of SIRT6 is to promote normal DNA repair, and that SIRT6 loss leads to abnormalities in mice that overlap with aging-associated degenerative processes.

H2AX prevents DNA breaks from progressing to chromosome breaks and translocations.

Histone H2AX promotes DNA double-strand break (DSB) repair and immunoglobulin heavy chain (IgH) class switch recombination (CSR) in B-lymphocytes. CSR requires activation-induced cytidine deaminase (AID) and involves joining of DSB intermediates by end joining. We find that AID-dependent IgH locus chromosome breaks occur at high frequency in primary H2AX-deficient B cells activated for CSR and that a substantial proportion of these breaks participate in chromosomal translocations. Moreover, activated B cells deficient for ATM, 53BP1, or MDC1, which interact with H2AX during the DSB response, show similarly increased IgH locus breaks and translocations. Thus, our findings implicate a general role for these factors in promoting end joining and thereby preventing DSBs from progressing into chromosomal breaks and translocations. As cellular p53 status does not markedly influence the frequency of such events, our results also have implications for how p53 and the DSB response machinery cooperate to suppress generation of lymphomas with oncogenic translocations.

Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress.

The Saccharomyces cerevisiae chromatin silencing factor Sir2 suppresses genomic instability and extends replicative life span. In contrast, we find that mouse embryonic fibroblasts (MEFs) deficient for SIRT1, a mammalian Sir2 homolog, have dramatically increased resistance to replicative senescence. Extended replicative life span of SIRT1-deficient MEFs correlates with enhanced proliferative capacity under conditions of chronic, sublethal oxidative stress. In this context, SIRT1-deficient cells fail to normally upregulate either the p19(ARF) senescence regulator or its downstream target p53. However, upon acute DNA damage or oncogene expression, SIRT1-deficient cells show normal p19(ARF) induction and cell cycle arrest. Together, our findings demonstrate an unexpected SIRT1 function in promoting replicative senescence in response to chronic cellular stress and implicate p19(ARF) as a downstream effector in this pathway.