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Direct corti- cal stimulation of S1 or M1 in monkeys with Hebbian Plasticity small surface electrodes at 50 Hz or less purchase valacyclovir 1000 mg otc antiviral vitamins for herpes, com- bined with training purchase 500mg valacyclovir hiv infection through skin, would be of great interest In the 1940s valacyclovir 500mg online antiviral zona zoster, Hebb described an increase in to see if such drive alters the rate or level of synaptic strength between neurons that fire to- skills learning and sensorimotor representa- gether. In a more general sense, synaptic neuron with the firing of a presynap- however, the synaptic efficacy of motor repre- tic one. Subsequently, when a presynaptic sentations are enabled by repetitive activation neuron bursts, the postsynaptic one is more of somatosensory afferents, driven by spinal likely to fire. Whereas the active synapse segmental sensory information associated with strengthens, other unrelated synapses on the the kinematics, kinetics, and temporal features postsynaptic neuron do not. The As discussed in Chapter 3, peripheral nerve, Hebbian learning rule, then, states that con- brain, and spinal cord injury may lead to new nection weights will be increased or decreased somatosensory maps appreciated by fMRI, depending on whether presynaptic and postsy- PET, and other neuroimaging and stimulation naptic activity is correlated or uncorrelated, re- techniques. Studies suggest that this relation- ship maintains the capacity of a circuit to store new information and prevents the saturation of BASIC MECHANISMS OF connections. On the other hand, home- control and sensorimotor learning, I selectively ostatic plasticity may operate over longer time explore some of the burgeoning data at the scales and by altering postsynaptic receptor level of neurons and molecules that help ex- numbers, but still closely linked to the mech- plain remodeling of sensorimotor representa- anisms of Hebbian plasticity. The heterosy- data in humans of time-dependent plasticity naptic synapse ensures that the memory persists. A subgroup of M1 neu- in modulating Hebbian synaptic strengthening rons come to represent new and behaviorally to save an association. Whereas LTP may be relevant information by subtle changes in their critical for short-term homosynaptic Hebbian temporal patterns of firing, by more correlated plasticity, repeated heterosynaptic activity may firing, and by their firing rates. They are the most robust forms of a persistent mod- Cortical Ensemble Activity ification of synaptic transmission in response to a brief stimulus. The cascade for synaptic plas- Many experiments have shown that the selec- ticity involves the modulation of neuronal ex- tive response properties of single neurons can citability by N-methyl-D-aspartate (NMDA) change by associating inputs from other neu- receptor activation, induction by triggering rons across a narrow window in time or by ma- mechanisms for plasticity after NMDA recep- EXPERIMENTAL CASE STUDIES 1–5: Listening to Neuronal Ensembles Cortical ensemble activity can be studied during a motor learning task by listening to the activity of small groups of neurons, usually from 20 to 60 randomly chosen cells located near the tip of the in- tracerebral recording electrodes. For example, electrode recordings were made from sensorimotor stri- atal neurons of rats as they learned to correctly move through a maze by making turns when they heard a tone. These changes were found when the starting gate opened and locomotion began, at the onset of auditory cues, upon making turns to the left or right, and at the end of the maze when a reward was given. The changes in ensemble activity could also have occurred among midbrain dopaminergic neurons that will shift their responses toward the earliest in- dicator of a reward in a procedural learning task and to other primary and secondary sensorimotor re- gions. Other investigators recorded from neuronal assemblies in rat motor cortex as the animals learned a task in which they had to hold down a lever for variable times with a forepaw and release it in response to an auditory or tactile stimulus. Three measures of neuronal ensemble ac- tivity—the average firing rate, temporal patterns of firing, and correlated firing among neurons— changed as the learned skill improved and the reaction time