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9731_13 | Since 2012, the use of cryogen-free magnet technology has greatly reduced infrastructure requirements and dependency on the availability of increasingly hard to obtain cryogenic coolants.
Strengths: The advantage of micro-MRI is that it has good spatial resolution, up to 100 µm and even 25 µm in very high strength magnetic fields. It also has excellent contrast resolution to distinguish between normal and pathological tissue. Micro-MRI can be used in a wide variety of applications, including anatomical, functional, and molecular imaging. Furthermore, since micro-MRI's mechanism is based on a magnetic field, it is much safer compared to radiation based imaging modalities such as micro-CT and micro-PET. |
9731_14 | Weaknesses: One of the biggest drawbacks of micro-MRI is its cost. Depending on the magnetic strength (which determines resolution), systems used for animal imaging between 1.5 and 14 teslas in magnetic flux density range from $1 million to over $6 million, with most systems costing around $2 million. Furthermore, the image acquisition time is extremely long, spanning into minutes and even hours. This may negatively affect animals that are anesthetized for long periods of time. In addition, micro-MRI typically captures a snapshot of the subject in time, and thus it is unable to study blood flow and other real-time processes well. Even with recent advances in high strength functional micro-MRI, there is still around a 10–15 second lag time to reach peak signal intensity, making important information such as blood flow velocity quantification difficult to access. |
9731_15 | Cancer research: Micro-MRI is often used to image the brain because of its ability to non-invasively penetrate the skull. Because of its high resolution, micro-MRI can also detect early small-sized tumors. Antibody-bound paramagnetic nanoparticles can also be used to increase resolution and to visualize molecular expression in the system.
Stroke and traumatic brain injury research: Micro-MRI is often used for anatomical imaging in stroke and traumatic brain injury research. Molecular imaging is a new area of research.
Micro-CT |
9731_16 | Principle: Computed tomography (CT) imaging works through X-rays that are emitted from a focused radiation source that is rotated around the test subject placed in the middle of the CT scanner. The X-ray is attenuated at different rates depending on the density of tissue it is passing through, and is then picked up by sensors on the opposite end of the CT scanner from the emission source. In contrast to traditional 2D X-ray, since the emission source in a CT scanner is rotated around the animal, a series of 2D images can then be combined into 3D structures by the computer. |
9731_17 | Strengths: Micro-CT can have excellent spatial resolution, which can be up to 6 µm when combined with contrast agents. However, the radiation dose needed to achieve this resolution is lethal to small animals, and a 50 µm spatial resolution is a better representation of the limits of micro-CT. It is also decent in terms of image acquisition times, which can be in the range of minutes for small animals. In addition, micro-CT is excellent for bone imaging. |
9731_18 | Weaknesses: One of the major drawbacks of micro-CT is the radiation dosage placed on test animals. Although this is generally not lethal, the radiation is high enough to affect the immune system and other biological pathways, which may ultimately change experimental outcomes. Also, radiation may affect tumor size in cancer models as it mimics radiotherapy, and thus extra control groups might be needed to account for this potential confounding variable. In addition, the contrast resolution of micro-CT is quite poor, and thus it is unsuitable for distinguishing between similar tissue types, such as normal vs. diseased tissues. |
9731_19 | Cancer research: Micro-CT is most often used as an anatomical imaging system in animal research because of the benefits that were mentioned earlier. Contrast agents can also be injected to study blood flow. However, contrast agents for micro-CT, such as iodine, are difficult to conjugate molecular targets1 with, and thus it is rarely used in molecular imaging techniques. As such, micro-CT is often combined with micro-PET/SPECT for anatomical and molecular imaging in research. |
9731_20 | Micro-PET
Principle: Positron Emission Tomography (PET) images living systems by recording high-energy γ-rays emitted from within the subject. The source of the radiation comes from positron-emitting-bound biological molecules, such as 18F-FDG (fludeoxyglucose), which is injected into the test subject. As the radioisotopes decay, they emit positrons which annihilates with electrons found naturally in the body. This produces 2 γ-rays at ~180° apart, which are picked up by sensors on opposite ends of the PET machine. This allows individual emission events to be localized within the body, and the data set is reconstructed to produce images. |
9731_21 | Strengths: The strength of micro-PET is that because the radiation source is within the animal, it has practically unlimited depth of imaging. The acquisition time is also reasonably fast, usually around minutes. Since different tissues have different rates of uptake radiolabelled molecular probes, micro-PET is also extremely sensitive to molecular details, and thus only nanograms of molecular probes are needed for imaging. |
9731_22 | Weaknesses: Radioactive isotopes used in micro-PET have very short half-lives (110 min for 18F-FDG). In order to generate these isotopes, cyclotrons in radiochemistry laboratories are needed in close proximity of the micro-PET machines. Also, radiation may affect tumor size in cancer models as it mimics radiotherapy, and thus extra control groups might be needed to account for this potential confounding variable. Micro-PET also suffers from poor spatial resolution of around 1 mm. In order to conduct a well rounded research that involves not only molecular imaging but also anatomical imaging, micro-PET needs to be used in conjunction with micro-MRI or micro-CT, which further decreases accessibility to many researchers because of high cost and specialized facilities. |
9731_23 | Cancer research: PET is usually widely used in clinical oncology, and thus results from small animal research are easily translated. Because of the way 18F-FDG is metabolized by tissues, it results in intense radiolabelling in most cancers, such as brain and liver tumors. Almost any biological compound can be traced by micro-PET, as long as it can be conjugated to a radioisotope, which makes it suitable towards studying novel pathways.
Micro-SPECT
Principle: Similar to PET, single photon emission computed tomography (SPECT) also images living systems through γ-rays emitted from within the subject. Unlike PET, the radioisotopes used in SPECT (such as technetium-99m) emit γ-rays directly, instead of from annihilation events of a positron and electron. These rays are then captured by a γ-camera rotated around the subject and subsequently rendered into images. |
9731_24 | Strengths: The benefit of this approach is that the nuclear isotopes are much more readily available, cheaper, and have longer half-lives as compared to micro-PET isotopes. Like micro-PET, micro-SPECT also has very good sensitivity and only nanograms of molecular probes are needed. Furthermore, by using different energy radioisotopes conjugated to different molecular targets, micro-SPECT has the advantage over micro-PET in being able to image several molecular events simultaneously. At the same time, unlike micro-PET, micro-SPECT can reach very high spatial resolution by exploring pinhole collimation principle (Beekman et al.) In this approach, by placing the object (e.g. rodent) close to the aperture of the pinhole, one can reach high magnification of its projection on detector surface and effectively compensate for intrinsic resolution of the crystal. |
9731_25 | Weaknesses: Micro-SPECT still has considerable radiation which may affect physiological and immunological pathways in the small animals. Also, radiation may affect tumor size in cancer models as it mimics radiotherapy, and thus extra control groups might be needed to account for this potential confounding variable. Micro-SPECT can also be up to two orders of magnitude less sensitive than PET. Furthermore, labeling compounds with micro-SPECT isotopes require chelating molarities which may alter their biochemical or physical properties.
