Irregular warfare must combine good medicine, with both good tactics and good strategies: Position paper by the French Special Operations Forces Medical Command.

INTRODUCTION: Military operations are no longer limited to the application of counterterrorism and counterinsurgency strategies; they are now characterized by hybrid, irregular, and unconventional features. While some authors have indicated the need for medical support to adapt to these new modes of military operations, they have focused mainly on the tactical level of care on the battlefield. As Sun Tzu states, "Strategy without tactics is the slowest route to victory. Tactics without strategy is the noise before defeat," further proposals are still needed on the application of both medical tactics and medical strategies in irregular warfare. METHODS: Medical experts from the French Special Operations Forces (SOF) Medical Command have identified specific medical challenges that special operations face in the context of the current transformation of armed confrontations into irregular warfare. RESULTS: This position paper presents original tactical medical proposals for improving medical support in irregular warfare, ranging from the definition of a Primary-Alternate-Contingency-Emergency medical plan to the promotion of telemedical support. Original strategic medical proposals have highlighted the importance of recognizing medical issues in irregular warfare, including the medical actions carried out through and with local partners and the multiple approaches to countering medical threats. CONCLUSION: The SOF medical community must be closely involved with and facilitate the responses to the shift to irregular warfare. International collaboration and interoperability are more necessary than ever, as they will enable a more effective combination of good medicine with both good tactics and good strategies. These perspectives can also be extended to improve medical care in the conventional armed forces and austere civilian settings. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.

Combat Casualties Treated With Intranasal Ketamine for Prehospital Analgesia: A Case Series.

Optimal pain management is challenging in Tactical Combat Casualty Care (TCCC), particularly in remote and austere settings. In these situations, appropriate treatment for prehospital analgesia can be limited or delayed due to the lack of intravenous access. Several guidelines suggest to implement intranasal (IN) analgesia in French Armed Forces for forward combat casualty care (Sauvetage au Combat), similar to the US TCCC. Four medical teams from the French Medical Military Service were deployed to the Middle East and Sahel from August 2017 to March 2019 and used IN ketamine for analgesia in 76 trauma patients, out of a total of 259 treated casualties. IN administration of ketamine 50mg appeared to be safe and effective, alone or in addition to other opioid analgesics. It also had minimal side effects and led to a reduction in the doses of ketamine and morphine used by the intravenous (IV) route. The French Military Medical Service supports current developments for personal devices delivering individual doses of IN ketamine. However, further studies are needed to analyze its efficacy and safety in combat zones.

Turning the body into a clock: Accurate timing is facilitated by simple stereotyped interactions with the environment.

How animals adapt their behavior according to regular time intervals between events is not well understood, especially when intervals last several seconds. One possibility is that animals use disembodied internal neuronal representations of time to decide when to initiate a given action at the end of an interval. However, animals rarely remain immobile during time intervals but tend to perform stereotyped behaviors, raising the possibility that motor routines improve timing accuracy. To test this possibility, we used a task in which rats, freely moving on a motorized treadmill, could obtain a reward if they approached it after a fixed interval. Most animals took advantage of the treadmill length and its moving direction to develop, by trial-and-error, the same motor routine whose execution resulted in the precise timing of their reward approaches. Noticeably, when proficient animals did not follow this routine, their temporal accuracy decreased. Then, naïve animals were trained in modified versions of the task designed to prevent the development of this routine. Compared to rats trained in the first protocol, these animals didn't reach a comparable level of timing accuracy. Altogether, our results indicate that timing accuracy in rats is improved when the environment affords cues that animals can incorporate into motor routines.

No Discrete Start/Stop Signals in the Dorsal Striatum of Mice Performing a Learned Action.

A popular hypothesis is that the dorsal striatum generates discrete "traffic light" signals that initiate, maintain, and terminate the execution of learned actions. Alternatively, the striatum may continuously monitor the dynamics of movements associated with action execution by processing inputs from somatosensory and motor cortices. Here, we recorded the activity of striatal neurons in mice performing a run-and-stop task and characterized the diversity of firing rate modulations relative to run performance (tuning curves) across neurons. We found that the tuning curves could not be statistically clustered in discrete functional groups (start or stop neurons). Rather, their shape varied continuously according to the movement dynamics of the task. Moreover, striatal spiking activity correlated with running speed on a run-by-run basis and was modulated by task-related non-locomotor movements, such as licking. We hypothesize that such moment-to-moment movement monitoring by the dorsal striatum contributes to the learning of adaptive actions and/or updating their kinematics.