shortened. The investigators were able to predict the outcome of single trials based upon these modifications in ensemble activity. The cascade occurs ing LTP in the motor cortex were within the both presynaptically and especially postsynap- range of the discharges of sensory cortical neu- tically. In experimental protocols, LTP is in- rons that respond to ordinary peripheral affer- duced by brief, high-frequency stimulation of ent stimulation. Although tetanic stimulation of the ventrolat- Although best studied in the hippocampus, eral nucleus of the thalamus (VL) alone did not LTP and LTD have also been demonstrated in induce LTP, the researchers produced asso- normal somatosensory, motor, and visual cor- ciative LTP in the VL when they combined VL tices. They proposed a probable nonsynaptic type of memory stor- that repeated practice of a particular move- age have been demonstrated. They hypothesized that thala- tiation has also been demonstrated in activity- mocortical circuits are initially diffuse, leading dependent corticostriatal synaptic plasticity, to excessive muscle contractions during a new which would favor the initiation of a learned movement. The strengthening of connections in the susceptibility to saturation tends to happen M1 representation for the contralateral fore- when a motor memory is in its short-term frag- limb in the rat as it learns a skilled motor task ile form, before it has progressed to a long- is achieved by LTP in excitatory synaptic trans- term, consolidated internal model for an ac- mission in the horizontal cortico-cortical con- tion. In the rat model, motor some hours after learning one task can disrupt learning compared to motor activity also led to the initial learning of a second task that reuses a significant increase in the number of synapses a similar internal model for an action. Thus, protein synthesis of AMPA recep- and declarative learning both appear to have tors appears necessary for LTP. The local cal- an initial, time-limited stage that involves re- cium increase also activates other protein ki- gions of the brain that maintain the procedural nases that may aid LTP, particularly protein or declarative memory. This shifting process may also reduce monophosphate (cAMP)-dependent protein the likelihood of saturation. These kinases help lock a synapse or cell into a set of Molecular Mechanisms specific and enduring synaptic weights. The ki- nases also participate in many other signal the details of the cellular and molecular bases transduction processes relevant to plasticity. The neurotransmitter it activates a regulatory protein for transcription acts upon both -amino-3-hydroxy-5-methyl- named cAMP response element-binding pro- 4-isoxazoleproprionic (AMPA) receptors and tein (CREB). Sodium then flows through proteins to enhance synaptic strength and gen- the AMPA receptor. Calcium cannot flow erate new dendritic synapses for learning and through the NMDA receptor because magne- memory is then turned on by CREB. Upon depo- mutation in CREB or PKA pathways would re- larization of the postsynaptic neuron, the mag- duce the persistence of declarative memory, nesium block is overcome and sodium and but initial learning, which is dependent on calcium flow into the dendritic spine of the NMDA-dependent plasticity, would be normal. The neu- Long-term potentiation induction does not re- rotrophin BDNF contributes to depolaring the quire new protein synthesis, but synthesis is postsynaptic neuron. The rise in calcium within necessary if memory storage in the hippocam- the spine initiates a cascade that triggers LTP pus CA1 field is to persist for 24 hours. Metabotropic glutamate re- move from protein to protein within a dendritic ceptors, particularly the ones in the family of spine or presynaptic terminal to phosphorylate G protein–coupled receptors, may also need to proteins and alter their function. Phosphatases, be activated for the generation of LTP in some which dephosphorylate proteins, also have an types of synapses. This cascade of induction and maintenance of LTP and in trig- events continues to be explored. It occurs at the par- of the apparently mandatory steps for signal allel fiber–Purkinje cell synapse and at the transduction occurs when calcium binds to climbing fiber synapse. Once releases glutamate onto metabotropic and this molecule autophosphorylates, it is no AMPA receptors.