Cancer research: Micro-SPECT is often used in cancer research for molecular imaging of cancer-specific ligands. It can also be used to image the brain because of its penetration power. Since newer radioisotopes involve nanoparticles such as 99mTC-labelled iron oxide nanoparticles, they could potentially be combined with drug delivery systems in the future. |
9731_26 | The following small-animal SPECT systems have been developed in different groups and are available commercially:
Combined PET-MR
Principle: The PET-MR technology for small animal imaging offers a major breakthrough in high performance functional imaging technology, particularly when combined with a cryogen-free MRI system. A PET-MR system provides superior soft tissue contrast and molecular imaging capability for great visualisation, quantification and translational studies. A PET-MR preclinical system can be used for simultaneous multi-modality imaging. Use of cryogen-free magnet technology also greatly reduces infrastructure requirements and dependency on the availability of increasingly hard to obtain cryogenic coolants. |
9731_27 | Strengths: Researchers can use standalone PET or MRI operation, or use multi-modality imaging. PET and MRI techniques can be carried out either independently (using either the PET or MRI systems as standalone devices), or in sequence (with a clip-on PET) in front of the bore of the MRI system, or simultaneously (with the PET inserted inside the MRI magnet). This provides a much more accurate picture far more quickly. By operating the PET and MRI systems simultaneously workflow within a laboratory can be increased. The MR-PET system from MR Solutions incorporates the latest technology in Silicon Photomultipliers (SiPM), which significantly reduces the size of the system and avoids the problems of using photomultipliers or other legacy detector types within the magnetic field of the MRI. The performance characteristics of SiPM are similar to a conventional PMT, but with the practical advantages of solid-state technology. |
9731_28 | Weaknesses: As this is a combination of imaging systems the weaknesses associated with each imaging modality are largely compensated for by the other. In sequential PET-MR, the operator needs to allow a little time to transfer the subject between the PET and MR acquisition positions. This is negated in simultaneous PET-MR. However, in sequential PET-MR systems, the PET ring itself is easy to clip-on or off and transfer between rooms for independent use. The researcher requires sufficient knowledge to interpret images and data from the two different systems and would require training for this. |
9731_29 | Cancer research: The combination of MR and PET imaging is far more time efficient than using one technique at a time. Images from the two modalities may also be registered far more precisely, since the time delay between modalities is limited for sequential PET-MR systems, and effectively non-existent for simultaneous systems. This means that there is little to no opportunity for gross movement of the subject between acquisitions.
Combined SPECT-MR
Principle: The new SPECT-MR for small animal imaging is based on multi-pinhole technology, allowing high resolution and high sensitivity. When coupled with cryogen-free MRI the combined SPECT-MR technology dramatically increases the workflow in research laboratories whilst reducing laboratory infrastructure requirements and vulnerability to cryogen supply. |
9731_30 | Strengths: Research facilities no longer need to purchase multiple systems and may choose between different system imaging configurations. The SPECT or MRI equipment can each be used as a standalone device on a bench, or sequential imaging can be carried out by clipping the SPECT module on to the MRI system. The animal translates automatically from one modality to the other along the same axis. By inserting a SPECT module inside the MRI magnet simultaneous acquisition of SPECT and MRI data is possible. The workflow of the laboratory can be increased by acquiring multiple modalities of the same subject in one session or by operating the SPECT and MRI systems separately, imaging different subjects at the same time. SPECT-MR is available in different configurations with different trans-axial field of views, allowing imaging from mice to rats. |
9731_31 | Weaknesses: As this is a combination of imaging systems the weaknesses associated with one or other imaging modality are no longer applicable. In sequential SPECT-MR, the operator needs to allow a little time to transfer the subject between the SPECT and MR acquisition positions. This is negated in simultaneous SPECT-MR. However, for sequential SPECT-MR, when the SPECT module is clipped on it is easy to clip-on or off and transfer between rooms. The researcher has to have sufficient knowledge to interpret two different system outputs and would require training for this. |
9731_32 | Cancer research: The combination of MRI, which is used as a non-invasive imaging technique, and SPECT provide results far more quickly when compared to using one technique at a time. Images from the two modalities may also be registered far more precisely, since the time delay between modalities is limited for sequential SPECT-MR systems, and effectively non-existent for simultaneous systems. This means that there is little to no opportunity for gross movement of the subject between acquisitions. With separate, independent operation of the MRI and SPECT systems workflow can easily be increased.
Optical imaging
Principle: Optical imaging is divided into fluorescence and bioluminescence. |
9731_33 | Fluorescence imaging works on the basis of fluorochromes inside the subject that are excited by an external light source, and which emit light of a different wavelength in response. Traditional fluorochromes include GFP, RFP, and their many mutants. However significant challenges emerge in vivo due to the autofluorescence of tissue at wavelengths below 700 nm. This has led to a transition to near-infrared dyes and infrared fluorescent proteins (700 nm–800 nm) which have demonstrated much more feasibility for in vivo imaging due to the much lower autofluorescence of tissue and deeper tissue penetration at these wavelengths. |
9731_34 | Bioluminescence imaging, on the other hand, is based on light generated by chemiluminescent enzymatic reactions. In both fluorescence and bioluminescence imaging, the light signals are captured by charged coupled device (CCD) cameras cooled up to −150 °C, making them extremely light-sensitive. In events where more light is produced, less sensitive cameras or even the naked eye can be used to visualize the image. |
9731_35 | Strengths: Optical imaging is fast and easy to perform, and is relatively inexpensive compared to many of the other imaging modalities. Furthermore, it is extremely sensitive, being able to detect molecular events in the 10–15 M range. In addition, since bioluminescence imaging does not require excitation of the reporter, but rather the catalysis reaction itself, it is indicative of the biological / molecular process and has almost no background noise. |
9731_36 | Weaknesses: A major weakness of optical imaging has been the depth of penetration, which, in the case of visible dyes is only a few millimeters. Near-infrared fluorescence has allowed depths of several centimeters to be feasible. Since light in the infrared region has the best penetration depth, numerous fluorochromes have been specifically designed to be optimally excited in this area. Optical imaging, fluorescence has a resolution limited to the diffraction of light of ~270 nm and bioluminescence has a resolution of ~1–10 mm, depending on time of acquisition, compared to MRI at 100 µm, and micro-ultrasound at 30 µm. |
9731_37 | Cancer research: Because of poor depth of penetration, optical imaging is typically only used for molecular purposes, and not anatomical imaging. Due to poor depth of penetration in visible wavelengths, it is used for subcutaneous models of cancer, however near-infrared fluorescence has enabled orthotopic models to now be feasible. Often, investigation of specific protein expression in cancer and drug effects on these expressions are studied in vivo with genetically engineered light-emitting reporter genes. This also allows the identification of mechanisms for tissue-selective gene targeting in cancer and beyond.
Combined PET-optical imaging, fluorescence |
9731_38 | Principle: Dioxaborolane chemistry enables radioactive fluoride (18F) labeling of antibodies or red blood cells, which allows for positron emission tomography (PET) and fluorescence imaging of cancer and hemorrhages, respectively. A Human-Derived, Genetic, Positron-emitting and Fluorescent (HD-GPF) reporter system uses a human protein, PSMA and non-immunogenic, and a small molecule that is positron-emitting (boron bound 18F) and fluorescent for dual modality PET and fluorescence imaging of genome modified cells, e.g. cancer, CRISPR/Cas9, or CAR T-cells, in an entire mouse. The combining of these imaging modalities was predicted by 2008 Nobel Laureate, Roger Y. Tsien, to compensate for the weaknesses of single imaging techniques. |
9731_39 | Strengths: Combines the strengths of PET and optical Imaging, fluorescence. PET allows for anatomical imaging for location of labelled cells in entire animals or humans because the radiolabel, 18F, is within the animal or human for nearly unlimited depth of penetration. 18F has a half-life of 110 min and limits the radioactive exposure to the animal or human. Optical imaging allows for higher resolution with sub-cellular resolution of ~270 nm, or the diffraction limit of light, to allow for imaging of single cells and localizing cellular location on the cell membrane, endosomes, cytoplasm, or nuclei (see FIgure of multicolor HeLa cellls). The technique can label small molecules, antibodies, cells (cancer and red blood cells), cerebrospinal fluid, hemorrhages, prostate cancer removal, and genome edited cells expressing a genetically encoded human protein, PSMA, for imaging CRISPR/Cas9 edited and CAR T-cells. |
9731_40 | Weaknesses: Combining PET and optical imaging allows for two imaging agents that compensate for the weakness of the others. 18F has a half-life of 110 min and the PET signal is not permanent. Fluorescent small molecules allow for permanent signal when stored in the dark and not photobleached. Currently, there is not a single instrument that can image the PET signal and image fluorescence with subcellular resolution (see Figure of multicolor HeLa cells). Multiple instruments are required to image PET, whole organ fluorescence, and single cell fluorescence with sub-cellular resolution.
