text:
#ifndef _FXREQUESTBASE_H_
#define _FXREQUESTBASE_H_

#include "FxRequestCallbacks.hpp"

//
// COMPLETED - set when the request's i/o completion routine has executed
//
// PENDED - set when the request has been put onto the target's CSQ
//
// TIMER_SET - set when a timer has been queued along with sending the request
//             down to the target
//
// CANCELLED_FROM_TIME - set by the timer to indicate that the request was
//                       cancelled by the timer DPC
//
// IGNORE_STATE - set when the request is going to be sent ignoring the
//                state of the target.
//
enum FxRequestTargetFlags {
    FX_REQUEST_COMPLETED                = 0x01,
    FX_REQUEST_PENDED                   = 0x02,
    FX_REQUEST_TIMER_SET                = 0x04,
    FX_REQUEST_CANCELLED_FROM_TIMER     = 0x08,
    FX_REQUEST_IGNORE_STATE             = 0x10,
};

//
// internal private constraints
//
#define WDF_REQUEST_SEND_INTERNAL_OPTION_FAIL_ON_PEND (0x80000000)

#define WDF_REQUEST_INTERNAL_CONSTRAINTS_VALID_FLAGS \
    (WDF_REQUEST_SEND_INTERNAL_OPTION_FAIL_ON_PEND)

//
// Completion event callback prototype
//
typedef
VOID
(*PFN_COMPLETE_COPY_ROUTINE)(
    __in FxIoTarget* This,
    __in FxRequest* Request,
    __in_opt FxRequestContext* Context
    );

struct FxRequestTimer : public FxStump {
    MxTimer Timer;
};

enum FxRequestAllocationSource {
    REQUEST_ALLOCATED_FROM_IO = 0,  // Irp came from the I/O package
    REQUEST_ALLOCATED_INTERNAL = 1, // Irp was allocated internally and should be freed by the request
    REQUEST_ALLOCATED_DRIVER = 2,   // Irp was given to the request by the driver writer
};

enum FxRequestIrpOwnership {
    FxRequestOwnsIrp = 1,
    FxRequestDoesNotOwnIrp,
};

// begin_wpp config
// CUSTOM_TYPE(FxRequestIrpOwnership, ItemEnum(FxRequestIrpOwnership));
// end_wpp

enum FxRequestConstructorCaller {
    FxRequestConstructorCallerIsFx = 1,
    FxRequestConstructorCallerIsDriver,
};

//
// These defines are for VerifierFlags
//
enum FxRequestVerifierFlags {
    // Request has been passed to the Driver
    FXREQUEST_FLAG_DRIVER_OWNED             = 0x0001,

    // Request was returned as a "Tag" request to WdfIoQueuePeekNextRequest.
    FXREQUEST_FLAG_TAG_REQUEST              = 0x0002,

    // Request has been forwarded from one queue to another
    FXREQUEST_FLAG_FORWARDED                = 0x0004,

    // Request is being EvtIoDefault to the driver
    FXREQUEST_FLAG_DRIVER_DISPATCH          = 0x0008,

    // The driver has specified the request as cancelable
    FXREQUEST_FLAG_DRIVER_CANCELABLE        = 0x0010,

    FXREQUEST_FLAG_DRIVER_INPROCESS_CONTEXT = 0x0020,

    // The request has been cancelled
    FXREQUEST_FLAG_CANCELLED                = 0x0040,

    // the next stack location has been formatted
    FXREQUEST_FLAG_FORMATTED                = 0x0080,

    // the request has been sent on an I/O target and is in the target's sent list
    FXREQUEST_FLAG_SENT_TO_TARGET           = 0x0100,

    // used to make sure the driver stop acknowledges in the context of EvtIoStop
    FXREQUEST_FLAG_DRIVER_IN_EVTIOSTOP_CONTEXT = 0x0200,

    // used to indicate whether the Reserved Request is in use or on Free list
    FXREQUEST_FLAG_RESERVED_REQUEST_ASSOCIATED_WITH_IRP = 0x0400,
};

enum FxRequestBaseFlags {
    FxRequestBaseSystemMdlMapped  = 0x1,
    FxRequestBaseOutputMdlMapped  = 0x2,
    FxRequestBaseSyncCleanupContext = 0x10,
};

enum FxRequestBaseStaticFlags {
    FxRequestBaseStaticSystemBufferValid  = 0x1,
    FxRequestBaseStaticOutputBufferValid  = 0x2,
};

//
// Designed to fit into a byte.  FxRequestCompletionPkgFlag is a bit value
// used to distinguish between calling back into the io package or the current
// queue.  When calling back into the current queue, we assume m_IoQueue is valid
//
enum FxRequestCompletionState {
    FxRequestCompletionStateIoPkgFlag = 0x80,

    FxRequestCompletionStateNone  = 0x00,
    FxRequestCompletionStateQueue = 0x01,
    FxRequestCompletionStateIoPkg = 0x02 | FxRequestCompletionStateIoPkgFlag,
};

class FxRequestBase : public FxNonPagedObject {

    friend FxIoTarget;
    friend FxSyncRequest;

public:

    FORCEINLINE
    VOID
    SetCompletionRoutine(
        __in_opt PFN_WDF_REQUEST_COMPLETION_ROUTINE CompletionRoutine = NULL,
        __in_opt WDFCONTEXT CompletionContext = NULL
        )
    {
        m_CompletionRoutine.m_Completion = CompletionRoutine;
        m_TargetCompletionContext = CompletionContext;
    }

    PFN_WDF_REQUEST_COMPLETION_ROUTINE
    ClearCompletionRoutine(
        VOID
        )
    {
        PFN_WDF_REQUEST_COMPLETION_ROUTINE pRoutine;

        pRoutine = m_CompletionRoutine.m_Completion;
        m_CompletionRoutine.m_Completion = NULL;

        return pRoutine;
    }

    WDFCONTEXT
    ClearCompletionContext(
        VOID
        )
    {
        WDFCONTEXT pContext;

        pContext = m_TargetCompletionContext;
        m_TargetCompletionContext = NULL;

        return pContext;
    }

    FORCEINLINE
    BOOLEAN
    IsCompletionRoutineSet(
        VOID
        )
    {
        return (m_CompletionRoutine.m_Completion != NULL) ?
                    TRUE : FALSE;
    }

    FORCEINLINE
    BOOLEAN
    IsCancelRoutineSet(
        VOID
        )
    {
        return (m_CancelRoutine.m_Cancel != NULL) ?
                    TRUE : FALSE;
    }

    FORCEINLINE
    FxRequestContext*
    GetContext(
        VOID
        )
    {
        return m_RequestContext;
    }

    FORCEINLINE
    VOID
    SetContext(
        __in FxRequestContext* RequestContext = NULL
        )
    {
        //
        // If we are setting to the same value, just return
        //
        if (m_RequestContext == RequestContext) {
            return;
        }

        //
        // If we are changing the context to another unique pointer, free the
        // old context.
        //
        if (m_RequestContext != NULL) {
            delete m_RequestContext;
        }

        m_RequestContext = RequestContext;
    }

    VOID
    ContextReleaseAndRestore(
        VOID
        )
    {
        //
        // This does not free the context, rather it tells the context to release
        // any references it is holding and restore fields back into the PIRP
        //
        if (m_RequestContext != NULL && m_Irp.GetIrp() != NULL) {
            m_RequestContext->ReleaseAndRestore(this);
            VerifierClearFormatted();
        }
    }

    FORCEINLINE
    VOID
    EnableContextDisposeNotification(
        VOID
        )
    {
        MarkDisposeOverride();
    }

    FORCEINLINE
    BOOLEAN
    HasContextType(
        __in FX_REQUEST_CONTEXT_TYPE Type
        )
    {
        return (m_RequestContext != NULL &&
                m_RequestContext->m_RequestType == Type) ? TRUE : FALSE;
    }

    FORCEINLINE
    HasContext(
        VOID
        )
    {
        return (m_RequestContext != NULL &&
                m_RequestContext->m_RequestType !=
                    FX_REQUEST_CONTEXT_TYPE_NONE) ? TRUE : FALSE;
    }

    FORCEINLINE
    MdIrp
    GetSubmitIrp(
        VOID
        )
    {
        return m_Irp.GetIrp();
    }

    FORCEINLINE
    FxIrp*
    GetSubmitFxIrp(
        VOID
        )
    {
        return &m_Irp;
    }

    MdIrp
    SetSubmitIrp(
        __in_opt MdIrp NewIrp,
        __in BOOLEAN FreeIrp = TRUE
        );

    FORCEINLINE
    BOOLEAN
    CanComplete(
        VOID
        )
    {
        LONG count;
        count = InterlockedDecrement(&m_IrpCompletionReferenceCount);
        ASSERT(count >= 0);
        return count == 0 ? TRUE : FALSE;
    }

    VOID
    CompleteSubmitted(
        VOID
        );

    _Must_inspect_result_
    NTSTATUS
    ValidateTarget(
        __in FxIoTarget* Target
        );

    FORCEINLINE
    FxIoTarget*
    GetTarget(
        VOID
        )
    {
        return m_Target;
    }

    VOID
    FORCEINLINE
    SetTarget(
        __in FxIoTarget* Target
        )
    {
        m_Target = Target;
    }

    FORCEINLINE
    UCHAR
    GetTargetFlags(
        VOID
        )
    {
        // Assumes caller is holding appropriate lock
        return m_TargetFlags;
    }

    FORCEINLINE
    VOID
    SetTargetFlags(
        __in UCHAR Flags
        )
    {
        // Assumes caller is holding appropriate lock
        m_TargetFlags |= Flags;
    }