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We have found that by analyzing the surface through all phases of modification buy cheap valacyclovir line hiv infection rate in new york, it is possible to establish a cell culture system in which the surface composition 208 James J cheap valacyclovir online visa antiviral kit. Hickman and geometry buy valacyclovir 500 mg with mastercard hiv infection from mosquitoes, growth medium, and cell preparation method are reproducible and defined. The ability to define these characteristics enables the fabrication and study of neuronal circuits in a controlled environment. In conjunction with our continuing patterning work, we have determined some of the possible modes of communication between cells and constructed models of simple logic circuits to test our hypothesis that sensors can be based on cell-cell communication. Patterning Neuronal Circuits the complete experimental details for the neuronal patterning and electrophysiology can be found in Ravenscroft et al. An analysis of the surface both before and after culture, as well as X-ray photo- electron spectroscopy imaging of the patterns as the laser conditions were varied, was crucial to understanding the e¤ect of di¤erent combinations of fabrication variables. Optimized high-resolution circuit patterns successfully guided the neuronal adhesion and neurite outgrowth of E18–19 hippocampal neurons in a defined serum- free medium as shown in figure 10. Neuron 2 spontaneous evoked 250 ms Neuron 1 Neuron 2 spontaneous evoked 250 ms Neuron 1 Pattern Cells obeying pattern region (a) (b) Figure 10. The top two traces are the control, and the bottom two are from the circuit pattern. Building Minimalistic Hybrid Neuroelectric Devices 209 We have successfully recorded from the patterned neurons using dual patch-clamp electrophysiology (figure 10. With the dual patch-clamp technique, we monitored the emergence of spontaneous (single-cell) and evoked (two-cell) synaptic activity for both the patterned and unpatterned (control) neuronal cultures. The electrophys- iology trace from neuron 2 represents the postsynaptic neuron, and neuron 1 the electrophysiology trace for the stimulated presynaptic neuron. No evoked electro- physiology data were obtained for day 8 hippocampal neurons on a circuit-patterned surface. These results suggest that synapses form on the pattern at di¤erent rates than in random undissociated cultures, which suggests a geometry-mediated development of synaptic events. This indicates that we may be able to control synaptic development by controlling the cell growth parameters and surface geometry. Another important issue is how to orient the neurons once they are placed in the correct position. Much like an electronic transistor, not only the construction but the orientation of the device is critical for function. Banker and Cowan (1977) showed that the longest neurite from a developing embryonic neuron would become the axon. Hickman antibody for axonal identification; and labeling with anti-MAP-2 for dendrites and the cell body. This experiment indicates that polarity can also be achieved by geo- metric means alone (Stenger et al. The accurate spatial placement of a neuronal cell network allows a wide spectrum of circuit and fabrication technology to be applied to the detection of signals trans- mitted within the network. We have also developed an electronic interface to a microelectrode chip and have successfully tested it by recording electrical activity from single unpatterned hippocampal neurons using metal microelectrodes (Jung et al. The neurons were grown on a silicon nitride (Si3N4)-coated microelectrode, and the signals were recorded from gold microelectrodes in serum-free media. This demonstrates that we can culture the cells in a defined media on the Si3N4 surface and record the signals, and that the electronic interface can process and display the electrophysiological sig- nals. The results demonstrate that the signals produced by the mammalian cells are strong enough to be picked up by the electrodes, and the signal-to-noise ratio can approach that achieved with patch-clamp electrophysiology. This result demonstrates the feasibility of using the sensor to evaluate drug candi- dates if we can establish the modes of cell-cell communication that could be moni- tored as an indicator of cell function. Modeling Cell-Cell Communication We believe that there will be di¤erent modes of operation of the system based on the number and location of synapses, which will permit the fabrication of neuroelectric devices with distinct input-output relationships. To address this question, preliminary simulations of simple two-neuron circuits were made using the neural modeling pro- gram GENESIS (Wilson et al. In these models, the interaction between an excitatory and an inhibitory neuron was simulated. For the sake of simplicity, both current injection and voltage mea- surements were performed at the soma of each neuron, as represented by the micro- electrodes in figure 10. We typically ran the modeling experiments using current injection on both neurons. Building Minimalistic Hybrid Neuroelectric Devices 211 current voltage injection measurement electrode electrode I I 1 2 pA Neuron 1 pA Neuron 2 Current Current 400 400 0 0 100 200 300 400 msec 100 200 300 400 msec Figure 10. A B input A +5V input B V out I + E Vin output Dual Neuron Circuit Corresponding Transistor "Inverter" Circuit Equivalent Key: : stimulationsite : recording site : synapse I: inhibitory neuron E: excitatory neuron Figure 10. With appropriately chosen stimuli, this simple circuit can produce distinctive behavior, as demonstrated by the simulation e¤orts in figure 10. For example, a constant stimulation train ap- plied at input B would be gated based on the state of input A. Stimulation of input A would inhibit the transmission of excitation, whereas the lack of stimulation of input A would permit the propagation of excitability. The behavior of this circuit model is similar to that of a simple transistor-logic circuit where the state of the transistor gate influences circuit output (figure 10. Furthermore, this circuit model is the core element of a circuit to explain directional selectivity in the mammalian retina 212 James J.