References
Imaging
Medical physics
Medical imaging |
9732_0 | On the morning of September 4, 2005, six days after Hurricane Katrina struck New Orleans, members of the New Orleans Police Department (NOPD), ostensibly responding to a call from an officer under fire, shot and killed two civilians at the Danziger Bridge: 17-year-old James Brissette and 40-year-old Ronald Madison. Four other civilians were wounded. All the victims were African-American. None were armed or had committed any crime. Madison, a mentally disabled man, was shot in the back. The shootings caused public anger and further eroded the trust New Orleans had in the federal response to Hurricane Katrina and the NOPD.
The NOPD attempted to cover-up the killings, falsely reporting that seven police officers responded to a police dispatch reporting an officer down, and that at least four suspects were firing weapons at the officers upon their arrival. Rev. Raymond Brown, the local head of the National Action Network, described the shootings as "...a racial tragedy." |
9732_1 | On August 5, 2011, a federal jury in New Orleans convicted five NOPD officers of myriad charges related to the cover-up and deprivation of civil rights. An attorney for the Justice Department described the case as "the most significant police misconduct prosecution [in the U.S.] since the Rodney King beating case". However, the convictions were vacated on September 17, 2013, due to prosecutorial misconduct, and a new trial was ordered. The Justice Department appealed the decision to vacate the convictions, but a federal appeals court agreed that a new trial was warranted. However, on April 20, 2016; the five former officers pleaded guilty to various charges related to the shooting, and in return received reduced sentences ranging from three to twelve years. Three of the officers are white and two are African-American. |
9732_2 | Shooting on the bridge
On September 4, 2005, almost a week after Hurricane Katrina struck New Orleans, several New Orleans Police Department (NOPD) officers arrived at the Danziger Bridge. The officers involved included Sgt. Kenneth Bowen, Sgt. Robert Gisevius, Officer Anthony Villavaso, and Officer Robert Faulcon. The officers arrived in a Budget rental truck; none of them were in uniform; and they were armed with rifles including AK-47s, at least one of which was unauthorized, and an M4 carbine assault rifle. A witness, Kasimir Gaston, described the men as lining up "like at a firing range". The officers opened fire without warning on the Bartholomew family and friend, who had been walking to a grocery store and were then sheltering behind a concrete barrier. |
9732_3 | As a result of this initial shooting, 17-year-old James Brissette — a family friend — was killed. Four other civilians were wounded. Susan Bartholomew's arm was partially shot off and later had to be amputated. Her husband, Leonard, was shot in the back, head and foot. The Bartholomews' teenage daughter Lesha was shot four times. Jose Holmes Jr., a friend of Brissette's, was shot in the abdomen, the hand and the jaw. |
9732_4 | Two brothers who fled the scene, Ronald and Lance Madison, were pursued down the bridge by officers Gisevius and Faulcon in an unmarked state police vehicle. Faulcon fired his shotgun from the back of the car at Ronald, a developmentally disabled man who later died from his injuries. The autopsy found that Ronald Madison sustained seven gunshot wounds, five of them in his back. Bowen was later convicted of stomping Madison on the back before he died, though this conviction was overturned for lack of physical evidence. Lance Madison was then taken into custody and charged with eight counts of attempting to kill police officers. He was held in custody for three weeks before being released without indictment.
No weapons were recovered at the scene, and both police and civilian witnesses testified that the victims had been unarmed. Later investigation showed that some shots had been fired in the area by trapped residents attempting to attract the attention of rescuers. |
9732_5 | Initial investigation and cover-up
The NOPD shooters stated that while approaching the Danziger Bridge, they had been fired on by civilians, and were forced to return fire. Homicide detective Arthur "Archie" Kaufman was made the lead investigator on the case. He was later found guilty of conspiring with the defendants to conceal evidence in order to make the shootings appear justified, including fabricating information for his official reports on the case. NOPD Lieutenant Michael Lohman also encouraged the officers to "provide false stories about what had precipitated the shooting" and plant a firearm near the scene. |
9732_6 | Continued investigation
The officers involved in the shooting were taken into custody on January 2, 2007, and were indicted for murder and attempted murder. Gisevius, Bowen, and Villavaso were charged with the first-degree murder of Brissette. Faulcon was charged with the first-degree murder of Madison. Those officers, as well as NOPD officers Michael Hunter, Ignatius Hills and Robert Barrios, were indicted on charges of attempted murder relating to the other four victims. On August 13, 2008, the indictments were dismissed by District Judge Raymond Bigelow due to prosecutorial misconduct. Bigelow found that the prosecutors had wrongly instructed the grand jury, improperly used grand jury testimony against three of the defendants, and divulged grand jury testimony to a witness in the case. |
9732_7 | Two weeks later, the FBI and the Civil Rights Division of the U.S. Department of Justice began investigating the case. U.S. Attorney Jim Letten of the Eastern District of Louisiana vowed his office would take "as much time and resources as necessary" to resolve the case.
In 2010, the investigation resulted in a series of guilty pleas from participants in the cover-up. On February 24, 2010, Lohman entered a plea of guilty to obstruction of justice in federal court. On March 11, Jeffrey Lehrmann, another former NOPD officer, pleaded guilty to misprision of a felony for failing to report the cover-up. On April 7, Michael Hunter, one of the seven officers originally charged with attempted murder in 2007, pleaded guilty to misprision of a felony and obstruction of justice. Hunter later became a key witness in the case against Bowen, Gisevius, Faulcon, and Villavaso. |
9732_8 | On April 16, Barrios was charged with one count of conspiring to obstruct justice, becoming the fourth NOPD officer to be federally charged in the case. He promptly resigned from the force. A fifth man, Marion David Ryder, a civilian who witnessed the incident and falsely represented himself as a law enforcement officer, was also charged in the case. He was accused of lying to the FBI about the event when he claimed that one of the victims had a weapon. On April 28, he pleaded guilty to the charges. On May 21, Hills was charged by a bill of information with one count of conspiring to obstruct justice and one count of misprision of a felony, becoming the fifth NOPD officer to be federally charged. He had resigned from the force the previous day. A former police officer stated at Hills' trial that he had used a racial slur in later describing how he tried to "pop a round off" at 14-year-old Leonard Bartholomew. Hill and Bartholomew are both African-American. |
9732_9 | On July 13, 2010, a federal grand jury indicted Bowen, Gisevius, Faulcon, and Villavaso in connection with the shooting and subsequent cover-up. Additionally, Kaufman and Gerard Dugue, the original investigators in the case, were charged with falsifying reports and false prosecution in the conspiracy to cover up the shooting. While the federal government lacked jurisdiction to file murder charges in the case, they were able to file charges under federal civil rights statutes intended to enforce Section 1 of the Fourteenth Amendment. Under Title 18 U.S.C. Section 242, "Deprivation of Rights Under Color of Law", anyone who acts, under color of law, to unlawfully deprive a citizen of their right to life, may be sentenced to death. |
9732_10 | Sentencing
Guilty verdicts were handed down for Bowen, Gisevius, Faulcon, Villavaso and Kaufman on August 5, 2011. On April 4, 2012, District Judge Kurt D. Engelhardt sentenced Faulcon to 65 years' imprisonment, Bowen and Gisevius to 40 years, Villavaso to 38 years, and Kaufman to six years. Engelhardt was critical of how the prosecution had been pursued, stating that he was "astonished and deeply troubled" by the number of plea bargains offered to other participants who served as witnesses. Federal prosecutors responded that the plea bargains had been necessary for a difficult case that had been "cold" when they assumed responsibility.