    FORCEINLINE
    ULONG
    ClearTargetFlags(
        __in UCHAR Flags
        )
    {
        ULONG oldFlags;

        oldFlags = m_TargetFlags;

        // Assumes caller is holding appropriate lock
        m_TargetFlags &= ~Flags;

        return oldFlags;
    }

    FORCEINLINE
    VOID
    SetRequestBaseFlags(
        __in UCHAR Flags
        )
    {
        // Assumes caller is holding appropriate lock
        m_RequestBaseFlags|= Flags;
    }

    SHORT
    GetVerifierFlagsLocked(
        VOID
        )
    {
        ASSERT(GetDriverGlobals()->FxVerifierOn);
        return m_VerifierFlags;
    }

    FORCEINLINE
    SHORT
    GetVerifierFlags(
        VOID
        )
    {
        SHORT flags;
        KIRQL irql;

        Lock(&irql);
        flags =  GetVerifierFlagsLocked();
        Unlock(irql);

        return flags;
    }

    FORCEINLINE
    VOID
    SetVerifierFlagsLocked(
        __in SHORT Flags
        )
    {
        m_VerifierFlags |= Flags;
    }

    FORCEINLINE
    VOID
    SetVerifierFlags(
        __in SHORT Flags
        )
    {
        KIRQL irql;

        ASSERT(GetDriverGlobals()->FxVerifierOn);

        Lock(&irql);
        SetVerifierFlagsLocked(Flags);
        Unlock(irql);
    }

    FORCEINLINE
    VOID
    ClearVerifierFlagsLocked(
        __in SHORT Flags
        )
    {
        m_VerifierFlags &= ~Flags;
    }

    FORCEINLINE
    VOID
    ClearVerifierFlags(
        __in SHORT Flags
        )
    {
        KIRQL irql;

        ASSERT(GetDriverGlobals()->FxVerifierOn);

        Lock(&irql);
        ClearVerifierFlagsLocked(Flags);
        Unlock(irql);
    }

    FORCEINLINE
    VOID
    VerifierSetFormatted(
        VOID
        )
    {
        if (GetDriverGlobals()->FxVerifierOn &&
            GetDriverGlobals()->FxVerifierIO) {
            SetVerifierFlags(FXREQUEST_FLAG_FORMATTED);
        }
    }

    FORCEINLINE
    VOID
    VerifierClearFormatted(
        VOID
        )
    {
        if (GetDriverGlobals()->FxVerifierOn &&
            GetDriverGlobals()->FxVerifierIO) {
            ClearVerifierFlags(FXREQUEST_FLAG_FORMATTED);
        }
    }

    FORCEINLINE
    BOOLEAN
    VerifierIsFormatted(
        VOID
        )
    {
        if (GetDriverGlobals()->FxVerifierOn &&
            GetDriverGlobals()->FxVerifierIO) {
            return (GetVerifierFlags() & FXREQUEST_FLAG_FORMATTED) ? TRUE : FALSE;
        }
        else {
            //
            // we are not tracking the state
            //
            return TRUE;
        }
    }

    FORCEINLINE
    BOOLEAN
    ShouldClearContext(
        VOID
        )
    {
        return (m_RequestBaseFlags & FxRequestBaseSyncCleanupContext) ? TRUE
                                                                      : FALSE;
    }

    _Must_inspect_result_
    NTSTATUS
    CreateTimer(
        VOID
        );

    VOID
    StartTimer(
        __in LONGLONG Timeout
        );

    _Must_inspect_result_
    BOOLEAN
    CancelTimer(
        VOID
        );

    BOOLEAN
    Cancel(
        VOID
        );

    BOOLEAN
    FORCEINLINE
    IsAllocatedFromIo(
        VOID
        )
    {
        return m_IrpAllocation == REQUEST_ALLOCATED_FROM_IO ? TRUE : FALSE;
    }

    BOOLEAN
    FORCEINLINE
    IsAllocatedDriver(
        VOID
        )
    {
        return m_IrpAllocation == REQUEST_ALLOCATED_DRIVER ? TRUE : FALSE;
    }

    BOOLEAN
    FORCEINLINE
    IsCanComplete(
        VOID
        )
    {
        return m_CanComplete;
    }

    FORCEINLINE
    VOID
    SetCompleted(
        __in BOOLEAN Value
        )
    {
        m_Completed = Value;
    }

    VOID
    FORCEINLINE
    SetPriorityBoost(
        CCHAR PriorityBoost
        )
    {
        m_PriorityBoost = PriorityBoost;
    }

    CCHAR
    FORCEINLINE
    GetPriorityBoost(
        VOID
        )
    {
        return m_PriorityBoost;
    }

    FORCEINLINE
    WDFREQUEST
    GetHandle(
        VOID
        )
    {
        return (WDFREQUEST) GetObjectHandle();
    }

    FORCEINLINE
    static
    FxRequestBase*
    _FromListEntry(
        __in PLIST_ENTRY Entry
        )
    {
        return CONTAINING_RECORD(Entry, FxRequestBase, m_ListEntry);
    }

    FORCEINLINE
    static
    FxRequestBase*
    _FromDrainEntry(
        __in PSINGLE_LIST_ENTRY Entry
        )
    {
        return CONTAINING_RECORD(Entry, FxRequestBase, m_DrainSingleEntry);
    }

    FORCEINLINE
    static
    FxRequestBase*
    _FromCsqContext(
        __in PMdIoCsqIrpContext Context
        )
    {
        return CONTAINING_RECORD(Context, FxRequestBase, m_CsqContext);
    }

    FORCEINLINE
    PVOID
    GetTraceObjectHandle(
        VOID
        )
    {
        PVOID handle;

        handle = GetObjectHandle();

        if (handle != NULL) {
            return handle;
        }
        else {
            return (PVOID) this;
        }
    }

    VOID
    FreeMdls(
        VOID
    );

    __declspec(noreturn)
    VOID
    FatalError(
        __in NTSTATUS Status
        );

    VOID
    ClearFieldsForReuse(
        VOID
        );

protected:
    FxRequestBase(
        __in PFX_DRIVER_GLOBALS FxDriverGlobals,
        __in USHORT ObjectSize,
        __in_opt MdIrp Irp,
        __in FxRequestIrpOwnership Ownership,
        __in FxRequestConstructorCaller Caller,
        __in FxObjectType ObjectType = FxObjectTypeExternal
        );

    virtual
    ~FxRequestBase(
        VOID
        );

    // Do not specify argument names
    FX_DECLARE_VF_FUNCTION(
    VOID,
    VerifyDispose
        );

    // FxObject overrides
    virtual
    BOOLEAN
    Dispose(
        VOID
        );

    static
    MdDeferredRoutineType _TimerDPC;

    VOID
    CompleteSubmittedNoContext(
        VOID
        );

    VOID
    ZeroOutDriverContext(
        VOID
        )
    {
#if (FX_CORE_MODE == FX_CORE_KERNEL_MODE)
    RtlZeroMemory(GetSubmitFxIrp()->GetDriverContext(),
                  GetSubmitFxIrp()->GetDriverContextSize());
#else
    //
    // UMDF host doesn't expose any easier way to zero out the contexts so
    // set context to NULL one by one.
    //
    GetSubmitFxIrp()->SetContext(0, NULL);
    GetSubmitFxIrp()->SetContext(1, NULL);
    GetSubmitFxIrp()->SetContext(2, NULL);
    GetSubmitFxIrp()->SetContext(3, NULL);
#endif
    }

public:

    union {
        //
        // The cancel safe queues use this context to identify
        // the request in a race free manner.
        //
        MdIoCsqIrpContext m_CsqContext;

        //
        // IoTargets uses this to track the request when it is sent to the target.
        // Since the request cannot be on an CSQ and sent to a target at the
        // same time, we can unionize this with the CSQ context.
        //
        LIST_ENTRY   m_ListEntry;
    };

    union {
        //
        // IoTargest uses this when it needs to create a list of requests to cancel
        // when making a state transition
        //
        SINGLE_LIST_ENTRY m_DrainSingleEntry;

        //
        // If TRUE, the driver formatted the request by copying the current stack
        // location to next or by manually passing in an IO_STACK_LOCATION.  This
        // is union'ed with m_DrainSingleEntry b/c it is only relevant during
        // send and forget and the request is never enqueued on the target in
        // this case and m_DrainSingleEntry is used when tracking requests sent
        // on a target for cancelation due to a target state change.
        //
        BOOLEAN m_NextStackLocationFormatted;
    };

protected:
    //
    // The NT IRP is wrapped by a frameworks FxIrp
    //
    // Note: If m_Irp is NULL after initialization, this means
    //       the IRP was cancelled by a FxIrpQueue cancellation
    //       callback, or completed.
    //
    FxIrp              m_Irp;

    //
    // Target of the request.  Access to this field is unguarded.  The following
    // have access to this field
    // o The owning target itself
    // o _TimerDPC()
    // o Cancel() IFF it has successfully incremented the irp completion ref count
    //
    FxIoTarget* m_Target;

    FxRequestContext* m_RequestContext;

    FxRequestTimer* m_Timer;

    //
    // Client driver completion routine to call when the request has come back
    // from the target device.
    //
    FxRequestCancelCallback m_CancelRoutine;

    FxRequestCompletionCallback m_CompletionRoutine;

    //
    // Context to pass to CompletionRoutine when called
    //
    WDFCONTEXT m_TargetCompletionContext;

    //
    // Synchronization for this field is through Interlocked operations
    //
    LONG m_IrpCompletionReferenceCount;

    //
    // Access to flags guarded by FxIoTarget::Lock
    //
    // Values defined in the enum FxRequestTargetFlags
    //
    union {
        UCHAR m_TargetFlags;

