Multiple Images of a Highly Magnified Supernova Formed by an Early-Type Cluster Galaxy Lens

In 1964, Refsdal hypothesized that a supernova whose light traversed multiple paths around a strong gravitational lens could be used to measure the rate of cosmic expansion. We report the discovery of such a system. In Hubble Space Telescope imaging, we have found four images of a single supernova forming an Einstein cross configuration around a redshift z=0.54 elliptical galaxy in the MACS J1149.6+2223 cluster. The cluster's gravitational potential also creates multiple images of the z=1.49 spiral supernova host galaxy, and a future appearance of the supernova elsewhere in the cluster field is expected. The magnifications and staggered arrivals of the supernova images probe the cosmic expansion rate, as well as the distribution of matter in the galaxy and cluster lenses.Comment: Published in the 6 March 2015 issue of Science; 17 pages, 7 figures, and 3 tables including Supplementary Material

Propagation of Epileptiform Events across the Corpus Callosum in a Cingulate Cortical Slice Preparation

We report on a novel mouse in vitro brain slice preparation that contains intact callosal axons connecting anterior cingulate cortices (ACC). Callosal connections are demonstrated by the ability to regularly record epileptiform events between hemispheres (bilateral events). That the correlation of these events depends on the callosum is demonstrated by the bisection of the callosum in vitro. Epileptiform events are evoked with four different methods: (1) bath application of bicuculline (a GABA-A antagonist); (2) bicuculline+MK801 (an NMDA receptor antagonist), (3) a zero magnesium extracellular solution (0Mg); (4) focal application of bicuculline to a single cortical hemisphere. Significant increases in the number of epileptiform events, as well as increases in the ratio of bilateral events to unilateral events, are observed during bath applications of bicuculline, but not during applications of bicuculline+MK-801. Long ictal-like events (defined as events >20 seconds) are only observed in 0Mg. Whole cell patch clamp recordings of single neurons reveal strong feedforward inhibition during focal epileptiform events in the contralateral hemisphere. Within the ACC, we find differences between the rostral areas of ACC vs. caudal ACC in terms of connectivity between hemispheres, with the caudal regions demonstrating shorter interhemispheric latencies. The morphologies of many patch clamped neurons show callosally-spanning axons, again demonstrating intact callosal circuits in this in vitro preparation

Elbow Common Flexor Tendon Repair Technique

Medial epicondylitis, also known as “golfer's elbow,” is a common orthopaedic condition that typically results from overuse of the flexor pronator mass. Repetitive eccentric loading of the muscles responsible for wrist flexion and forearm pronation leads to microtrauma and subsequent degeneration of the flexor pronator tendon. Patients with medial epicondylitis typically present in the fourth to sixth decade of life and have an insidious onset of medial elbow pain. Occasionally, medial epicondylitis may result from an acute traumatic event, such as an acute avulsion of the common flexor tendon. Patients should be examined for concomitant elbow pathologies, including ulnar neuritis and ulnar collateral ligament injury. T2-weighted magnetic resonance imaging can show increased signal intensity in the common flexor tendon or a complete rupture. Nonsurgical management is the mainstay of treatment; however, surgical treatment may be indicated in elite athletes and patients with persistent symptoms after conservative treatment. This technique article with accompanying video describes open debridement and repair of the flexor pronator tendon, with an emphasis on restoration of the anatomic footprint and compression across the repair site to promote biological healing

Distal Knee Medial Collateral Ligament Repair With Suture Augmentation

The medial collateral ligament (MCL) is the most commonly injured ligament of the knee. Given its extra-articular location, the MCL has great healing capacity such that the mainstay of treatment for most injuries remains conservative management. However, certain injury patterns place patients and athletes at risk of residual valgus laxity, which may require delayed surgical care and prolonged time out from sports. As such, identifying the specific injuries known to place patients at risk for failure with nonoperative management is of paramount importance. Although controversy remains regarding the optimal treatment of grade III MCL injuries, it is generally accepted that MCL ruptures from the distal tibia attachment require operative fixation. This technique article with accompanying video provides a detailed description of a technique for repairing the distal MCL attachment with suture augmentation. There are several advantages associated with an augmented direct repair including early, safe rehabilitation; prevention of valgus instability; and avoiding the comorbidities associated with a larger reconstruction

Comparison of epileptiform events (EEs).

<p>BIC and 0Mg models are compared. The numbers represent the mean ± SE (n) for each measurement. For all means, only slices with greater than 10 EEs are included (22 out of 27 slices for 0Mg, 17/17 slices for BIC). For the BIC IHL measurements and Proportion of Unilateral EEs, only slices 3 and 4 are included, as no slice 2 was measured in 0Mg.</p>a<p>p<0.01, 0Mg greater than BIC (rank sum test).</p>b<p>p<0.01, 0Mg less than BIC (rank sum test).</p>c<p>p<0.04, 0Mg greater than BIC (rank sum test).</p

Injection of bicuculline in one hemisphere results in bursts of IPSCs in the contralateral hemisphere.