Gerard Dugue, who is alleged to have conspired in the cover-up with Kaufman, had his original hearing ruled a mistrial in January 2012. His retrial was postponed to allow for appellate court petitions from both the prosecution and defense, and was set for March 11, 2013, then delayed and set for May 13, but was later delayed indefinitely. |
9732_11 | Retrial ordered
On May 18, 2012, a month after they were convicted, the five officers appealed their convictions, arguing that federal prosecutors had engaged in a public relations campaign against their clients by anonymously posting comments on NOLA.com, the website of New Orleans newspaper The Times-Picayune. Principally, the defendants cited comments made by Sal Perricone, the former top trial attorney for the Eastern District (though Perricone was not involved in the prosecution of the Danziger Bridge case). Perricone's activities had been exposed in March 2012 in an unrelated case, and he had resigned soon afterward. |
9732_12 | On September 17, 2013, following a year-long probe into the defendants' claims, Judge Engelhardt vacated the convictions of Bowen, Faulcon, Gisevius, Villavaso and Kaufman, and ordered a new trial. In his decision, Engelhardt cited what he called "highly unusual, extensive and truly bizarre actions" by prosecutors; specifically, leaks to certain media outlets and comments that were posted by members of the U.S. Attorney's Office in online forums. The probe revealed that Perricone had made numerous posts attacking the NOPD as early as 2008, and had also made posts urging witnesses to join Lohman in pleading guilty. It also revealed that Perricone and Justice Department official Karla Dobinski had made posts regarding trial testimony while the trial was underway. Dobinski was the head of a Justice Department "taint team" that was to help ensure testimony Bowen gave to the state grand jury wasn't used improperly. The Justice Department appealed Engelhardt's decision to the United States |
9732_13 | Court of Appeals for the Fifth Circuit, however, a panel of judges upheld the ruling in a 2-1 decision. |
9732_14 | Guilty pleas
On April 20, 2016, five former officers pleaded guilty to charges of deprivation of rights under color of law, obstruction of justice, and conspiracy to obstruct justice. In return, they were sentenced to significantly reduced sentences of three to twelve years in prison, with credit for time served. Gisevius' attorney, Eric Hessler, later said a number of potential witnesses in the planned retrial were too afraid to testify. In addition to the online commenting scandal, several witnesses had been threatened by prosecutors and investigators. According to Hessler, this left no option but to accept a plea bargain. Those who pleaded guilty included the four former officers who took part in the shootings and the former officer who covered up the incident after it happened. |
9732_15 | On November 4, 2016, Dugue pleaded guilty in federal court to "a misdemeanor charge of accessory after the fact to deprivation of rights under the color of law". He was sentenced to one year of probation, making him the only NOPD officer who plead guilty in the case but was not sent to prison. Dugue's sentencing marked the end of the criminal cases against the police officers involved in the shootings and cover-up.
Civil lawsuits and settlement
Four civil lawsuits involving eight plaintiffs and seventeen defendants had been filed in federal court, but were on hold until the criminal cases were resolved. Defendants in the civil lawsuits included the City of New Orleans, the NOPD, a former police chief and assistant chief, and Mayor Ray Nagin. The four lawsuits were consolidated before U.S. District Judge Jane Triche Milazzo. |
9732_16 | On December 19, 2016, New Orleans Mayor Mitch Landrieu announced a settlement agreement between the city and the families of the Danziger Bridge shootings, plus two other cases involving "lethal confrontations between officers and civilians in the aftermath of Hurricane Katrina. The settlement includes payments for the families of victims killed or injured in the shooting of unarmed civilians on the Danziger Bridge; for the beating death of Raymond Robair, 48, who was killed before the storm; and for the fatal shooting of Henry Glover, who was killed by a police officer standing guard outside an Algiers shopping center."
As part of his news conference announcing the settlement, Mayor Landrieu also issued a verbal apology to the families of all of the victims, which is considered rare for any city leader to do in cases of proven police brutality. The settlement was also revealed to have totaled $13.3 million
Timeline of events |
9732_17 | See also
Crime in Louisiana
Death of Henry Glover
Effects of Hurricane Katrina in New Orleans
List of killings by law enforcement officers in the United States
References
Further reading
External links
Grand Jury Indictment at the Times Picayune
NPR.org story about guilty pleas
2005 in Louisiana
Deaths by firearm in Louisiana
Police brutality in the United States
+Danziger
Crimes in New Orleans
2005 murders in the United States
Attacks in the United States in 2005
21st century in New Orleans
+Danziger |
9733_0 | Columbus Union Station was an intercity train station in Downtown Columbus, Ohio, near The Short North neighborhood. The station and its predecessors served railroad passengers in Columbus from 1851 until April 28, 1977. |
9733_1 | The first station building was the first union station in the world, built in 1851. Its replacement was built from 1873 to 1875, just before demolition of the first station building. After traffic problems on High Street, as well as increased rail traffic became problematic, a new station was planned by Daniel Burnham beginning in 1893. The new station opened in 1897, and its arcade along High Street was finished in 1899. By 1928, part of the arcade was demolished. Passenger service significantly declined from the 1950s to the 1970s. The arcade was demolished in 1976 to make way for a new convention center, although it had been placed on the National Register of Historic Places two years prior. Train service stopped at Union Station in 1977, and the remaining portions of the station were demolished in 1979. The demolished arcade was delisted in 1999. A portion of the arcade was saved, the Union Station arch, which is the focal point of the McFerson Commons park in the nearby Arena |
9733_2 | District. |
9733_3 | Services
The first station initially was operated by the Columbus and Xenia Railroad (C&X) and Cleveland, Columbus and Cincinnati Railroad (CC&C), with the Central Ohio Railroad and Columbus, Piqua and Indiana Railroads joining in 1853. In 1864, the Steubenville and Indiana Railroad also began operating at the station. |
9733_4 | Major trains in the 1940s included:
Baltimore and Ohio
No.#33/38, #35/36 - (Cincinnati - Pittsburgh)
Chesapeake and Ohio
Sportsman (Detroit - Washington, D.C. and Newport News, Virginia)
New York Central
Cincinnati Mercury (Cincinnati - Cleveland)
Cleveland Special / Cincinnati Special (Cincinnati - Cleveland)
Midnight Special (Cincinnati - Cleveland)
Ohio State Limited (Cincinnati - New York City)
Southwestern Limited (St. Louis - New York City)
Norfolk and Western
branch of Pocahontas from Portsmouth, Ohio, eastern destination: Norfolk, Virginia)
Pennsylvania Railroad
American (St. Louis - New York City)
Indianapolis Limited (Indianapolis - New York City)
Penn Texas (St. Louis - New York City)
Spirit of St. Louis (St. Louis - New York City)
St. Louisan (St. Louis - New York City)
Interurban company:
Cincinnati and Lake Erie Railroad
Station attributes |
9733_5 | Union Station was designed by Daniel Burnham. He was noted at the time as one of the primary architects of the World's Columbian Exposition, which utilized Beaux-Arts designs to resemble a prototype for an ideal city, ushering in the City Beautiful movement.