        //
        // These are used purely for debugging, not in live code anywhere!
        // NOTE:  if FxRequestTargetFlagschanges, so this this union
        //
        struct {
            UCHAR Completed : 1;
            UCHAR FlagsPended : 1;
            UCHAR TimerSet : 1;
            UCHAR CancelledFromTimer : 1;
            UCHAR IgnoreState : 1;
        } m_TargetFlagsByName;
    };

    //
    // Contains a value from the enum type FxRequestAllocationSource describing
    // how the irp was allocated
    //
    UCHAR m_IrpAllocation;

    BOOLEAN m_Completed;

    BOOLEAN m_Canceled;

    WDFOBJECT_OFFSET_ALIGNED m_SystemBufferOffset;

    union {
        //
        // These are flags used by verifier.  Set with values from the enum
        // FxRequestVerifierFlags
        //
        SHORT m_VerifierFlags;

        struct {
            SHORT DriverOwned : 1;
            SHORT TagRequest : 1;
            SHORT Forwarded : 1;
            SHORT DriverDispatch : 1;
            SHORT DriverCancelable : 1;
            SHORT DriverInprocessContext : 1;
            SHORT Cancelled : 1;
            SHORT Formatted : 1;
            SHORT SentToTarget : 1;
            SHORT DriverInEvtIoStopContext : 1;
        } m_VeriferFlagsByName;
    };

    //
    // If this is !=0, its an indication of outstanding references
    // on WDM IRP fields such as any system buffers.
    //
    LONG m_IrpReferenceCount;

    // This field !=NULL if the request is on an IrpQueue.
    FxIrpQueue*        m_IrpQueue;

    WDFOBJECT_OFFSET_ALIGNED m_OutputBufferOffset;

    union {
        //
        // Bit field.  Set with values from the enum FxRequestBaseFlags
        //
        UCHAR m_RequestBaseFlags;

        struct {
            UCHAR SystemMdlMapped : 1;
            UCHAR OutputMdlMapped : 1;
            UCHAR SyncCleanupContext : 1;
        } m_RequestBaseFlagsByName;
    };

    union {
        //
        // Bit field.  Set with values from the enum FxRequestBaseStaticFlags
        //

        //
        UCHAR m_RequestBaseStaticFlags;

        struct {
            UCHAR SystemBufferValid  : 1;
            UCHAR OutputBufferValid  : 1;
        } m_RequestBaseStaticFlagsByName;
    };

    //
    // Priority boost.
    //
    CCHAR m_PriorityBoost;

    //
    // Contains values from FxRequestCompletionState
    //
    BYTE m_CompletionState;

    //
    // TRUE, request can be completed by the driver.
    //
    BOOLEAN m_CanComplete;

    //
    // If !=NULL, MDL allocated and assocated with the request
    //
    PMDL m_AllocatedMdl;
};

#if ((FX_CORE_MODE)==(FX_CORE_KERNEL_MODE))
#include "FxRequestBaseKm.hpp"
#else if ((FX_CORE_MODE)==(FX_CORE_USER_MODE))
#include "FxRequestBaseUm.hpp"
#endif

#endif // _FXREQUESTBASE_H_

redpajama_set_name: RedPajamaGithub


text:
Hurricane Michael: Life at the end of the road on Alligator Point
People walk around the destroyed portion of Alligator Drive in Alligator Point on Friday. Alligator Drive, along with several structures were destroyed in when Hurricane Michael hit the area. (TAILYR IRVINE | Times)
Corinna McEwen, 50, and Jack Tully, 43, pose for a portrait near the destroyed portion of Alligator Drive in Alligator Point on Friday. Hurricane Michael also destroyed McEwen's business the Tiki Hut. (TAILYR IRVINE | Times)
Power lines lean against the trees on Alligator Drive in Alligator Point on Friday. (TAILYR IRVINE | Times)
Residents assess the damage to their home after Hurricane Michael hit Alligator Drive in Alligator Point on Friday. (TAILYR IRVINE | Times)
Rob and Connie Clark, walk their bikes around the destroyed portion of Alligator Drive in Alligator Point on Friday. With part of Alligator Drive undrivable, residents have to find alternative ways to get to their homes. (TAILYR IRVINE | Times)
Powerlines lean into homes on Alligator Drive in Alligator Point on Friday. (TAILYR IRVINE | Times)
A Coast Guard helicopter flies over Alligator Drive in Alligator Point on October 12, 2018. A large portion of Alligator Drive was destroyed by Hurricane Michael leaving residents unable to drive to their homes. (TAILYR IRVINE | Times)
By Howard Altman
Published October 12 2018
Updated October 12 2018
ALLIGATOR POINT — Wearing a bright yellow volunteer firefighter T-shirt and a weary smile, Corinna McEwen trudged past a group of Florida National Guard soldiers.
They were sent Friday to help clear Alligator Drive, the road leading to her beachfront bar, the Alligator Point Tiki Hut. It's a popular hangout for longtime residents and vacationing homeowners.
Or it was until Hurricane Michael devastated much of the Panhandle this week.
The storm washed away a 2-mile stretch of Alligator Drive, leaving behind just a few sections of buckled asphalt and concrete. The Tiki Hut is gone, too.
TAMPA BAY TIMES COVERAGE: HURRICANE MICHAEL
DAY THREE: Thousands of people reported missing after Hurricane Michael
GROUND ZERO: 'We're broken here': Mexico Beach reels in the aftermath of Hurricane Michael
FOUR REASONS: Learn why Hurricane Michael was so devastating
30 IMAGES: The Times eyewitness account to damage inflicted by Hurricane Michael after landfall
INTERACTIVE: Track Hurricane Michael flooding in real time
McEwen and her Alligator Point stalwarts gained a bit of notoriety as Michael swirled ominously toward them. Franklin County Sheriff A. J. Smith called out residents who refused to leave.
"He called us the hard-heads," McEwen said, with a sly, prideful smile. She showed off a photo of her standing in front of the roaring surf, arms spread wide, defying the coming storm.
She stayed all right. But everything she built is gone.
"Back in February, I left a 25-year career as a dental hygienist to become a bar owner," McEwen said. "I must have been insane. I just turned 50 and was going through a mid-life crisis. Now I have no bar and no job."
McEwen walked past a dozen tan and green National Guard vehicles, most capable of traversing deep water, parked on the side of what was left of Alligator Drive, the only road in and out of Alligator Point.
The troops arrived shortly after 4 p.m. Thursday to clear roads and provide security.
Like much of the Panhandle, the area is without power, though residents did have running water.
Soldiers spent hours working with Air National Guard engineers in front-end loaders, clearing mounds of sand, downed trees and building debris. As the last flashes of pink sky faded to black, they patrolled what used to be the roadway.
"We want people to know we are out here," said Lt. Tom Wagner. "When people know we are out there, it keeps the looters away."
After the sun peaked Friday morning, the troops geared up for the day and awaited orders. Leaning against a tan Humvee, Capt. Erich McCartney talked to headquarters about his plans.
"We are going to try and push out to the point," said McCartney, 37, as the Air National Guard showed up with heavier equipment than the front-end loaders they were using the night before.
In the military, McCartney leads an artillery unit. But it was his civilian calling is what prepared him for this mission.
The Tampa resident is a civil engineer who owns Greyfox Construction.
"We do a lot of work with the Department of Transportation," he said.
Further on down Alligator Drive, Kevin Perez joined those who will spend the next days cleaning up after the storm.
"Other than smelling like fish, our house is in pretty good shape," he said. "Everybody lost the ground floor stuff though."
He and his wife Carmen originally planned on riding out Michael. But by 4 a.m. Wednesday, they changed plans.
"It was getting really scary, really rough," he said. "So we left."
By the time he came back, his road was gone several hundred yards from his house.
"It happens every time we have a hurricane," he said. "The road goes away."
Despite being reinforced by two big front-end loaders and a dump truck, Capt. McCartney said the decision was made to pull the plug on trying to push out and repair Alligator Drive.
The damage was too heavy, he said.
"We did what we came to do and cleared out what we could," he said. "There are other areas that need to be cleared now."
Residents living on Alligator Point beyond where the road washed out are relying on four-wheelers or foot to get back and forth.
The lack of road didn't stop Rob and Connie Clarke from making their way via bicycle to what used to be the Tiki Hut and neighboring marina, which also suffered heavy damage.
"We have a house out there, so we figured the road might be damaged," said Rob Clarke, 61, a lawyer in Tallahassee. "That's why we brought our bikes."
The Tiki Hut was one of the couple's favorite places to visit.
"We really enjoy the camaraderie with the locals and tourists," said Rob Clarke. "This was a great gathering place. It is sad to hear that it was destroyed."
His favorite food?
"The grouper sandwich," he said.
A man who said he was the owner of the Alligator Point Marina was in no mood to talk to reporters and ordered them off the property.
A short while later, McEwen and her boyfriend, Jack Tully, 43, pulled up a side road that used to end at Alligator Drive, back before it was washed away.
"I'm going to miss that, too," said Tully when told about the man gushing about the grouper sandwich. "I am going to miss it all."
McEwen, who rents the property from the marina, said she will try to rebuild, but that nothing is guaranteed.
On her way up Alligator Drive, she waxed philosophic.
"If it doesn't work out, I can always go back to cleaning teeth," she said.
Contact Howard Altman at haltman@tampabay.com. Follow @haltman.
Howard Altman
Military Affairs and General Assignment Reporter
Tropical Storm Barry has arrived, expected to become a hurricane by Friday
The storm is heading to the other side of the Gulf of Mexico, but will send threatening conditions to the Florida coast.
Georgia low pressure could become tropical depression today, then season's first hurricane
The system, which started as weak low pressure over Georgia, now has a 100 percent chance of forming into a tropical depression within two days, forecasters say.
Latest storm forecast holds steady: six hurricanes, two big ones.
Colorado State University's latest hurricane forecast doesn't deviate from its earlier predictions. Scientists still foresee an average storm season.
Thanks a lot, Georgia: Tropical depression likely to develop in Gulf of Mexico.
An area of low pressure over central Georgia is heading to the warm Gulf waters. Tampa Bay could see a lot of rain this week.
Hurricanes, home insurance and how to make sure you're prepared
The process of filing a disaster claim can be stressful. Here are some tips for how to get ready.
Hurricane Michael destroyed their homes. Then the insurance heartache began.
Nine months after the storm, more than 20,000 property claims remain outstanding in Florida.