A Serious Game for Massive Training and Assessment of French Soldiers Involved in Forward Combat Casualty Care (3D-SC1): Development and Deployment.

BACKGROUND: The French Military Health Service has standardized its military prehospital care policy in a ''Sauvetage au Combat'' (SC) program (Forward Combat Casualty Care). A major part of the SC training program relies on simulations, which are challenging and costly when dealing with more than 80,000 soldiers. In 2014, the French Military Health Service decided to develop and deploy 3D-SC1, a serious game (SG) intended to train and assess soldiers managing the early steps of SC. OBJECTIVES: The purpose of this paper is to describe the creation and production of 3D-SC1 and to present its deployment. METHODS: A group of 10 experts and the Paris Descartes University Medical Simulation Department spin-off, Medusims, coproduced 3D-SC1. Medusims are virtual medical experiences using 3D real-time videogame technology (creation of an environment and avatars in different scenarios) designed for educational purposes (training and assessment) to simulate medical situations. These virtual situations have been created based on real cases and tested on mannequins by experts. Trainees are asked to manage specific situations according to best practices recommended by SC, and receive a score and a personalized feedback regarding their performance. RESULTS: The scenario simulated in the SG is an attack on a patrol of 3 soldiers with an improvised explosive device explosion as a result of which one soldier dies, one soldier is slightly stunned, and the third soldier experiences a leg amputation and other injuries. This scenario was first tested with mannequins in military simulation centers, before being transformed into a virtual 3D real-time scenario using a multi-support, multi-operating system platform, Unity. Processes of gamification and scoring were applied, with 2 levels of difficulty. A personalized debriefing was integrated at the end of the simulations. The design and production of the SG took 9 months. The deployment, performed in 3 months, has reached 84 of 96 (88%) French Army units, with a total of 818 hours of connection in the first 3 months. CONCLUSIONS: The development of 3D-SC1 involved a collaborative platform with interdisciplinary actors from the French Health Service, a university, and videogame industry. Training each French soldier with simulation exercises and mannequins is challenging and costly. Implementation of SGs into the training program could offer a unique opportunity at a lower cost to improve training and subsequently the real-time performance of soldiers when managing combat casualties; ideally, these should be combined with physical simulations.

Surgical challenges in a new theater of modern warfare: The French role 2 in Gao, Mali.

INTRODUCTION: On January 11th 2013, France launched Operation Serval in Mali following Resolution 2085 of the Security Council of the United Nations. Between January and March 2013, more than 4000 French soldiers were deployed to support the Malian National Army and the African Armed Forces. METHODS: All of the patients who had surgery during Operation Serval were entered into a computerised database. Patients' demographic data (age, sex, status) and types of performed surgical procedures (specialties, injury mechanisms) were recorded. RESULTS: 268 patients were operated on in Gao's Role 2 with a total of 296 surgeries. Among those operated on, 40% were Malian civilians, 24% were French soldiers, and 36% were soldiers of the International Coalition Forces. The majority of the surgeries were orthopaedic, and visceral surgeries were common as well, representing 43% of the total surgeries. Specialised surgical procedures including neurosurgery, thoracic, and vascular surgery were also performed. Forty percent of the surgeries were scheduled. War-related traumatic surgeries represented 22% of the surgical procedures, with non-war related surgeries and non-trauma emergency surgeries making up the rest. CONCLUSION: this analysis confirms the specific characteristic of asymmetric warfare that it results in a relatively reduced number of war-related casualties. Forward surgical teams have to deal with a wide range of injuries requiring several surgical specialties. Surgeries dedicated to medical aid provided to the population also represented an important part of the surgical activity. Because of the diversity and the technicality of the surgical procedures in Role 2, surgeons had to be trained in war surgery covering all of the surgical specialties, while they maintained their specific skills. In France in 2007, the French Military Health Service Academy (École du Val-de-Grâce, Paris, France) offered an advanced course in surgery for deployment in combat zones, with a special focus on damage control surgeries and the management of mass casualties incidents.

Initial deployment of the 14th Parachutist Forward Surgical Team at the beginning of the operation Sangaris in Central African Republic.