Burnham's use of the style lead to an ornate station, held in awe by Columbusites for many years, though by the time of its deterioration in the 1970s, it was largely overlooked.
Archway ornamentation
The two main arched entranceways consisted of recessed semicircular arches, each flanked by four fluted round Corinthian columns. Two angel reliefs were carved into each of the arches' extradoes. The arches had friezes, with decorative eagle medallions. Above this was a denticulated cornice, and above that, a wider frieze with triglyphs and alternating medallions with classical busts. Above that was another denticulated cornice with gargoyles. The pedestals above the Corinthian columns featured statue groups. |
9733_6 | The arcade's smaller arches were supported at the spring line by fluted Doric columns. The arches had similar motifs, but were only reached to the base of the larger arches' friezes.
Each of the arches had wood lath vaulted ceilings, covered in plaster. By 1973, the plaster was crumbling, and the arches became nesting places for pigeons, while moisture was causing the wood lath to rot. Storefronts were set behind the arches, all vacant by 1973 except a cigar store.
History
Columbus Union Station, as it is recalled today, was the third Union Station in Columbus. The previous two served in the nineteenth century, and their replacement and upgrade reflected the rapid growth in traffic and importance of Columbus' railroads at that time. The subsequent decline in rail passenger traffic following World War II was reflected in Union Station's demolition and replacement with a convention center in the early 1980s.
First station (1851) |
9733_7 | In 1851, a site north of Naughten Street and east of High Street was purchased jointly from Orange Johnson by the Columbus and Xenia Railroad (C&X) and Cleveland, Columbus and Cincinnati Railroad (CC&C). A wood barn structure measuring was installed to serve passengers, the rest of the site given over to shops and freight tracks. The station had three tracks for loading and unloading of passengers. This station was the first union station in the world, housing multiple railroad companies, although the first Indianapolis Union Station was being planned, and involved more railroad cooperation than the Columbus station had, and a more equal ownership stake. |
9733_8 | In 1853, the Central Ohio and Columbus, Piqua and Indiana Railroads entered the city and connected to the station. In 1864, the Steubenville and Indiana Railroad was connected the Central Ohio at Newark, and entered the station on shared tracks. This road was called the "panhandle route" because it crossed the panhandle of West Virginia on its way east. The station was inadequate and in 1868 the railroads formed the Union Depot Company to undertake a replacement.
The second station (1875)
In May 1873, work was begun on the second union station north of the existing station, and it opened on February 14, 1875. The first station was then demolished. Compared to its wooden predecessor, this new station was far more substantial. Constructed of brick, it had a large waiting room, ticket offices and railroad offices at the front of the structure. Seven tracks entered the structure and a long train shed kept passengers dry. In 1875, 42 daily passenger trains departed from the station. |
9733_9 | High Street crossing
The City of Columbus continued to grow northward with the opening of Ohio State University in 1870. With the opening of the new union station, thirteen tracks now crossed North High Street. The congestion between train and road traffic became unbearable. In 1875, a $45,000 tunnel was built under the tracks to allow streetcars and horsecarts to pass under the tracks. An extra mule was stationed at the tunnel entrance to assist horsecars up the steep grade. The tunnel was long with approaches on either side. It was so dark and smelly that only the horsecar passengers, who had no other choice, would use it.
The third station (1897)
In 1891 the traffic situation on High Street reached a crisis, with the roadway blocked for up to seven hours per day by crossing trains. As well, the Columbus Board of Trade (the city's chamber of commerce) rallied for support of a modern and grand station to fit their view of the city. |
9733_10 | In 1893 the architectural firm of Daniel H. Burnham & Company of Chicago began planning a new facility. A key feature of the new station would be a road viaduct over the tracks, finally solving the traffic/train problem on North High Street. In 1893 the old station was handling 112 passenger trains per day.
The new station opened in 1897, and the arcade was finished in 1899. The arcade was unique to Columbus and consisted of stores and offices built atop the viaduct and facing High Street. An elevated roadway connected High Street to the station to the east. The station increased the number of depot tracks from seven to nine.
The architecture of the station drew on Burnham's experience designing the Chicago World's Fair in 1893. The style was Beaux-Arts Classicism, a late 19th-century style often applied to monumental structures. |
9733_11 | In May 1928, part of the arcade was demolished to expand the driveway to the station to better accommodate automobiles. Service moved from the Toledo and Ohio Central Railroad Station to Union Station in 1930. In April 1931, the train shed was replaced with an enclosed concourse. In 1956, Columbus was down to 42 daily passenger trains, the lowest number since 1875.
Daily passenger trains fell to 21 in 1962, and just 10 in 1970. It was clear that the completion of the interstates and popularity of automobiles would soon mean the end of passenger rail service in Columbus. On May 1, 1971, Amtrak took over most of what was left of passenger service in the United States. On January 17, 1974, the station's arcade was listed on the National Register of Historic Places, noted in emergency as plans existed to demolish the structure.
Decline and demolition (1976–1979) |
9733_12 | Amtrak cut back rail service to a single train, the New York-Kansas City National Limited (formerly the Spirit of St. Louis). The restaurant and newsstand were closed.
The demolition and replacement of Union Station dates to a 1969-1975 lawsuit against the Columbus-based Battelle Memorial Institute (BMI). The institute was formed as a nonprofit and still operates as one, though its improper profit uses led to the lawsuit. As a result, BMI offered about $80 million for various causes, including $36.5 million to establish a convention center at the site of Union Station. BMI established the Battelle Commons Corporation in 1974 to handle the project. |
9733_13 | Battelle Commons Corporation applied for grants to create a transit center as part of the convention center, including from the Urban Mass Transit Administration (UMTA) and Federal Highway Administration. The transit center project was supported by the Central Ohio Transit Authority (COTA), Columbus's mass transit agency. The proposed hub, titled TransCenter, was to include 2,000 square feet inside the restored Union Station arcade, containing transit information, ticket offices, a bus waiting and loading area, and entranceways to transit below street-level. A new 20,000-square-foot bus facility and COTA office was to be constructed alongside the arcade. The proposed funding included $6.24 million from the UMTA for buildings and platforms, $1.05 million from the Federal Railroad Administration for restoring the arcade, and Battelle contributing $1.56 million for the building and platforms, and $450,000 for the arcade. The combined project was to cost $9.3 million. It was noted that |
9733_14 | Battelle made no effort to find funding from obvious sources including the State Historic Preservation Office, the National Endowment for the Arts, Department of the Interior, Community Development Block Grants, or General Revenue Sharing Funds. |
9733_15 | On October 19, 1976, Battelle's trustees decided to demolish the station, stating it would be an "imprudent use of Battelle's money", even though it was noted to be a small portion. The organization gave no warning to outside organizations. The State Historic Preservation was not advised, nor was COTA; COTA's executive director stated the public mistakenly blamed it for the demolition. The City of Columbus also stated it was not involved in the decision, but knew Battelle was considering it. Battelle believed the demolition would not block the pending federal funding. |
9733_16 | At 6 pm on Friday, October 22, 1976, S.G. Loewendick & Sons demolished nearly the entire arcade. By 6 pm on the next day, a temporary restraining order secured by the Ohio Historical Society halted the demolition. The order noted that improper procedures were followed in planning its demolition. Battelle then allowed the historical society 120 days to remove the remaining remnant of the demolition, a single arch left standing; Battelle offered no funds to help preserve or move the arch. COTA's director still expressed his desire for TransCenter to be built, despite the arcade's loss. Battelle published development plans with the arcade removed as soon as October 24. The arcade's demolition prompted the UMTA to withdraw all $6.24 million in funding, stating the act violated the spirit of the law and was inconsistent with UMTA requirements. |
9733_17 | While the arcade was gone, Union Station continued to serve rail passengers until the morning of April 28, 1977. On that date, Amtrak moved its operations to a metal shed ("Amshack") east of the station near the 4th Street viaduct when it became apparent that the cost of operating the station was too great. The last train to serve the main station building was a westbound National Limited, which left for Kansas City at 9:17 am that morning.