redpajama_set_name: RedPajamaCommonCrawl


Critically acclaimed novelist Eliot Pattison already had a successful career as an international attorney when he began writing fiction, inspired by his many visits to China and Tibet. His first novel, The Skull Mantra (St. Martin's Minotaur), won the Edgar Award for Best First Novel, received rave reviews from critics and launched a new series. Set in China and Tibet, the series features former Beijing inspector Shan Tao Yun, who has been sentenced to a hard labor camp in Tibet for offending a communist party official. Shan solves a crime and starts a new life in Tibet. Eliot spoke to us about the latest book in this entertaining and thought-provoking series, Bone Mountain (St. Martin's Minotaur), and how his travels to Chinese-occupied Tibet have changed his life.
An information developer for IBM for nineteen years, Steve Hamilton always had a secret longing to write fiction. His first book, A Cold Day in Paradise won the PWA/St. Martin's Press Best First Private Eye Novel Contest, and went on to win both the Edgar and the Shamus awards, as well. Now he juggles two careers, while writing his bestselling series about an ex-cop, Alex McKnight, who lives in Michigan's Upper Peninsula. His latest book is Blood is the Sky (St. Martin's Minotaur), a gripping tale of friendship and revenge. Steve spoke to us about his latest novel and how he manages to keep two successful careers going at the same time.
Visit our Book Review section to see what our reviewers have to say about the latest books. See our new reviews this month in these genres: children's, mystery/thriller, romance, fantasy/SF and nonfiction.
British novelist Alex Keegan once took a screenwriting class which quickly degenerated into the class yelling out every cliché they could think of. So, how does a writer learn to write really original literary fiction? In this fascinating article, Alex Keegan takes you on a guided tour inside the mind of a novelist as his style evolves over the years.
Australian children's author Hazel Edwards gives readers a behind the scenes tour of how she created her upcoming new young adult eco-thriller, Frozen Chosen (Lothian, 2004). From plotting to character creation, Hazel tells all about her exciting new project.
How do savvy songwriters know instinctively how to use both melodic and lyrical repetition effectively? This month nationally syndicated radio talk show host, songwriter and CEO of CQK Music & Records Mary Dawson tells you how in her new article, "The Power of Repetition."
Freelancing is not an easy way to make a living. But there are some things that can help you get the editor's attention and get that assignment. Gary Bell explains in his article, "Eight Tips For Getting Published in Magazines."


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October 9, 2019 By Saloni PC Games
The not-so-humble PC is the biggest gaming platform on the planet, and will likely remain so as long as we have electricity and an Internet connection (in that order). Amid the sheer quantity of games released – thousands every year when you take the bright indie space into account – there's a growing list of quality titles. The list below is all killer, no filler, and hopefully has something for everybody.
Come on, now. You didn't think you could get through a best of list without seeing this did you? Though Fortnite has its detractors in the PC gaming community (think: that weird hatred that comes from being "too popular") I have to give it its dues here today.
Basically, any game that is big enough to award a $3 million esports prize gets to be on this list by default.
"What's a Fortnite?" you might be asking yourself, as you sit on Mars in your cave, with two fingers in your ears. It's a third-person shooter battle royale that's equal parts gunplay and building cubby houses.
Essentially, 100 players are air dropped onto an island and are asked to go the tonk until only one of them remains. Success revolves around tactically using your terrain (or just building your own to get that Obi wan "higher ground advantage").
Scavenging the world for better randomised guns is also a must, as is getting out of Dodge when the playable area shrinks (out of bounds is cancer). Those are the basics of what can become an incredibly complex and intense online experience.
Go in forewarned, though: competition is fierce and the dance-based taunts from nine year olds, merciless.
I find it very unlikely that you haven't already heard the legends of this. The legends of the ridiculously large league of players who play…er, well, League of Legends. Once played by roughly 100 million players globally, this multiplayer online battle arena (or MOBA) has become an esport on its own level.
New champions are crowned constantly, too, as the tactics are ever-changing in this rapid-fire video game where actions and defeats are measured in milliseconds and there's a playstyle for every taste.
You can doggedly hold choke points as a Leonidas-level tank, turn the fortunes of your team with a support class, or shred lifebars with the showiest crit hits this side of an anime.
That being said, a lot of hard work and preternatural hand-eye coordination stands between you and the big leagues. Effective time management of your forces and having good communication with players willing to dovetail into one cohesive strategy are a must.
Even better, a constantly expanding roster of champions means this hyper-competitive battlefield never has a chance to go stagnant. Consider yourself warned: the large-scale conflicts of League of Legends become sheer addiction in no time flat.
The Joker arrives in Mortal Kombat 11 next month – and crossplay multiplayer is coming too


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Filip Raičević (, ; born 2 July 1993) is a Montenegrin footballer who plays for Italian  club Taranto.

Raičević also holds Belgian passport.

Club career
Born in Podgorica, the capital of Montenegro, Raičević started his career at Serbian club FK Partizan.

Lucchese
Raičević was signed by Italian Serie D club Lucchese in February 2014. He followed the club promoted to 2014–15 Lega Pro.

Vicenza
Raičević was signed by Italian Serie B club Vicenza on 22 July 2015 for €50,000 transfer fee, in a 3-year contract, with Niko Bianconi moved to Lucchese in a temporary deal.

On 31 January 2017 Raičević and Cristian Galano were left for Bari in temporary deals from Vicenza, with an obligation to sign them outright. On the same day Giuseppe De Luca and Souleyman Doumbia moved to the Veneto-based club from Bari in temporary basis.

Livorno

Loan to Śląsk Wrocław
On 27 January 2020 he joined Polish club Śląsk Wrocław on loan until the end of the 2019–20 season.

Loan to Ternana
On 3 October 2020 he joined Ternana on loan with an option to buy.

Piacenza
On 4 November 2021, he signed a one-season deal with Piacenza.

International career
Raičević was a player of Montenegro U17 in 2009–10 season. He scored once in 2010 UEFA European Under-17 Championship qualifying round, out of possible 3 matches. He received a call-up from Montenegro under-18 team in 2010–11 season.

He made his senior debut for Montenegro in a March 2016 friendly match against Greece and has, as of October 2020, earned a total of 3 caps, scoring no goals.

References

External links

1993 births
Living people
Footballers from Podgorica
Belgian people of Montenegrin descent
Association football forwards
Montenegrin footballers
Montenegro youth international footballers
Montenegro international footballers
S.S.D. Lucchese 1905 players
L.R. Vicenza players
S.S.C. Bari players
F.C. Pro Vercelli 1892 players
U.S. Livorno 1915 players
Śląsk Wrocław players
Ternana Calcio players
Piacenza Calcio 1919 players
Taranto F.C. 1927 players
Serie D players
Serie B players
Serie C players
Ekstraklasa players
Montenegrin expatriate footballers
Expatriate footballers in Italy
Montenegrin expatriate sportspeople in Italy
Expatriate footballers in Poland
Montenegrin expatriate sportspeople in Poland