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Drugs that decrease effects of azithromycin: (1) Antacids Antacids decrease peak serum levels (continued) 558 SECTION 6 DRUGS USED TO TREAT INFECTIONS NURSING ACTIONS RATIONALE/EXPLANATION e. Drugs that decrease effects of chloramphenicol: (1) Enzyme inducers (eg, rifampin) Reduce serum levels, probably by accelerating liver metabolism of chloramphenicol f. Drugs that decrease effects of clindamycin: (1) Erythromycin Delays absorption (2) Kaolin-pectin g. Drug that increases effects of metronidazole: (1) Cimetidine Inhibits hepatic metabolism of metronidazole h. Drugs that decrease effects of metronidazole: (1) Enzyme inducers (phenobarbital, phenytoin, prednisone, These drugs induce hepatic enzymes and decrease effects of rifampin) metronidazole by accelerating its rate of hepatic metabolism. How would you recognize pseudomembranous colitis in Answer: This error occurred because the drug infused too rapidly. What would you do if you thought a client might Although the IV rate was calculated correctly, the IV could have have it? Why is metronidazole preferred over vancomycin for ini- use an IV controller pump to regulate the infusion rate. Which antibacterial drug is considered the drug of choice but is caused by histamine release and vasodilation when infusion for MRSA and SSNA? What is red man syndrome, and how can it be prevented premedication with an antihistamine. What is the main clinical importance of the newer drugs, linezolid and quinupristin/dalfopristin? Nursing Notes: Apply Your Knowledge SELECTED REFERENCES Answer: Diarrhea is a side effect of many antibiotics. Antimicrobial agents: Protein synthesis inhibitors arrhea is severe, it is important to determine if the cause is and miscellaneous antibacterial agents. Limbird pseudomembranous colitis, which is caused when antibiotics (Eds. The drug-resistant pneumococcus: this is often associated with the use of clindamycin. Hospital Infection Control Practices Advisory Committee (HICPAC) Treatment includes metronidazole (Flagyl) or oral vancomycin. What are adverse effects with erythromycin, and how may they be prevented or minimized? Discuss ways to increase adherence to anti- drug-resistant tuberculosis infections. Describe factors affecting the use of primary, implications of using primary antitubercular secondary, and other drugs in the treatment of drugs. Critical Thinking Scenario John Phillips, a homeless person with a history of drug and alcohol abuse, comes to the emergency depart- ment with a productive cough, complaints of night sweats, and fatigue. The physician suspects tuberculosis (TB) and orders a purified protein derivative (PPD) skin test, chest x-ray, and sputum for acid-fast bacilli. Reflect on: the necessary infection control measures to use before TB is confirmed or ruled out. Factors that affect compliance with drug treatment for John Phillips and a plan to improve and monitor compliance. Phillips will require drug treatment, and how you can evaluate when the TB is cured. OVERVIEW Tuberculosis commonly occurs in many parts of the world and causes many deaths annually. In the United Tuberculosis (TB) is an infectious disease that usually affects States, active disease has waned to a historical low level. It is caused by Mycobac- include increased exposure during a resurgence of active terium tuberculosis, the tubercle bacillus. In general, these disease between 1985 and 1992, immigration from coun- bacilli multiply slowly; they may lie dormant in the body for tries where the disease is common, and increasing numbers many years; they resist phagocytosis and survive in phagocytic of people with conditions or medications that depress the cells; and they develop resistance to antitubercular drugs. The bacteria be- come inactive, but they remain alive in the body and There are four distinct phases in the initiation and progres- can become active later. Transmission occurs when an uninfected person in- not spread TB to others, usually have a positive skin hales infected airborne particles that are exhaled by an test reaction, and can develop active TB disease years infected person. Major factors affecting transmission later if the latent infection is not effectively treated. In are the number of bacteria expelled by the infected per- many people with LTBI, the infection remains inactive son and the closeness and duration of the contact be- throughout their lives. In others, the TB bacteria be- tween the infected and the uninfected person. About 6 to 8 weeks after exposure, those latent infection, although new infection can also occur. Both reactivated and new infections are more likely to Within approximately 6 months of exposure, sponta- occur in people whose immune systems are depressed neous healing occurs as the bacilli are encapsulated in by disease (eg, human immunodeficiency virus [HIV] in- calcified tubercles. Among people with who become infected with TB bacteria, the immune LTBI, signs and symptoms of active disease (eg, cough Transmission Primary tuberculosis Latent tuberculosis "Reactivation" tuberculosis Progression after 2 years, 5% Skin-test Spontaneous conversion in healing in Progression 6 to 8 weeks 6 months within 2 years, 5% Progression with concurrent HIV infection, 10% each year Figure 38–1 Transmission of Tuberculosis and Progression from Latent Infection to Reactivated Disease. Among persons who are seronegative for the human immunodeficiency virus (HIV), approximately 30 percent of heavily exposed persons will become infected.