The station was finally demolished in September 1979. The National Limited itself was eliminated a month later, ending over 130 years of intercity rail service in Columbus.
Current state and legacy |
9733_18 | The freight yards and servicing facilities located east of the station had been replaced by the construction of the new Buckeye Yard near Hilliard by the Penn Central in the late 1960s. The multitrack yards and shop areas eventually gave way to I-670 in the early 1990s. The viaduct over I-670 was constructed with a cap, and shops lining High Street reminiscent of the long gone arcade.
Amtrak has not returned to Columbus since the end of the National Limited. However, as part of the Ohio Hub plan, there are plans to build a new multi-modal station on at least part of the site of the former rail terminal. It is planned to be located between the Ohio Center and the Greater Columbus Convention Center. A future streetcar or light rail line could be built on the west end of the proposed station. |
9733_19 | Proposed new station
In July 2021 the Franklin County Convention Facilities Authority contracted with LMN Architects and HNTB Engineering to conduct a site assessment and programming study of three possible Amtrak station locations at or near the Greater Columbus Convention Center.
On Greater Columbus Passenger Rail Station Study, which was released in early January 2022, details a plan for the construction of a new downtown two-level station near the intersection of High Street and Nationwide Boulevard. The proposed single platform / single track station could be built at a cost of $23 million.
See also
National Register of Historic Places listings in Columbus, Ohio
References
External links |
9733_20 | Former New York Central Railroad stations
Former Pennsylvania Railroad stations
Columbus, Ohio
Demolished railway stations in the United States
Transportation buildings and structures in Franklin County, Ohio
Union Station (Columbus, Ohio)
Former railway stations in Ohio
Railway stations on the National Register of Historic Places in Ohio
Railway stations in the United States opened in 1897
Railway stations closed in 1977
Buildings and structures demolished in 1979
Union Station (Columbus, Ohio)
Former Amtrak stations in Ohio
Former National Register of Historic Places in Ohio |
9734_0 | Tammi Reiss (born April 2, 1970) is an American actress and former professional basketball player. She is currently the coach for the University of Rhode Island. Reiss is a native of New York state. Reiss graduated from the University of Virginia in 1992 with a major in sports management. As a professional, she was chosen in the first round of the first-ever WNBA draft, and she played for two years with the Utah Starzz. |
9734_1 | Biography
Reiss was born in New York, and she attended Eldred Central School, a high-school in the area. Reiss began playing in her high-school's team as an eighth-grader. She led Eldred Central to a state championship in 1988, and finished her high school basketball career with 2,871 points scored. That total places her, as of 2014, in fifth place among New York state's all-time high school girls' scoring leaders. At Eldred Central, Reiss was coached by Ken Bjorn and Frank Kean, with boys' team coach Paul Tylawsky, a former basketball player with a Boston Celtics affiliate, also training her three times a week.
Reiss became a fan of Magic Johnson, and her dad built her a home basketball court during this period, so that she could hone her skills in a safe environment.
At Eldred, Reiss established a single-game New York state girls' basketball record by scoring 51 points in one contest. |
9734_2 | Reiss was also an accomplished runner during this period, her achievements in Track and Field including winning the state's Class D cross-country championship in 1983.
University of Virginia
Reiss received an athletic scholarship to the University of Virginia and played from 1989 to 1992. There, she teamed up with Dawn Staley and twins Heidi and Heather Burge. She was coached by Debbie Ryan. At the University of Virginia, Reiss became a three-time all American.
During her stellar college career, she was a four time all league honoree, leading her team to the NCAA Final Four three straight times while being named to the ACC women's championship all tournament squad twice, scoring 1,842 points and making 437 free throws (in both cases, placing in second place all time among women in the school's history) and scoring 139 three-point shots while making 41% of her shots from the three-point line, both of the latter all time school records for women's basketball. |
9734_3 | Reiss got interested in acting during her stint at the University of Virginia, and she took a Drama 101 class there.
After college and the WNBA
Frustrated at the lack of a women's professional basketball league in the United States, Reiss returned to her college as an assistant coach. After two years, however, the WNBA had formed and Reiss was drafted in the first round (fifth pick) by the Utah Starzz.
Reiss had been scouted by the Starzz after she received a telephone call from WNBA president Val Ackerman, who invited her to attend a veteran tryout camp where WNBA teams would observe prospect players. The Starzz were impressed by her play.
Reiss played for the Starzz during the 1997 and 1998 WNBA seasons, averaging 7.2 points, 2.7 assists and 2.3 rebounds per game.
Coaching career
Reiss became assistant coach of the Starzz in 2001 and remained with the team through 2003 (staying with the team when it relocated to San Antonio, Texas as the San Antonio Silver Stars). |
9734_4 | In 2002, Reiss was selected to the ACC's 50th anniversary women's basketball team.
In 2011, Reiss joined San Diego State University as assistant coach of the Lady Aztecs basketball team. She helped direct the team to a sweep of the Mountain West regular season and championship, as well as a spot in the NCAA championship tournament.
In 2013, Reiss joined the Cal State-Fullerton University as one of their women's basketball team's assistant coaches.
In 2015, Reiss joined the Syracuse University staff as one of their women's basketball assistant coaches.
On April 18, 2019, she was named the 9th head coach in Rhode Island Rams women's basketball history.
Acting career
Reiss debuted as an actress in a 1999 episode of the television comedy, Sister Sister (The Road Less Travelled). In 2002, she played one of the main characters, Vicki Sanchez, in the feature comedy film, Juwanna Mann. That same year, she played a coach in the made-for-television film Double Teamed. |
9734_5 | She also appeared in Love and Basketball.
Outside basketball
Reiss is an avid public speaker in the Salt Lake City, Utah area, where she became based after she was signed by the Starzz. In the 1998 off-season, Reiss joined the Utah Jazz television broadcasting team. She also has a basketball camp and owns a business named Hoop Dreams, Inc, and one named T & R Management. Reiss has also worked as a personal trainer at Gold's Gym and as operations manager for ProTech.
Head coaching record
References
External links
Rhode Island Rams bio |
9734_6 | 1970 births
Living people
Actresses from New York City
All-American college women's basketball players
American women's basketball coaches
American women's basketball players
Basketball coaches from New York (state)
Basketball players from New York City
Virginia Cavaliers women's basketball coaches
Rhode Island Rams women's basketball coaches
San Diego State Aztecs women's basketball coaches
Syracuse Orange women's basketball coaches
Utah Starzz draft picks
Utah Starzz players
Virginia Cavaliers women's basketball players |
9735_0 | Carma Hinton (, born 1949) is a documentary filmmaker and Clarence J. Robinson Professor of Visual Culture and Chinese Studies at George Mason University. She worked with Richard Gordon in directing thirteen documentary films about China, including Morning Sun and The Gate of Heavenly Peace. She has also taught at Swarthmore College, Wellesley College, MIT, and Northeastern University and has lectured on Chinese culture, history, and film around the world.