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How do I transform an interested prospect into a committed, paying client – without feeling like a pushy salesman?
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Where am I going to find people who want to pay me for what I do?
Where do I start with online marketing?
How do I structure my business to make more money in less time?
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The 10 Things You Must Do When Shooting a Movie at 18,000 Feet
Jon Fitzgerald
"The Highest Pass" started at sea level — less than a mile, in fact, from the ocean in Marina del Rey. I had just finished a documentary called "The Back Nine" and was ready for another adventure.
The most danger I faced on my last project was going down a steep hill in a golf cart going less than 20 mph. "The Highest Pass" was quite the opposite — this project would take me to the other side of the world, following seven motorcycle riders on the most dangerous roads on the planet, climbing to over 18,000 feet.
Adam Schomer came to me with a pretty straightforward pitch – A modern Indian yogi leading a group through the Himalayas, to the highest motorable road in the world, on motorcycles. But here's the hook: The yogi was carrying a prophecy given to him at birth — that he would die in an accident, at the age of 27. And yes, he was 27.
That's all I needed. I was in.
Having practiced meditation on and off for years, I was intrigued by the idea of going to India to make a film. Our company tagline is to "enlighten through entertainment" and this project certainly fit that philosophy; also, the self-help/spiritual arena is the fastest-growing market sector. If we could shoot this on a tight budget, I felt like we had a good chance to make our money back. Selfishly, I also knew the journey had the potential to be a transformational experience.
Here are 10 key lessons I learned along the way:
1. Have a good reason for making the film.
I wanted to make engaging films with some social relevancy and audience impact. After talking through a rough story structure, I knew this project would incorporate powerful themes and hoped the project would prove inspirational. A spiritual adventure, done well, would attract a variety of demographics. Adam knew he wanted to explore the idea of fear and there would be plenty of it. Of course, riding motorcycles on dangerous roads would fit the obvious definition, but the word would take on new meaning for everyone involved. The riders brought their own personalities (and their own issues) to the party.
2. Be prepared for the elements.
When you know that it's going to be 80 degrees at the start of the journey, but that you will end up in the snow toward the end, you have to cover your bases. Shorts and T-shirts for day one. Jeans and a sweatshirt for day two and the layers pile on from there. Eventually, you will be in freezing temperatures and will need a good sleeping bag, warm gloves and hiking boots. Pack light, but with enough to not have to do laundry. And, of course, with escalating altitudes, have plenty of herbs and cases of water. Four big bottles per day, per person, was the average. We even packed oxygen.
3. Lower your standards.
Most of us are fortunate enough to have access to clean bathrooms, daily showers and reasonable dietary choices. In India, not all accommodations had showers. Toilets were often scarce and you never knew what food would be available. Yes, you have the pleasure of sampling some amazing home-cooked meals by the locals in the middle of nowhere, but plenty of power bars and trail mix came in handy. And don't count on heaters in tents and remote accommodations. Heat packs in the sleeping bag did the trick.
4. Expect the unexpected.
This is a great example where Murphy's Law meets Serendipity. When you're in a foreign country and packing thousands of dollars of camera gear with $10,000 cash in your pocket, expect to get stopped at customs. Guards questioned me, but I stressed my "interest in photography…I was going to be in such a beautiful region." Eventually, they let me through. But then my driver, who picked me up at 4am, had a car without a trunk, didn't know where he was going and nearly crashed at least a dozen times. Talk about fear right out of the gate.
On the other side of the coin, we had the pleasure of kicking off production in Rishikesh, the birthplace of yoga. And just a few days later, wild horses greeted us at 15,000 feet. We met a distinguished oracle, witnessed spectacular cultural rituals in Ladakh and were treated to stunning geography for days on end.
5. Choose your team carefully.
In many films, you hire the actor who will help with distribution, regardless of their personality. Then you hire craftspeople with the best resume who you learn to tolerate for production days. But when you are in distant locations, spending countless hours on the road and sleeping in tight quarters, it's even more important to have a strong connection with your principal team. I was fortunate that I really enjoyed the cast (the riders) and crew and most important, our DP Dean Mitchell. We were side-by-side in the production van for hours at a time, downloading footage into the wee hours of the night and planning the next day's shoot.
6. Learn to embrace fear.
I knew going in that we would be on some dangerous roads, in difficult filming conditions, but I was not prepared for many of the other risks. One of the realities of the passes of India is the constant flow of huge trucks. These monsters come screaming around corners on one-lane roads. Our driver was honking every other minute, and I was peeking out of the corner of my eye as we missed that truck by a matter of inches, all day long. You see the rusted metal of cars on the bottom of cliffs below and there are no rails. At some point, a few days into the madness, I had no choice but to relinquish the fear. If it was my time to go, there wasn't anything I could do about it. On the first day of the journey, one of the riders was clipped by a truck and we were in the ER. Fortunately, no broken bones. Same thing on day two. The riders had to learn to ride on these roads and in the rain, through streams and over ice. So they had their own fears to conquer, but the crew was stuck in the iron cage and we had to learn to embrace it.
Note: A few months after production, one of our drivers was killed in a car accident.
7. Be a diplomat.
When you are filming riders focused on their survival and on their own personal journeys, it's hard to ask them to stop and "do it again." But this was a shoot without a scout and the production vans could not always keep up. We would pull around a corner and see the perfect shot, but the riders would be miles ahead by then. You have to be selective about your shots and know you only have so many chips to play. And most film crews are familiar with standard meal breaks and overnight turnaround time. This wasn't happening on "The Highest Pass." We were chasing the light or trying to get to a destination before fatigue became dangerous for the riders. As the director, you are in the middle and have to understand the art of the give and take. You need the subjects to respect you, but don't want the crew bitterly going through the motions because they are feeling resentful.
Show your appreciation. Find the compromises for both sides. And then you have the locals. They don't care if you're making a movie, unless George Clooney is one of the riders. You are the outsider and have to play by their rules. From accommodations to local police, diplomacy really helps the cause.
8. Back up the footage.
Regardless of how tired you are after your 15-hour day, you have to download all the cards (movie files) onto G-Raids and LaCie drives. This can take a few hours and you typically want more than one copy whenever possible. In our case, we had three cameras filming all day long so there was a lot of footage to download. It's important to force yourself to make this happen. Even if you are operating on 4-5 hours sleep a night, at least your cameras can start fresh the next day and you have the insurance of footage back-up. In most cases, there are no reshoots on this type of project.
9. Have an open mind.
If you are shooting a narrative feature, you have the luxury of a script. If you are shooting a documentary, chances are, you just have a treatment, outline or general structure in mind before you roll cameras. In our case, we started with our riders, a goal of reaching the highest pass and Joseph Campbell's "Hero's Journey" as a road map. As the adventure unfolded, Adam and I shifted gears. We singled out Adam as a rider (who had just learned how to ride a motorcycle a few weeks before the trip) and made him the hero, with Anand as his mentor. It may seem obvious, but it's often difficult for directors to be open to modifying a pre-existing structure. Many of the best documentaries ever made changed plans during shooting. Hoop Dreams, for example, was initially going to be a 30-minute documentary for PBS. They realized they were onto something special and tracked the players much longer than anticipated and ended up with what Roger Ebert called "the best film of the decade."
10. Enjoy the ride!
It may seem clichéd, but filmmaking is an amazing opportunity, an incredible journey. How blessed we are to share stories for a living — from the inception of the idea, through reaching your audience, to the feedback and the effects. Each stage has its peaks and valleys. When we agreed to make "The Highest Pass," we were not sure what the movie would be, but we had high hopes for an engaging project. With some festival experience, I had a good feeling this film would work on that circuit, but we didn't expect a theatrical release.
We bucked tradition and had our world premiere at a smaller event, the Topanga Film Festival. What an amazing experience, to see it on the screen with the right audience, overflowing in the aisles. Then it won a top prize, won a few more awards on the circuit and is being theatrically released by Cinema Libre Studio on April 27. Everyone at the studio truly supports socially relevant films and they are working hard to give the film a fair shot. Our team has had a remarkable experience and look forward to bringing the movie to audiences in a variety of platforms.
Our initial goal stands. We hope people are engaged and inspired to look deeper into themselves and the world around them.
"The Highest Pass" opens today in Los Angeles. In the fall of 2011, Fitzgerald launched CineCause, a company that connects socially relevant films, celebrities and news to related causes. Prior to that, he directed three feature documentaries: "The Back Nine," "The Highest Pass" and "Dance of Liberation." From 2003-2007, Fitzgerald provided consulting services to many film festivals and indie filmmakers, via Right Angle Studios. He was a co-founder of the Slamdance Film Festival in 1995 and was the festival director at the American Film Institute and the Santa Barbara and Abu Dhabi International Film Festivals.
This Article is related to: Toolkit and tagged


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Q: Problems with IMetaDataImport::ResolveTypeRef Method I have my own debugger for .NET apps that uses IMetaDataImport interface
When I call ResolveTypeRef method, I always get NotImplementedException.
The definition of ResolveTypeRef is like this:
[ComImport]
[Guid("....")] //a valid GUID
[InterfaceType(ComInterfaceType.InterfaceIsIUnknown)]
[CLSCompliant(false)]
public interface IMetaDataImport {
  void ResolveTypeRef(
    [ComAliasName("mdTypeRef")] mdToken tr,
    [ComAliasName("REFIID")] ref Guid riid,
    [ComAliasName("IUnknown**"), Out, MarshalAs(UnmanagedType.IUnknown)] out object ppIScope,
    [ComAliasName("mdTypeDef*"), Out] out mdToken ptd
  );
  // ... other methods from IMetaDataImport
}

The method calling:
metadataImport.ResolveTypeRef(typeRefToken, ref metadataImportGuid, out metadataObject, out typeDefToken)

Typically, the method should resolve type System.Exception or System.SystemException.
The problem occured when I moved app from .NET 3.5 to .NET 4.
Thanks for the answers!

A: Uff, I finally get rid of this ... The solution is not call ResolveTypeRef, but create your own method to resolve type:
  mdToken ptkResScope;
  uint len;
  metadataImport.GetTypeRefProps(typeRef, out ptkResScope, null, 0, out len);
  StringBuilder sb = new StringBuilder((int)len);
  metadataImport.GetTypeRefProps(typeRef, out ptkResScope, sb, len, out len);
  string className = sb.ToString();
  foreach (loadedModule ) {   // this is quite tricky part ...
    metadataImportForLoadedModule = GetMetaDataImportForModule(loadedModule);
    metadataImportForLoadedModule.FindTypeDefByName(className, mdToken.Nil, out typeDef);
    if ( typeDef.IsNonNil(CorTokenType.mdtTypeDef) ) {
      return typeDef;
      }
    }

The idea comes from David Broman's CLR Profiling API Blog: Metadata Tokens, Run-Time IDs, and Type Loading (really good reading if you are interested in MetaDataImport).