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His physi- cians suggested that he see the only neurosurgeon in the county cost of valacyclovir antiviral blog. Despite his health emergency purchase 1000mg valacyclovir visa hiv infection during menstruation, he was not able to make an appointment to see this neurosurgeon for more than 10 weeks order valacyclovir 1000 mg hiv infection rate in india. In pain and unable to walk because of progressively worsening foot drop and muscle weakness, he sought the help of a physician friend. This friend referred him to a brash, iconoclastic Harvard-trained neurologist, who, in turn, referred him to a virtuoso neurosurgeon at a county hospital 100 miles away. After only 20 minutes with this neurosurgeon, he was rushed to the operating room and underwent a nine-hour emergency procedure. He was later told by the neurosurgeon that he would have been a paraplegic or died if he had not received the operation that day. Postoperative care was sub- optimal, as he had to travel 100 miles to see the surgeon for follow-up. Eventually, this surgeon chose to travel to a more centralized location twice per month to accommodate his patients in outlying areas. Roberts states that we need to overcome petty bureaucracies that do not allow matching of supply with demand. The ready availability of quality care needs to be patient driven and closely monitored by a third party that does not have a vested interest in the market. Roberts is concerned about the status of continuing medical educa- tion. He guesses that it is probably easy for physicians in large, urban teach- ing hospitals to keep abreast of the latest diagnostic and therapeutic advances. The system does not necessarily encourage physicians to keep up to date. This lack of current, in-depth knowledge is particularly important as sup- ply-demand issues force consumers to seek care in instant med clinics. On many occasions, he has gone to the emergency room for an emergency and had to wait four to five hours before being treated. This experience is unpleasant and forces people to seek alternative sites of care that may not provide the best care for complex, chronically ill patients. Roberts also feels that we need to learn from our errors as well as successes. We should require that groups of physicians regularly review cases and learn how to deliver care in a better way. This analysis needs to occur internally within an institution as well as externally across institu- tions. Ideally, the analysis would directly involve patients and families to gain their perspectives. In addition, the learning should be contextual: we should not only learn how to do better the next time but also know if what 22 the Healthcare Quality Book we are doing makes sense within our overall economic, epidemiological, and societal context. This knowledge comes not only from science but also from analy- sis of mistakes that occur in the process of delivering care. Patients need to be involved in the collection and synthesis of these data. The transfer of knowledge among patients, scientists, and practitioners needs to be empha- sized and simplified. Roberts has been very impressed with the quality of care given by peo- ple other than physicians, and he believes that the growth of alternative healthcare provider models has been a definite advance in the system. Roberts cites the effectiveness of his physical therapists as healthcare providers; they are alert, patient conscious, conscientious, and respectful. In addition, these providers are careful to maintain close communication with physicians. Now, after three days, he is discharged to a rehabilitation facility that is better equipped to help him recuperate and return to full functioning. Roberts knows how crucial his family and friends are in his med- ical care. Without their support, recommendations, constant questioning, and advocacy, his condition would be more precarious. Conclusion the previous sections provide a brief insight into some successful improve- ment projects; it would be even easier to find examples of failures and the subsequent lessons learned. The main message is that, although the information on the gap between current practice and best practice may be daunting, improvement is occurring, albeit in pockets, and the oppor- tunity is before us to continue to make quality a necessity, not just a nicety, in healthcare. The aim of this textbook is to provide a comprehensive overview of the critical components of the healthcare quality landscape. You, as read- ers and leaders, should use this text as a resource and framework for under- Healthcare Quality and the Patient 23 standing the connectivity of multiple aspects of healthcare quality from the science base, patient perspective, organizational implications, and envi- ronmental effects. This chapter, specifically, sets the stage by highlighting • the current state of healthcare quality; • the importance of the patient in goals and results; • Promising evidence of the great capacity for significant improve- ment in systems of care; • Examples of breakthrough improvements happening today; and • the call to action for all healthcare stakeholders to continue to rethink and redesign our systems for better health for all. Building on this chapter, the book will outline healthcare quality similar to the levels of the healthcare system outlined by IOM. Identify five ways in which you can put the patient more in control of his or her care. Think of an experience you have had with healthcare or one of your family or friends.