Early life
Hinton was born to American parents in Beijing, China. Her father was William H. Hinton, an American farmer and prolific writer. Hinton was raised speaking Chinese as her first language. She attended Beijing's prestigious 101 Middle School before leaving the country when she was twenty-one.
Education
Hinton attended Harvard University where she earned a Ph.D. in art history.
Career |
9735_1 | Films
Hinton has received several awards for her work in film including the George Foster Peabody Award (twice), the John E. O'Connor Film Award, the Best Social and Political Documentary and the International Critics Prize (Banff Television Festival), as well as a number of nominations for "best documentary feature". |
9735_2 | Her films have received recognition in both the popular press and in academic journals.
Morning Sun, about China's Cultural Revolution—is "a stunning new documentary film" (Newsweek), "an astonishing mix of propaganda and news footage ... an illuminating look at China's dark time" (The Boston Globe), and "transfixing" (The New York Times).
The Gate of Heavenly Peace, about the 1989 Tiananmen Square protests—"is a deep, powerful and rivetingly complex study of Tiananmen" (Newsweek), "enthralling" (The New York Times), and "one of the great documentaries of the past 20 years" (Boston Phoenix).
One Village in China—"an empathetic introduction to a handful of people who live in a complexly textured world of large power constellations, intimate social relations and deep moral dilemmas" (Journal of Asian Studies).
Long Bow Trilogy: |
9735_3 | Small Happiness—" Shows the changing lives of village women, called "invaluable for both general audiences and the academic community" (Smithsonian Institution).
To Taste 100 Herbs: Gods, Ancestors, and Medicine depicts the work of a Chinese herbal physician and his Catholic faith.
All Under Heaven |
9735_4 | Hinton's films have been shown in numerous film festivals and other venues worldwide and have been broadcast on television stations around the world.
Other work
Hinton has also produced websites for Morning Sun and The Gate of Heavenly Peace. These sites contain thousands of pages of text in Chinese and English, along with media clips, slideshows, photographs, posters, diaries, and other images. The sites receive over twenty-thousand visitors per month, and they have been incorporated into Chinese studies courses worldwide. The Gate of Heavenly Peace website has been recognized by The Washington Post, The Boston Globe, Wired, and Yahoo, among others, as one of the leading Internet resources on China. It has received an award from the Australian National University as one of the best web resources in the fields of social sciences and humanities. It is also rated as an essential educational resource by the Internet Guide for China Studies at Heidelberg University. |
9735_5 | In 1997, Hinton assisted the Peabody Essex Museum in Salem, Massachusetts, in a unique project to bring a Qing dynasty house from China's Anhui province to the U.S. The house, known as Yin Yu Tang, has been reassembled at the Peabody, where it provides an extraordinary opportunity for visitors to learn about Chinese architecture, traditional culture, and daily life.
Personal |
9735_6 | Notable family members
William Hinton (father), author of Fanshen: A Documentary of Revolution in a Chinese Village.
Bertha Sneck (mother), translator for Chinese government.
Joan Hinton (aunt), a nuclear physicist who worked on the Manhattan Project in Los Alamos, and her husband Erwin (Sid) Engst
Carmelita Hinton (grandmother), educator and founder of the Putney School in Vermont.
Charles Howard Hinton (great-grandfather), mathematician and science fiction writer.
George Boole (great-great-grandfather), mathematician and philosopher, inventor of boolean algebra.
Ethel Lilian Voynich (great-grandaunt, daughter of George Boole), novelist, musician, author of The Gadfly. Her husband, Wilfrid Michael Voynich, was an antique book-dealer and the eponym of the Voynich manuscript. Clips from a film of The Gadfly appear in Carma Hinton's 2003 documentary Morning Sun
References |
9735_7 | External links
Official Home Page at George Mason University
Morning Sun
The Gate of Heavenly Peace
"Anatomy of a Massacre," Village Voice article on The Gate of Heavenly Peace
1949 births
Harvard University alumni
American documentary filmmakers
American expatriates in China
Living people
Hinton family |
9736_0 | Clonazepam, sold under the brand Klonopin among others, is a medication used to prevent and treat seizures, panic disorder, anxiety, and the movement disorder known as akathisia. It is a tranquilizer of the benzodiazepine class. It is taken by mouth. Effects begin within one hour and last between six and twelve hours.
Common side effects include sleepiness, poor coordination, and agitation. Long-term use may result in tolerance, dependence, and withdrawal symptoms if stopped abruptly. Dependence occurs in one-third of people who take clonazepam for longer than four weeks. There is an increased risk of suicide, particularly in people who are already depressed. If used during pregnancy it may result in harm to the fetus. Clonazepam binds to GABAA receptors, thus increasing the effect of the chief inhibitory neurotransmitter γ-aminobutyric acid (GABA). |
9736_1 | Clonazepam was patented in 1960 and went on sale in 1975 in the United States from Roche. It is available as a generic medication. In 2019, it was the 46th most commonly prescribed medication in the United States, with more than 15million prescriptions. In many areas of the world it is commonly used as a recreational drug.
Medical uses
Clonazepam is prescribed for short term management of epilepsy, anxiety, and panic disorder with or without agoraphobia.
Seizures
Clonazepam, like other benzodiazepines, while being a first-line treatment for acute seizures, is not suitable for the long-term treatment of seizures due to the development of tolerance to the anticonvulsant effects. |
9736_2 | Clonazepam has been found effective in treating epilepsy in children, and the inhibition of seizure activity seemed to be achieved at low plasma levels of clonazepam. As a result, clonazepam is sometimes used for certain rare childhood epilepsies; however, it has been found to be ineffective in the control of infantile spasms. Clonazepam is mainly prescribed for the acute management of epilepsies. Clonazepam has been found to be effective in the acute control of non-convulsive status epilepticus; however, the benefits tended to be transient in many people, and the addition of phenytoin for lasting control was required in these patients.
It is also approved for treatment of typical and atypical absences (seizures), infantile myoclonic, myoclonic, and akinetic seizures. A subgroup of people with treatment resistant epilepsy may benefit from long-term use of clonazepam; the benzodiazepine clorazepate may be an alternative due to its slow onset of tolerance. |
9736_3 | Anxiety disorders
Panic disorder with or without agoraphobia.
Clonazepam has also been found effective in treating other anxiety disorders, such as social phobia, but this is an off-label use.
The effectiveness of clonazepam in the short-term treatment of panic disorder has been demonstrated in controlled clinical trials. Some long-term trials have suggested a benefit of clonazepam for up to three years without the development of tolerance but these trials were not placebo-controlled. Clonazepam is also effective in the management of acute mania. |
9736_4 | Muscle disorders
Restless legs syndrome can be treated using clonazepam as a third-line treatment option as the use of clonazepam is still investigational. Bruxism also responds to clonazepam in the short-term. Rapid eye movement sleep behavior disorder responds well to low doses of clonazepam.
The treatment of acute and chronic akathisia induced by neuroleptics, also called antipsychotics.
Spasticity related to amyotrophic lateral sclerosis.
Alcohol withdrawal syndrome |
9736_5 | Other
Benzodiazepines, such as clonazepam, are sometimes used for the treatment of mania or acute psychosis-induced aggression. In this context, benzodiazepines are given either alone, or in combination with other first-line drugs such as lithium, haloperidol or risperidone. The effectiveness of taking benzodiazepines along with antipsychotic medication is unknown, and more research is needed to determine if benzodiazepines are more effective than antipsychotics when urgent sedation is required.