A: If you actually try and step into the method ResolveTypeRef, it seems you actually end up at SymMethod::GetSourceStartEnd which is what is returning E_NOTIMPL. Furthermore, if you have a look at the vtable in IDA, as far as I can see the method ResolveTypeRef doesn't even exist on IMetaDataImport/2's vtable; rather, it is a method on CordbModule, however evidently isn't actually exposed in the ICorDebugModule interface.
In any case, the conclusion here appears to be that Microsoft's documentation/header files are out of date with the actual implementation

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I might be able to help - direct or indirect-when I sent a bundle of problems to the forum builders.
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Root rockers Heavy Feather are finally back with their new single "Mountain of Sugar", out everywhere on Friday, November 27, 2020. The single is the title track and second taste of their upcoming sophomore album 'Mountain of Sugar', to be released by The Sign Records in spring 2021. 60's and 70's rock influences and strong, raw vocals from blues singer Lisa Lystam are at the core of the new release.
"Mountain of Sugar" is an upbeat roots rock track; oozing with a 70's sound and feel, filled with attitude and raw vocals from blues singer Lisa Lystam. Catchy hooks and roaring guitar riffs based on influences from the greats of the 60s and 70s gives the listener a taste of the upcoming record. Hints of everything from psychedelic and classic rock influences are combined with the band's unique take on roots- and blues rock, creating a solid track impossible to ignore.
Listen to "Mountain Of Sugar" HERE: https://orcd.co/heavysugar
When Heavy Feather's first album "Débris & Rubble" (2019) was released it became praised by both press and audience; taking the band out to tour Europe. Now it´s time for their second album: Mountain of sugar – an even rawer, heavier and harder release than the previous one, still with the root rock and psychedelic touch at the very core.
2020 started off with the band going into the No Regrets Fonogram Studio in Stockholm to record an album filled with soul and creativity. Still with musical roots in the 60's, the result was a rock album with a modern twist that undoubtedly fills a void on the rock scene today. Just like their first album, this one was also recorded together with the producer Erik "Errka" Petersson. With some help from Pink Floyd's former mixer table, he gave the songs completely new dimensions. In addition, the band had the honor to work with Magnus Lindberg, who has previously mastered bands such as Lucifer and Imperial State Electric.
The new single "Mountain of Sugar" will be released on Friday, November 27, 2020.
Heavy Feather's upcoming sophomore album 'Mountain of Sugar' is to be released April 9, 2021, on vinyl and digital formats via The Sign Records.
Watch the video for "Bright In My Mind" HERE:
The new single "Bright in My Mind" will be released on Friday, October 23. Heavy Feather's upcoming sophomore album "Mountain of Sugar" is to be released April 9, 2021, on vinyl and digital formats via The Sign Records.
by: staff November 27, 2020
2021bluesclassic rockHeavy FeatherLisa Lystammountain of sugarnew albumpsychedelicrockthe sign records
ELEINE – new album, 'Dancing in Hell', out now
PERCHTA – An Interview with the Artist


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Omicron may infect half of Europeans within weeks, WHO says
Spanish government's request to consider Covid-19 as being in 'endemic' phase dismissed as premature by officials
Hans Kluge described the Omicron variant as a "tidal wave sweeping across the region"
Photo credit: Foto: AFP
More than half of Europe's population may be infected with Omicron within weeks at current transmission rates, a World Health Organization official has said.
The fast-spreading variant represents a "west-to-east tidal wave sweeping across the region," said Hans Kluge, the regional director of the WHO for Europe at a briefing on Tuesday. He cited forecasts by the Institute for Health Metrics and Evaluation that the majority of Europeans could catch it in the next six to eight weeks.
The latest Covid surge has so far resulted in fewer symptomatic cases and lower death rates than in previous waves, fuelling optimism the pandemic may be easing. However, the WHO has repeatedly warned against underestimating the Omicron strain as mild. Kluge said hospitalisation rates are increasing in Europe, which is putting pressure on health systems.
Separately, another WHO official said it's too early to consider that Covid-19 is moving into an endemic phase, a question that the Spanish government has suggested it's time to debate.
An endemic phase would see "stable circulation of the virus at predictable levels, but what we're seeing at the moment coming into 2022 is nowhere near that," said Catherine Smallwood, senior emergency officer at WHO Europe.
"We still have a huge amount of uncertainty, we still have a virus that's evolving quite quickly and posing new challenges," she said. "We're certainly not at the point of being able to call it endemic."


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Writer Kevin Holohan reflects on "the passing of one of the most imaginative writers I have ever read" in this obituary from January 2012.
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If your opponent is Alain Delon, you have no chance. Even if you're Mick Jagger.
Salvador Dalí walking her anteater, 1969.
Osama bin Laden on holiday with his family, Sweden, 1970.
Fashion hats, New York, 1939.
Alfred Hitchcock playing with grandchildren, 1960.
Students at Princeton University after playing with snowballs, 1893.
George Lucas and Steven Spielberg playing with water guns, Sri Lanka, 1983.
Woman 106 years Armenia defends his house, 1990.
Loading a 5MB hard drive of IBM, 1956.
Floods in Paris in 1924.
Ernest Hemingway and the consequences of the party.
Women protesting against the forced use of hijab in Iran a day after the Islamic revolution in 1979.
The last photo of the Titanic sailing on the water, 1912.
Audrey Hepburn shopping with her fawn, Beverly Hills, 1958.
Dior models walk the streets of Moscow in Soviet, 1956 period.
French man lights his cigar from Winston Churchill, 1944.
Pause smoking in building RCA Building, 1932.
The seal on the tomb of Tutankhamun, 1922. He remained intact for 3245 years.


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Happy Tuesday and hello from Boston! We are having the BEST time exploring this gorgeous city and surrounding states! We have been constantly on the move exploring and absorbing ALL of the Fall goodness!
Today I am sharing a gorgeous mommy and me look for fall. I am IN LOVE with both of our outfits. I had Olivia's outfits picked out for this trip for about a month. I usually get her's covered first and then start looking for mine. I came across this gorgeous Chelsea + Violet skirt while shopping at my local Dillards and knew it had to come with me to Boston. The texture and of course color had me at hello and I knew immediately I wanted to do a monochrome look. I paired it with a ruffle sweater and my favorite otk boots. I also picked up this beret last month and have been dying to wear it. These were shot in New Hampshire and I WISH I would have gotten some shots of the mountains. It was breathtaking! Fall Foliage as far as the eye could see.
Beautiful photos and outfits! Those colors are amazing, and your outfits are too cute!
I love, love, love this. Olivia is so adorable. Boston is our favorite place. We went there couple years ago but in the Summer. Your pictures make me want re visit in the Fall.