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Draw the hands into your body order valacyclovir american express hiv infection rate in egypt, tucking the elbows into your ribs cheap 500mg valacyclovir with mastercard hiv infection likelihood, and Cat Step out to the right position order valacyclovir online now hiv infection rate pattaya. As your weight shifts forward, push out with both hands over your right leg. Make sure not to push so far that your back bends and your bottom juts out—your hands should push no further than your right foot. Remember that at this point, your rear foot is flat and your back is straight. Now, as you begin to bring your left foot up next to your right foot, draw the hands into the body again. One way to remember the proper breathing is to think of the martial meaning of the movements. So, when you are Warding Off, or pushing someone away, you are exerting yourself and need to exhale. When you are beginning to step and are draw- ing your feet together, or are coiling your arm across your body, you are in a defen- sive mode, so you would then inhale. Before you lift the bag, you get your hands into position underneath it, place your feet directly under your body, and inhale. Then when you actually start lifting, you exhale, straightening up your back and bringing the bag of groceries close to your body to maintain your center of gravity. If you were to reverse this breathing cycle, you would find that you are not as comfortable with the weight being lifted, or that you could not lift it at all. This follows the basic breathing principles of weight lifting: you inhale before you put forth your effort, and then exhale as you lift. So whether you are Warding Off, Holding a Ball, or Pushing With Both Hands, you should exhale on the actual application or performance of the move, and in- hale during the transitions or in-between times. This chapter will outline the pros and cons of such modifications, along with step-by-step instructions for the seated movements. But you can still breathe diaphragmatically, still work the arms, shoulders, wrists, and even, to an extent, the waist. You still reap the benefits of energy flow through the upper body and arms and, to a limited degree, the legs. A basic sitting position involves the feet being placed flat on the floor. If you have short legs or a large chair, try to find a comfortable, yet supportive and firm chair to sit in. The ideal chair would be a wooden dining table–type chair, with no arms and a fairly straight back. The Chinese have a saying: the back of a chair is only for hanging your coat. The hands will be returning to a neutral position after most of the exercises. But in seated position, you can simply let the hands rest on the knees or thighs. Opening the Chest: Same as standing version except the hands return to the knees. Painting the Rainbow: Here we need to make a slightly different type of adjust- ment. Because in the standing version we turn our feet, hips, and waist in the direction we are painting, we need to try to duplicate that as much as possible. After your opening moves, you should be sitting upright with your arms out to your sides, palms up. When you paint with one or the other hand, turn your waist in the direction of the painting stroke as much as possible, without straining. Then simply let the hands return to your lap, and start over on the opposite side. Parting the Clouds: Same as standing except, when the hands come down to your sides, bring them inward and over your lap. Whirling Arms on Horseback: Here you need to be careful not to tilt or tip in your chair. You will find, though, that if your chair has armrests, this movement can be rather difficult. Holding a Ball at Shoulder Level: Hopefully your arm can reach at least a little ways behind the chair. Gazing at the Moon Over the Shoulder: Same as standing version except, of course, the hands glide over your lap instead of hanging all the way down in front of you. Scoop the Sea and Look to the Sky: Lean forward as far as comfortable (without falling out of the chair! Set the Waves Rolling: Same as standing without shifting the weight back and forth. Punching From a Horseback Riding Stance: Same as standing; try placing your feet farther apart on the floor, but keep them parallel. Turn the waist as much as comfortable in time with the arm rotations, gliding the hands over the lap at the bottom of the rotation. Double Hands Hold Up the Heavens: Same as standing version, except the hands come down to the lap at the end of the movement.