Hyperekplexia
Many forms of parasomnia and other sleep disorders are treated with clonazepam.
It is not effective for preventing migraines.
Contraindications
Coma
Current alcohol use disorder
Current substance use disorder
Respiratory depression. |
9736_6 | Adverse effects
In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.
Common
Sedation
Motor impairment |
9736_7 | Less common
Confusion
Irritability and aggression
Psychomotor agitation
Lack of motivation
Loss of libido
Impaired motor function
Impaired coordination
Impaired balance
Dizziness
Cognitive impairments
Hallucinations.
Short-term memory loss
Anterograde amnesia (common with higher doses)
Some users report hangover-like symptoms of drowsiness, headaches, sluggishness, and irritability upon waking up if the medication was taken before sleep. This is likely the result of the medication's long half-life, which continues to affect the user after waking up. While benzodiazepines induce sleep, they tend to reduce the quality of sleep by suppressing or disrupting REM sleep. After regular use, rebound insomnia may occur when discontinuing clonazepam.
Benzodiazepines may cause or worsen depression.
Occasional
Dysphoria
Induction of seizures or increased frequency of seizures
Personality changes
Behavioural disturbances
Ataxia |
9736_8 | Rare
Suicide through disinhibition
Psychosis
Incontinence
Liver damage
Paradoxical behavioural disinhibition (most frequently in children, the elderly, and in persons with developmental disabilities)
Rage
Excitement
Impulsivity
The long-term effects of clonazepam can include depression, disinhibition, and sexual dysfunction.
Drowsiness
Clonazepam, like other benzodiazepines, may impair a person's ability to drive or operate machinery. The central nervous system depressing effects of the drug can be intensified by alcohol consumption, and therefore alcohol should be avoided while taking this medication. Benzodiazepines have been shown to cause dependence. Patients dependent on clonazepam should be slowly titrated off under the supervision of a qualified healthcare professional to reduce the intensity of withdrawal or rebound symptoms. |
9736_9 | Withdrawal-related
Anxiety
Irritability
Insomnia
Tremors
Headaches
Stomach pain
Nausea
Hallucinations
Suicidal thoughts or urges
Depression
Fatigue
Dizziness
Sweating
Confusion
Potential to exacerbate existing panic disorder upon discontinuation
Seizures similar to delirium tremens (with long-term use of excessive doses)
Benzodiazepines such as clonazepam can be very effective in controlling status epilepticus, but, when used for longer periods of time, some potentially serious side-effects may develop, such as interference with cognitive functions and behavior. Many individuals treated on a long-term basis develop a dependence. Physiological dependence was demonstrated by flumazenil-precipitated withdrawal. Use of alcohol or other CNS depressants while taking clonazepam greatly intensifies the effects (and side effects) of the drug.
A recurrence of symptoms of the underlying disease should be separated from withdrawal symptoms.
Tolerance and withdrawal |
9736_10 | Like all benzodiazepines, clonazepam is a GABA-positive allosteric modulator. One-third of individuals treated with benzodiazepines for longer than four weeks develop a dependence on the drug and experience a withdrawal syndrome upon dose reduction. High dosage and long-term use increase the risk and severity of dependence and withdrawal symptoms. Withdrawal seizures and psychosis can occur in severe cases of withdrawal, and anxiety and insomnia can occur in less severe cases of withdrawal. A gradual reduction in dosage reduces the severity of the benzodiazepine withdrawal syndrome. Due to the risks of tolerance and withdrawal seizures, clonazepam is generally not recommended for the long-term management of epilepsies. Increasing the dose can overcome the effects of tolerance, but tolerance to the higher dose may occur and adverse effects may intensify. The mechanism of tolerance includes receptor desensitization, down regulation, receptor decoupling, and alterations in subunit |
9736_11 | composition and in gene transcription coding. |
9736_12 | Tolerance to the anticonvulsant effects of clonazepam occurs in both animals and humans. In humans, tolerance to the anticonvulsant effects of clonazepam occurs frequently. Chronic use of benzodiazepines can lead to the development of tolerance with a decrease of benzodiazepine binding sites. The degree of tolerance is more pronounced with clonazepam than with chlordiazepoxide. In general, short-term therapy is more effective than long-term therapy with clonazepam for the treatment of epilepsy. Many studies have found that tolerance develops to the anticonvulsant properties of clonazepam with chronic use, which limits its long-term effectiveness as an anticonvulsant. |
9736_13 | Abrupt or over-rapid withdrawal from clonazepam may result in the development of the benzodiazepine withdrawal syndrome, causing psychosis characterised by dysphoric manifestations, irritability, aggressiveness, anxiety, and hallucinations. Sudden withdrawal may also induce the potentially life-threatening condition, status epilepticus. Anti-epileptic drugs, benzodiazepines such as clonazepam in particular, should be reduced in dose slowly and gradually when discontinuing the drug to mitigate withdrawal effects. Carbamazepine has been tested in the treatment of clonazepam withdrawal but was found to be ineffective in preventing clonazepam withdrawal-induced status epilepticus from occurring.
Overdose
Excess doses may result in:
Difficulty staying awake
Mental confusion
Nausea
Impaired motor functions
Impaired reflexes
Impaired coordination
Impaired balance
Dizziness
Respiratory depression
Low blood pressure
Coma |
9736_14 | Coma can be cyclic, with the individual alternating from a comatose state to a hyper-alert state of consciousness, which occurred in a four-year-old boy who suffered an overdose of clonazepam. The combination of clonazepam and certain barbiturates (for example, amobarbital), at prescribed doses has resulted in a synergistic potentiation of the effects of each drug, leading to serious respiratory depression.
Overdose symptoms may include extreme drowsiness, confusion, muscle weakness, and fainting. |
9736_15 | Detection in biological fluids
Clonazepam and 7-aminoclonazepam may be quantified in plasma, serum, or whole blood in order to monitor compliance in those receiving the drug therapeutically. Results from such tests can be used to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. Both the parent drug and 7-aminoclonazepam are unstable in biofluids, and therefore specimens should be preserved with sodium fluoride, stored at the lowest possible temperature and analyzed quickly to minimize losses. |
9736_16 | Special precautions
The elderly metabolize benzodiazepines more slowly than younger people and are also more sensitive to the effects of benzodiazepines, even at similar blood plasma levels. Doses for the elderly are recommended to be about half of that given to younger adults and are to be administered for no longer than two weeks. Long-acting benzodiazepines such as clonazepam are not generally recommended for the elderly due to the risk of drug accumulation.
The elderly are especially susceptible to increased risk of harm from motor impairments and drug accumulation side effects. Benzodiazepines also require special precaution if used by individuals that may be pregnant, alcohol- or drug-dependent, or may have comorbid psychiatric disorders. Clonazepam is generally not recommended for use in elderly people for insomnia due to its high potency relative to other benzodiazepines. |
9736_17 | Clonazepam is not recommended for use in those under 18. Use in very young children may be especially hazardous. Of anticonvulsant drugs, behavioural disturbances occur most frequently with clonazepam and phenobarbital.
Doses higher than 0.5–1 mg per day are associated with significant sedation.
Clonazepam may aggravate hepatic porphyria.
Clonazepam is not recommended for patients with chronic schizophrenia. A 1982 double-blinded, placebo-controlled study found clonazepam increases violent behavior in individuals with chronic schizophrenia.
Clonazepam has similar effectiveness to other benzodiazepines at often a lower dose. |
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