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Investigational New Drugs
August 2019 , Volume 37, Issue 4, pp 693–701 | Cite as
Phase I dose-escalation study of F14512, a polyamine-vectorized topoisomerase II inhibitor, in patients with platinum-refractory or resistant ovarian cancer
Alexandra Leary
Christophe Le Tourneau
Andrea Varga
Marie-Paule Sablin
Carlos Gomez-Roca
Nicolas Guilbaud
Aurelie Petain
Mariya Pavlyuk
Jean-Pierre Delord
PHASE I STUDIES
Purpose To determine the maximum tolerated dose (MTD) of F14512, a topoisomerase II inhibitor designed to target cancer cells through the polyamine transport system, (three-hour daily infusion given for 3 consecutive days every 3 weeks) in platinum-refractory or resistant ovarian cancer. Other objectives were safety, pharmacokinetics (PK), PK/pharmacodynamics relationship, and efficacy. Methods This was an open-label, dose-escalation, multicenter phase I study. Results Eleven patients were enrolled and were treated at dose levels (DLs) of 10 and 5 mg/m2/day. All patients received the 3 injections per cycle as per study protocol (median, 1 cycle (Ferlay et al. Int J Cancer 136:E359–386, 2015; Siegel et al. CA Cancer J Clin 65:5–29, 2015; Oronsky et al. Med Oncol 34:103, 2017; Barret et al. Cancer Res 68:9845–9853, 2008; Ballot et al. Apoptosis 17:364–376, 2012; Brel et al. Biochem Pharmacol 82:1843–1852, 2011; Gentry et al. Biochemistry 50:3240–3249, 2011; Kruczynski et al. Investig New Drugs 29:9–21, 2011; Chelouah et al. PLoS One 6:e23597, 2011)) with no dose reductions. At DL 10 mg/m2/day, 6 dose-limiting toxicities (DLTs) were reported (3/4 evaluable patients: 2 grade 3 febrile neutropenia, 1 grade 4 neutropenia lasting at least 7 days, 1 grade 3 nausea, 1 decreased appetite, and 1 grade 3 asthenia). At dose 5 mg/m2/day, 2 DLTs were reported (2/6 treated patients: 2 grade 3 febrile neutropenia). Both DLs were defined as MTD. Stable disease was reported as best overall response in 2 (40%) patients having both received 9 cycles, one at each DL. 90.9% of patients experienced grade 4 neutropenia, but for only one (9.1%) it was reported as a serious adverse event. Conclusion Although there was some encouraging efficacy signal, grade 4 neutropenia led to complications and it was decided to stop the study. A DL below 5 mg/m2/day was not tested as this would not allow reaching the minimum serum concentration needed for the pharmacological activity of the drug.
Ovarian cancer Dose-escalation F14512 Pharmacokinetics Safety Efficacy
The online version of this article ( https://doi.org/10.1007/s10637-018-0688-4) contains supplementary material, which is available to authorized users.
Ovarian cancer is the seventh most common malignancy and the second most common gynecological malignancy, accounting for approximately 239,000 newly diagnosed cases and 152,00 deaths worldwide [1]. In 2017, the number of newly diagnosed cases in the USA is estimated to be more than 22,000 and the number of deaths was expected to exceed 14,000 [2]. In Europe in 2012, an estimated 66,000 new cases of ovarian cancer were diagnosed, resulting in approximately 42,000 deaths [1]. The current standard of care for newly diagnosed ovarian cancer is debulking surgery, followed by carboplatin and paclitaxel chemotherapy. Despite approximately 80% response rates to primary therapy, over half of the patients relapse within 2 years and eventually develop platinum-resistant disease. Treatment options for platinum-resistant ovarian cancer (PROC) are clearly unsatisfactory, with response rates to paclitaxel or pegylated liposomal doxorubicin (PLD) ranging from 0%–30% and progression free survival of 2–6 months. [3]. Thus, there is an unmet clinical need to identify new therapeutic options for patients with PROC.
Vectorization can improve tumor selectivity of conventional cytotoxics by conjugating them with a chemical entity to target cancer cells more specifically. One strategy is to exploit a selective transport system, such as the polyamine transport system (PTS) which is overactive in many tumor cells. The anticancer drug candidate F14512 was designed to target cancer cells through the PTS. It contains a spermine chain in place of the C4 glyosidic moiety of etoposide. The positively charged spermine tail increases DNA binding to reinforce topoisomerase II (topo II) inhibition and favors the selective uptake of the drug by tumor cells via the PTS, resulting in decreased toxicity when used in vivo [4, 5, 6, 7, 8, 9, 10, 11]. In vitro, the superior anti-proliferative activity of F14512 was demonstrated in 21/29 human cancer cell lines [4]. In vivo, F14512 demonstrated antitumor efficacy in 13/19 experimental models used, yielding a response rate of 68%. In these models, complete tumor regression was observed after intravenous or oral administration of F14512 and antitumor activity was observed over a range of dose levels (DLs) providing evidence of its good tolerance [8].
The clinical efficacy of topo II inhibitors has been established in ovarian cancer [12, 13]. PTS activity in ovarian tumors was investigated and the differential uptake of F17073, a polyamine fluorescent probe acting as a biomarker of PTS activity, by ovarian cancer versus normal cells was demonstrated in 14/17 evaluable clinical samples analyzed ex vivo [14]. Preclinical studies using the SK-OV3 ovarian cancer cell line confirmed the high levels of PTS activity previously observed in patient samples. Indeed, a ten-fold increased sensitivity of SK-OV3 cancer cells to F14512 cytotoxicity compared to etoposide, a non-targeted topo II inhibitor, was observed [14]. Preliminary studies, which were performed in ovarian tumor models, such as the PTS(+) A2780R cisplatin-resistant cell line, confirmed the antitumor activity of F14512 and its potential as a new therapy for PROC [14].
The primary objective was to determine the maximum tolerated dose (MTD) of F14512 administered as a three-hour daily infusion given for 3 consecutive days (on days 1, 2, 3) every 3 weeks in women with platinum-refractory or resistant ovarian cancer. The secondary objectives were i) to assess the safety of F14512, ii) to characterize the pharmacokinetics (PK) and the PK/ pharmacodynamics (PD) relationship of F14512 and its metabolite F16490, iii) to assess the efficacy of F14512 according to Gynecologic Cancer Intergroup (GCIG) response criteria [15].
Patients and study design
Patients with histologically or cytologically confirmed advanced epithelial ovarian cancer, fallopian tube or peritoneal carcinoma considered platinum refractory or resistant, with no more than 2 prior platinum-based regimens, were eligible. Platinum-resistant disease was defined as progressive disease within 6 months of completing the most recent platinum-based regimen. Patient eligibility criteria are described in the Online Resource.
This was an open-label, dose-escalation, multicenter, phase I study (EudraCT Number: 2012–005798-29) conducted in 3 investigational sites in France. The 10 mg/m2/day dose of F14512 was planned as a starting dose (DL1) for escalation in cohorts of 3 to 6 patients until the MTD was reached. Dose escalation was based on a standard titration design by using increments of 33% except from the first dose escalation, which could proceed with a dose increment of 50% in the absence of grade 3 neutropenia and dose limiting toxicity (DLT) observed at DL1. Dose escalation then proceeded except if criteria of MTD were met at DL1. In that instance, the 5 mg/m2/day dose was tested. All patients in a DL had to be followed for at least 3 weeks (cycle 1) for DLT evaluation before the first patient of the next dose level started treatment. The final decision to proceed to the next DL was made by the safety committee at the dose-escalation meeting. The MTD was defined as the DL at which 2/3 or 2/6 patients experienced a DLT during the first cycle. The Recommended Dose (RD) was the DL immediately below the MTD. A total of 10 evaluable patients had to be treated at the RD.
Treatment could be continued until disease progression, unacceptable toxicity, patient's request to discontinue treatment or intercurrent illness which required treatment discontinuation in the investigator's opinion.
No routine premedication was recommended. However, magnesium supplementation could be needed from the first day of treatment with F14512 depending on serum magnesium values during the cycle.
F14512 was administered as three-hour daily infusion through a central venous catheter for 3 consecutive days every 3 weeks depending on recovery to normal hematopoiesis or recovery of non-hematological toxicities to grade 1. During the first cycle, G- and GM-CSF use was prohibited, however, there were no such constraints in subsequent cycles.
Criteria for evaluation
Toxicities were graded according to National Cancer Institute - Common Toxicity Criteria (NCI - CTC) for adverse events (AEs) (version 4.0). DLT determination criteria and safety assessments are described in the Online Resource. Response was assessed by using GCIG response criteria [15] incorporating RECIST version 1.1 and CA-125. Plasma PK assessments and statistical methods are described in the Online Resource.
A total of 11 patients were enrolled in the study and all were treated between June 2013 and May 2014. The patient baseline characteristics and demographics were comparable between the 2 DLs and are summarized in Table 1. Overall, patient median age was 63 (57.7–69.9) years while performance status was 0 in 36.4% of patients and 1 in 63.6% of patients. Median progression free interval was 0.4 months (0.0–7.7) and 36.4% of patients had ≥3 organs involved at baseline.
Baseline patient and disease characteristics
Dose level of F14512
10 mg/m2/day (n = 5)
5 mg/m2/day (n = 6)
Overall (n = 11)
[61.4–69.9]
Groups of age, N (%)
< 65
≥ 65
WHO performance status at baseline, N (%)
BSA (m2)
Primary tumor site
Peritoneal carcinoma
Histology, N (%)
Serous Carcinoma
Endometroid carcinoma
Histopathological grade, N (%)
G2 moderately differentiated
G2 poorly differentiated
Figo stage, N (%)
III B
III C
Time from first diagnosis to study entry (months)
[Range]
[9.7–25.4]
Progression free interval (months)
Number of organs involved, N (%)
1 organ
≥ 3 organs
Type of organs involved at baseline, N (%)
Peritoneum
Pleural effusion
BSA body surface area, WHO World Health Organization
Determination of MTD and DLTs
Five and 6 patients were treated with 10 mg/m2/day and 5 mg/m2/day, respectively, administered for 3 consecutive days, every 3 weeks. Patients received a median number of 1 cycle [1, 2, 3, 4, 5, 6, 7, 8, 9] and 1.5 cycles [1, 2, 3, 4, 5, 6, 7, 8, 9] at DL 10 mg/m2/day and DL 5 10 mg/m2/day, respectively. At DL 10 mg/m2/day, 6 DLTs were reported in 3/4 evaluable patients for MTD determination (Table 2). One patient was not evaluable because of incomplete cycle 1 due to a fatal unrelated AE (ischemic stroke). DLTs were hematological toxicities for 3 patients; 2 grade 3 febrile neutropenia and 1 grade 4 neutropenia lasting at least 7 days. Gastrointestinal toxicities of grade 3, which were DLTs, were reported in 1/3 patients (nausea, decreased appetite associated with grade 3 asthenia). Therefore, as per study protocol, dose was de-escalated to 5 mg/m2/day. At dose 5 mg/m2/day, 2 DLTs were reported in 2/6 treated patients. They were both hematological toxicities; 2 grade 3 febrile neutropenia. Permanent treatment discontinuation because of study drug-related toxicity was observed only at cycle 1 in 5 patients. All discontinuations were because of DLTs; 3 in patients treated at DL 10 mg/m2/day and 2 in patients treated at DL 5 mg/m2/day.