As part of the operation Sangaris begun in December 2013 in the Central African Republic, the 14th Parachutist Forward Surgical Team (FST) was deployed to support French troops. The FST (role 2 in the NATO classification) is a mobile surgical-medical treatment facility. The main goal of the FST is to assure the initial damage control surgery and resuscitation for combat casualties, allowing for the early evacuation to combat support hospitals (roles 3 or 4), where further treatments are completed. During the first trimester of the operation Sangaris, 42 patients were treated at FST, of whom 29 underwent surgery. Almost 50% of patients operated on were French servicemen. All admissions were emergency admissions. Orthopedic surgery represented two-thirds of surgical interventions executed as a result of the high proportion of limb injuries. Fifty percent of injuries were specifically linked to combat. Surgery in an FST is primarily dedicated to the treatment of combat casualties with hemorrhagic injuries, but additionally plays a part in supporting general medical care of French troops. Medical aid to the general civilian population is justifiable because of the presence of medical treatment facilities, even in the initial implementation of a military operation.

Normotopic cortex is the major contributor to epilepsy in experimental double cortex.

OBJECTIVE: Subcortical band heterotopia (SBH) is a cortical malformation formed when neocortical neurons prematurely stop their migration in the white matter, forming a heterotopic band below the normotopic cortex, and is generally associated with intractable epilepsy. Although it is clear that the band heterotopia and the overlying cortex both contribute to creating an abnormal circuit prone to generate epileptic discharges, it is less understood which part of this circuitry is the most critical. Here, we sought to identify the origin of epileptiform activity in a targeted genetic model of SBH in rats. METHODS: Rats with SBH (Dcx-KD rats) were generated by knocking down the Dcx gene using shRNA vectors transfected into neocortical progenitors of rat embryos. Origin, spatial extent, and laminar profile of bicuculline-induced interictal-like activity on neocortical slices were analyzed by using extracellular recordings from 60-channel microelectrode arrays. Susceptibility to pentylenetetrazole-induced seizures was assessed by electrocorticography in head-restrained nonanesthetized rats. RESULTS: We show that the band heterotopia does not constitute a primary origin for interictal-like epileptiform activity in vitro and is dispensable for generating induced seizures in vivo. Furthermore, we report that most interictal-like discharges originating in the overlying cortex secondarily propagate to the band heterotopia. Importantly, we found that in vivo suppression of neuronal excitability in SBH does not alter the higher propensity of Dcx-KD rats to display seizures. INTERPRETATION: These results suggest a major role of the normotopic cortex over the band heterotopia in generating interictal epileptiform activity and seizures in brains with SBH.

Pioneer glutamatergic cells develop into a morpho-functionally distinct population in the juvenile CA3 hippocampus.

The developing CA3 hippocampus is comprised by highly connected hub neurons that are particularly effective in achieving network synchronization. Functional hub neurons were shown to be exclusively GABAergic, suggesting that the contribution of glutamatergic neurons to physiological synchronization processes at early postnatal stages is minimal. However, without fast GABAergic transmission, a different situation may prevail. In the adult CA3, blocking fast GABAergic transmission induces the generation of network bursts that can be triggered by the stimulation of single pyramidal neurons. Here we revisit the network function of CA3 glutamatergic neurons from a developmental viewpoint, without fast GABAergic transmission. We uncover a sub-population of early-generated glutamatergic neurons that impacts network dynamics when stimulated in the juvenile hippocampus. Additionally, this population displays characteristic morpho-physiological features in the juvenile and adult hippocampus. Therefore, the apparently homogeneous glutamatergic cell population likely displays a morpho-functional diversity rooted in temporal embryonic origins.

Improving Grubbs' II type ruthenium catalysts by appropriately modifying the N-heterocyclic carbene ligand.

The introduction of N-heterocyclic carbene ligands that incorporate correctly substituted naphthyl side chains leads to increased activity and stability in second generation ruthenium metathesis catalysts.

Impact of NHC ligand conformation and solvent concentration on the ruthenium-catalyzed ring-closing metathesis reaction.

Two saturated N-heterocyclic carbene ligands with substituted naphthyl side chains were used for the preparation of Blechert-type ruthenium metathesis precatalysts. The resulting conformers of the complexes were separated and unambiguously assigned by X-ray diffraction studies. All new complexes were compared in terms of activity to the original, SIMes-derived Blechert catalyst and were shown to be superior. A study on the impact of solvent concentration in RCM reactions using the most active of these new catalysts ultimately led to the ring closing of a variety of substrates at very low catalyst loadings.