<p>(<b>A</b>) Fifteen minutes of a representative recording of IPSCs (blue trace) and EEs (black trace) are shown (same format as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031415#pone-0031415-g006" target="_blank">Fig. 6Bii</a>, although this is from a different recording). A temporally magnified view is shown of a single EE-IPSC pair, as indicated by the highlighted region and arrow. Note the long duration of the IPSC (>200 msec) and significantly large amplitude of this event (largest in the entire recording), indicating that the event probably results from a burst of IPSCs. (<b>B</b>) EE-triggered averages of voltage clamp recordings. Time 0 represents the time of onset of a contralateral EE. Only recordings where putative correlated PSCs were found were included in the averaging. Number of extracted windows averaged: IPSCs, n = 26 from 8 slices; EPSCs, n = 30 from 3 slices. The shading represents the ± SE. (<b>C</b>) The mean ± SE for IPSC amplitudes are shown from each neuron as dots, and they are separated into two groups: IPSCs that were paired with a contralateral EE, and IPSCs that were not paired with a contralateral EE. The triangles represent the mean of means for each group, showing a significant difference in the amplitudes of paired vs. unpaired IPSCs (p<0.01 rank sum test).</p

Simultaneous recording of bicuculline EEs in one hemisphere and PSCs in contralateral hemisphere in single neurons.

<p>(<b>Ai</b>) The morphology of a pyramidal neuron in layer 2/3 with a callosal-spanning axon. Inset: response of this neuron to −30 pA and +80 pA current injections, the latter resulting in action potentials. (<b>Aii</b>) The same neuron displayed in <i>Ai</i> is recorded at −70 mV in voltage clamp for 30 minutes while bicuculline is injected into the contralateral hemisphere with a bic. electrode. Black traces are extracellular recordings from the bic. electrode, and the red trace shows EPSCs (as downward deflections) from the neuron. A temporally magnified view of a putative EE-correlated pair of EPSCs is shown, as indicated by the arrow. (<b>Bi</b>) The morphology of a pyramidal neuron in layer 2/3 with a callosally-spanning axon. This neuron was recorded with cesium gluconate in order to better isolate GABA-A IPSCs, and so action potential characterization was not possible in this configuration due to cesium blockade of potassium conductances. (<b>Bii</b>) The same neuron displayed in <i>Bi</i> is recorded at +10 mV in voltage clamp for 30 minutes while bicuculline is injected into the contralateral hemisphere. Black traces are EEs recorded in the bic. electrode, and the blue trace shows IPSCs. Note the long durations of the IPSCs that correlate with the EEs. Temporally magnified views of putative EE-correlated IPSCs are shown, as indicated by arrows.</p

Morphologies of neurons with axons spanning the callosum (axons colored yellow, while somata and dendrites colored white).

<p>Each panel displays the interhemispheric fissure as a reference, and each panel is oriented with the corpus callosum on the bottom, and neuron on the right. <b><i>A</i></b><b>, </b><b><i>B</i></b>, and <b><i>E</i></b> show neurons with asymmetrical apical dendrites that are skewed in a direction away from the callosum. Blebs indicating cut axons were seen in <b><i>A</i></b>, <b><i>B</i></b>, and <b><i>D</i></b> at the end of each respective axon, while the axon appeared to fade from view in <b><i>C</i></b> and <b><i>E</i></b>. Neurons in panels <b><i>D</i></b> and <b><i>E</i></b> are also shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031415#pone-0031415-g006" target="_blank">Fig. 6</a>. The average length of these imaged axons, from cell body to ending in contralateral hemisphere, is 2443±314 µm.</p

Electrophysiological extracellular recordings of bilateral EEs.

<p>(<b>A</b>) 410 µm×410 µm DIC view of the slice, showing the location of two extracellular recording electrodes in each hemisphere (upper left and lower right corners). The interhemispheric fissure forms the rightward slanting diagonal that roughly bisects the image. (<b>B</b>) Two simultaneous extracellular recordings, one hour long, and each from opposite hemispheres in layer 2/3 cingulate cortices show bilateral EEs. 20 µM bicuculline is added to the bath perfusion at the beginning of the recording. These recordings were highpass filtered at 0.2 Hz. Individual bilateral events indicated by arrows are temporally magnified below and are shown without highpass filtering. Sample rate = 5 kHz. Note that the number of events increases per unit time, and the number of afterdischarges per event increases. (<b>C</b>) Complete bisection of the corpus callosum <i>in vitro</i> abolishes bilateral temporal fidelity of EEs (15/15 bilateral events before the cut during 15 minutes of recording, 0/20 bilateral events after the cut during 15 minutes of recording, both with reference to the “blue” recording, p<0.01, Chi Square test of proportions). During a dual extracellular recording in 20 µM bicuculline, a small blade over the corpus callosum is lowered with a micromanipulator, severing all callosal connections during the recording.</p

Differences in bilateral epileptiform activity according to rostral-caudal coordinates of the slice within ACC.

<p>Recordings are grouped according to slice number, where each slice increment represents a 350 µm increment caudally from the most rostral part of the corpus callosum, and slice 1 is the first slice to show an intact callosum as slices are taken from rostral to caudal. (<b>A</b>) Calcium imaging data from a total of 101 slices, each recorded for approximately 2 minutes. Proportions of slices that yielded no evidence of bilateralization are shown (i.e., no cells recorded in separate hemispheres with simultaneous calcium transients). The caudal slices were more likely to demonstrate bilateral EEs. (<b>B</b>) and (<b>C</b>) Data from 30–60 minute-long long extracellular electrophysiological recordings. For the BIC group (20 µM bicuculline), n = 1, 8, 4, and 4 for slices 1–4, respectively, while for the BIC+MK801 group (20 µM bicuculline+10 µM MK-801), n = 2, 5, 5, and 5 for slices 1–4, respectively. (<b>B</b>) The proportion of unilateral EEs in each recording is smaller for caudal slices than rostral slices within ACC. For the BIC group, there is a significant difference in these values between the slice 4 and slice 2 groups. Note a similar trend in the BIC+MK801 group. (<b>C</b>) The interhemispheric latencies (IHLs) are shorter for caudal slices than in rostral slices, for both the BIC and BIC+MK801 groups.</p