DLTs occuring in the dose-escalation phase
Dose of F14512 (mg/m2/day)
Treated/evaluable patients (N)
Patients with DLT (N)
Total cycles N (%)
Cycles administered median [range]
Type of DLTs (N)
13 (100.0)
1.0 [1.0–9.0]
Grade 3 Febrile neutropenia (2)
Grade 3 Nausea (1)
Grade 3 Asthenia (1)
Grade 3 Decreased appetite (1)
Grade 4 Neutropenia lasting at least 7 days (1)
Both DLs were defined as MTD because of DLTs observed.
A total of 29 cycles were administered, 13 at DL 10 mg/m2/day and 16 at DL 5 mg/m2/day. The first 3 patients received 10 mg/m2/day for 3 consecutive days. All patients received the 3 injections per cycle as planned by the study protocol. No dose reductions were reported.
All 11 patients were evaluable for safety. Hematological toxicities were mainly grade 4 neutropenia. They were experienced by 90.9% of treated patients and observed in 26/29 cycles administered. This neutropenia was reported as a serious drug-related AE in 1 patient (9.1%) only. Grade 3 febrile neutropenia was observed in 4 patients (36%), 2 at each DL. Neutropenic infection was observed in 1 patient at DL 5 mg/m2/day. Main non-hematological toxicities were general disorders reported in 9 patients (82%), experiencing mainly asthenia. Gastrointestinal disorders were reported in 6 patients (55%); nausea in 6 patients (55%) and vomiting in 4 patients (36%). Metabolism and nutrition disorder with decreased appetite in 5 patients (46%). Study drug-related AEs are summarized in Table 3. Study drug-related serious AEs (SAEs) were reported in 6 patients (55%); 3 patients at each DL and were hematological toxicities. Five of these 6 SAEs were DLTs; grade 3 febrile neutropenia was reported in 2 patients at each DL and grade 4 neutropenia lasting at least 7 days was reported in 1 patient at DL 10 mg/m2/day. There were no study drug-related deaths.
Grade 3–4 study drug-related adverse events (worse grade by patient)
System Organ Class
10 mg/m2/day
n = 5
5 mg/m2/day
n = 11
Any related TESS
Blood and lymphatic system disorders
Febrile neutropenia
Neutropenia
Stomatitis
General disorders and administration site conditions
Asthenia
Neutropenic infection
Musculoskeletal and connective tissue disorders
Myalgia
Dysgeusia
Confusional state
Skin and subcutaneous tissue disorders
Onycholysis
TESS treatment emergent signs and symptoms
Among the 11 patients treated, only 5 (45%) patients were evaluable for efficacy. Six (55%) patients were not evaluable because of premature discontinuation of study drug administration after cycle 1; DLT in 5/6 and treatment-unrelated toxicity for 1/6 patients. Among the 5 patients evaluable for efficacy, no objective response was observed. Only stable disease (SD) was reported as best overall response in 2 (40%) patients having both received 9 cycles, 1 at each DL.
Pharmacokinetics and pharmacodynamics
All 11 patients enrolled in the study were evaluable for PK and PD assessments. Two DLs, 5 mg/m2/day and 10 mg/m2/day, were tested. The PK profiles of F14512 and its metabolite F16490 were comparable between the 2 DLs. Concentrations of the BG metabolite were low and close to the lower limit of quantification. The inter-day reproducibility was evaluated for both metabolites and it is summarized in Table 4. No difference between Day 1 and Day 3 was observed. Because only 2 DLs were explored, no statistical analyses were performed to assess the dose proportional increase of AUCinf or Cmax. However, F14512 and F16490 dose dependent PK parameters increased with DL. For inter-day reproducibility, parameters were compared using a pairwise t-test or a Wilcoxon test (for AUCinf/dose of F14512) and no significant associations were found (Fig. 1a). There was also no significant difference between metabolite F16490 AUCinf/dose (Fig. 1b) and metabolic ratio (Fig. 1c) on day 1 and day 3. CA-125 and HE 4 were quantified at the end of each cycle in all patients enrolled in the study. Due to the low number of samples per patient, no association can be tested between biomarkers and efficacy.
Inter-day reproducibility of F14512 and its metabolite F16490
PK parameter
F14512 (n = 11)
Mean [range]
AUCinf/dose level
152 [67.7–308]
84.6 [41.3–136]
Cltot (L/h)
13.2 [6.17–22.4]
Metabolic ratio
0.580 [0.440–0.709]
Open image in new window
Comparison of F14512 AUCinf/dose level between day 1 and day 3 (a). Comparison of F16490 AUCinf/dose level between day 1 and day 3 (b). Comparison of F16490 metabolic ratio between day 1 and day 3 (c)
Despite good initial responses to frontline treatment with debulking surgery and platinum-based chemotherapy, most patients with advanced ovarian cancer relapse and ultimately succumb from platinum-resistant disease. There are currently no effective therapeutic options for patients with PROC and therefore, there is an urgent need for novel therapies. Topo II inhibitors are active drugs in ovarian cancer and PLD is a standard of care both in combination with carboplatin and as monotherapy. However, response rates to single-agent PLD in PROC remain modest at 5–10% [16].
This report details the results of a phase 1 study of F14512 in patients with platinum-refractory or resistant ovarian cancer. An escalating dose of F14512 was to be administered, starting from the dose of 10 mg/m2/day. However, the first 3 patients treated at dose level 10 mg/m2/day experienced a DLT. Therefore, the DL below, which was 5 mg/m2/day, was tested. Among the first 3 treated patients at DL 5 mg/m2/day, no DLT was observed. Three more patients were treated and 2 of them experienced a DLT. Thus, both DLs of 5 mg/m2/day and 10 mg/m2/day were defined as MTD. Although grade 4 neutropenia was experienced by 90.9% of all treated patients and observed in 26/29 cycles administered, it is of note that only for 1 patient this neutropenia was reported as a serious drug-related AE.
At DL 10 mg/m2/day, hematological toxicity (grade 4 neutropenia) was observed in all patients and in 12/13 cycles administered. At DL 5 mg/m2/day, hematological toxicity (grade 4 neutropenia) was also observed in all patients and in 14/16 cycles administered. For non-hematological toxicity, at DL 10 mg/m2/day the most common AEs observed were asthenia, decreased appetite and nausea. Of these, 1 nausea, 1 asthenia and 1 decreased appetite occurring at cycle 1 were grade 3 (DLTs). At dose level 5 mg/m2/day, the most common non-hematological toxicities observed were asthenia and nausea. Of these, 2 nausea, 2 asthenia and 2 decreased appetite were grade 3. SAEs were reported in 3 patients at each DL and were hematological toxicities. Of these, 5 were DLTs; grade 3 febrile neutropenia was reported in 2 patients at each DL and grade 4 neutropenia lasting at least 7 days was reported in 1 patient at DL 10 mg/m2/day. One grade 2 neutropenic infection was reported as SAE at DL 5 mg/m2/day, occurring at cycle 9. It should be stressed that during the first cycle, G- and GM-CSF use was prohibited.
Among the 5 patients evaluable for efficacy, no response was observed. Only SD was reported as best overall response in 2 patients having both received 9 cycles, 1 at each DL.
The PK profiles of F14512 and its metabolite F16490 in patients with ovarian cancer were comparable between DLs. Difference of PK parameters between Day 1 and Day 3 of both compounds were not statistically significant. The small number of DLs and patients did not allow statistical analysis of the linearity between DLs. However, the results suggested that the dose proportionality was respected. No reliable PK/PD analysis can be performed. It is of note that the higher grade of neutropenia, grade 4, was observed in the patient with the highest exposure to the compound.
F14512 has demonstrated promising activity in preclinical studies of both solid and hematological malignancies, including ovarian cancer [4, 10, 11, 14]. The first-in-man phase I study of F14512 as a single-agent in patients with relapsed or refractory acute myeloid leukemia (AML) demonstrated both minimal extramedullary toxicity and promising antileukemic activity, with complete remissions in 36% of patients at first relapse [17]. Based on its favorable safety profile and its promising antileukemic activity, F14512 is in further clinical investigation in patients with AML and it is currently being tested in a phase I-II study in combination with cytarabine.
In conclusion, F14512 infusion over 3 h administered for 3 consecutive days every 3 weeks at DLs of 10 mg/m2/day and 5 mg/m2/day, in platinum-resistant or refractory ovarian cancer, led to high incidence of grade 4 neutropenia reported in 90.9% of patients and in 89.7% of cycles administered. This grade 4 neutropenia led to a high rate of complications; febrile neutropenia was observed in 2 patients at each DL and neutropenic infection in 1 patient at DL 5 mg/m2/day. Therefore, it was decided to stop the study and a DL below 5 mg/m2/day was not tested. This was because a DL below 5 mg/m2/day did not allow reaching the concentration needed for the pharmacological activity of the drug. Given that predictable hematological toxicity has prevented adequate dose-escalation and the encouraging clinical efficacy demonstrated in AML, the addition of G-CSF to enable dose-escalation and full evaluation in ovarian cancer should be considered in case of further development.
We would like to thank investigators, patients and their families. The study was financially supported by Pierre Fabre Laboratoires (Toulouse, France). The authors acknowledge David Jegou for statistical assistance and Dr. George Xinarianos for editorial assistance in the preparation of this manuscript (on behalf of Gaea, Macclesfield, UK), funded by Pierre Fabre Laboratoires (Toulouse, France).
Funding for this study was provided by Pierre Fabre.
A.P, N.G., and M.P. report personal fees (employment at Institut de Recherche Pierre Fabre) during the conduct of the study. A.L reports grants from AZ, personal fees from AZ, grants from Gamamabs, personal fees from Gamamabs, grants from Clovis, personal fees from Clovis, grants from Roche, grants from Pharmamar, grants from Merus, grants from Pfizer, outside the submitted work. The remaining authors have nothing to disclose.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
ESM 1 (DOCX 20 kb)
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1.Gustave Roussy, Oncology DepartmentUniversité Paris-SaclayVillejuifFrance
2.INSERM U981VillejuifFrance
3.Department of Medical Oncology, Paris & Saint-CloudInstitut CurieParisFrance
4.INSERM U900 Research unitSaint-CloudFrance
5.Gustave Roussy Cancer Campus, Drug Development DepartmentVillejuifFrance
6.Institut Claudius Regaud, IUCT-Oncopole, Departement d'Oncologie MedicaleToulouseFrance
7.Institut de Recherche Pierre FabreToulouseFrance
Leary, A., Le Tourneau, C., Varga, A. et al. Invest New Drugs (2019) 37: 693. https://doi.org/10.1007/s10637-018-0688-4
Received 02 April 2018
Accepted 19 October 2018


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Sharing pictures of travels, nature, and such.
Yesterday, while hiking, I found myself noticing the uniqueness of the trees. None are exactly alike and I'm guessing there's a lesson in that somewhere.
An afternoon hike yesterday, led us to some beautiful puddles way back in the woods.


Weavly is an online site that allows you to create mashups of mixed video, Giffs and sounds. Create new video's from exhisting video's on YouTube, SoundCloud, and LoopCam. Imagine being able to create a new video for a lesson on Painting Landscapes using multiple existing video that's already available on YouTube. Using Weavly, you could combine Matisse, Van Gogh and Monet video clips all into one! Cool!